Search

Introduction: Clinical practice guidelines provide inconsistent recommendations regarding progestogen supplementation for threatened and recurrent miscarriage. We conducted a systematic review and meta-analysis to assess the effectiveness and safety of progestogens for these patients., Material and Methods: We searched Medline, Embase, and Cochrane Central Registry of Controlled Trials up to October 6, 2023 for randomized control trials (RCTs) comparing progestogen supplementation to placebo or no treatment for pregnant women with threatened or recurrent miscarriage. We assessed the risk of bias using a modified version of the Cochrane risk-of-bias tool and the certainty of evidence using the GRADE approach., Results: Of 15 RCTs (6616 pregnancies) reporting on threatened or recurrent miscarriage, 12 (5610 pregnancies) reported on threatened miscarriage with or without a prior history of miscarriage. Results indicated that progesterone probably increases live births (relative risk (RR) 1.04, 95% confidence interval (CI) 0.99-1.10, absolute increase 3.1%, moderate certainty). Of these RCTs, three (1973 pregnancies) reporting on threatened miscarriage with a prior history of miscarriage indicated that progesterone possibly increases live births (RR 1.06, 95% CI: 0.97-1.16, absolute increase 4.4%; low certainty), while four (2540 pregnancies) reporting on threatened miscarriage and no prior miscarriage left the effect very uncertain (RR 1.02, 95% CI: 0.96-1.10, absolute increase 1.7%; very low certainty). Three trials reporting on 1006 patients with a history of two or more prior miscarriages indicated progesterone probably increases live births (RR 1.08, 95% CI: 0.98-1.19, absolute increase 5.7%, moderate certainty). Six RCTs that reported on 2979 patients with at least one prior miscarriage indicated that progesterone probably increases live births (RR 1.07, 95% CI: 1.01-1.13, absolute increase 5.0%; moderate certainty). Progesterone probably has little or no effect on congenital anomalies (RR 1.06, 95% CI: 0.76-1.48, absolute increase 0.1%; moderate certainty), and other serious adverse pregnancy events (RR 1.07, 95% CI: 0.83-1.40, absolute increase 0.2%, moderate certainty)., Conclusions: In women at increased risk of pregnancy loss, progestogens probably increase live births without increasing adverse maternal and neonatal events. It remains possible that the benefit is restricted to those with prior miscarriages., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

A film composed of agarose and graphene (G) and magnetic nanoparticles (G-MNPs) is proposed as a sorbent for the extraction and determination of medroxyprogesterone (MED), levonorgestrel (LEV), norethisterone (NOR) and progesterone (PRO) in natural water samples. Both the preparation of the film and the extraction procedure were optimized. The optimal extraction parameters were as follows: isopropyl alcohol as activation solvent, sample pH value of 3.0, extraction time of 30 min, 1.00 mL of acetonitrile as eluent, elution time of 5 min and sample volume of 100.00 mL. HPLC with photodiode array detector was used for the separation and determination. The method presented a linear range between 2.50 and 75.0 μg L -1 for all analytes, and the LODs were between 1.40 and 1.80 μg L -1 . The method was applied to natural water samples, obtaining satisfactory recovery values (75-111 %). In conclusion, for the immobilization of the G-MNPs, agarose was used, which is a non-toxic, renewable and biodegradable material. The G-MNPs-agarose film was reused up to 70 times, without losing its extraction capacity significantly and presenting excellent sorbent properties, which allow the extraction and preconcentration of the progestogens under study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A variety of progestogens are widely used by women for contraception and menopausal hormone therapy. The progestogens undergo extensive metabolism by oral and parenteral routes of administration to form many metabolites. Although a small number of metabolites have been shown to be biologically active, most have not been tested for biologic activity. The present review shows that we know most about progesterone metabolism, followed by the metabolism of levonorgestrel and norethindrone. Very few studies have been carried out on metabolism of most of the progestogens. The clinical significance of this deficiency is that those progestogen metabolites that bind to the progesterone receptors may also bind to other steroid receptors and be responsible for some of the well-documented side effects of administered progestogens. We also discuss how obesity and genetic polymorphisms alter progestogen metabolism, and how development of oral progestogen formulations that are targeted to the colon, where the concentration of steroid-metabolizing enzymes is much lower than in the proximal gut, may have a beneficial effect on progestogen metabolism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Concerns are growing about adverse effects of progestins on biota, even at ultra-trace concentrations. The enrichment factor (EF) from extraction of analytes in environmental samples that is needed for sample pre-concentration can affect not only performance of the analytical method but also the matrix effect. Therefore, the present study aimed to assess the influence of high sample EF on performance of the high-performance liquid chromatography with atmospheric pressure chemical ionization and photoionization coupled with high-resolution mass spectrometry (HPLC-APCI/APPI-HRMS) method for analysis of progestins in waste water treatment plant (WWTP) effluents and surface waters and analysis of (anti-)progestogenic activities measured by (anti-)PR-CALUX bioassays. The results showed that HPLC-APCI/APPI-HRMS coupled with solid-phase extraction and a high EF (33,333 L water /L extract ) enabled the detection of more compounds compared to samples with lower sample EF (10,000 L water /L extract ). The matrix effect did not increase proportionally compared to lower EFs (10,000 and 16,666 L water /L extract ), and lower limits of quantification were achieved in WWTP effluents and surface waters. The results of bioassays have shown that relative EF of 25 L water /L bioassay appears high enough to detect progestogenic activity in treated waste water. Our study is one of the first to provide insights into sample pre-concentration in analysis of progestins and progestogenicity in aquatic environments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Menopausal women with an intact uterus choosing estrogens for menopausal symptom relief require a progestogen for endometrial protection. The aim of this systematic review was to evaluate the risks of endometrial hyperplasia resp. malignancy with different progestogens used in combined MHT. Overall, 84 RCTs were included. We found that 1) most studies were done with NETA, followed by MPA, MP and DYD and LNG, 2) most progestogens were only available as oral formulations, 3) the most frequently studied progestogens (oral MP, DYD, MPA, oral and transdermal NETA, transdermal LNG) were assessed in continuously as well as in sequentially combined MHT regimens, 4) FDA endometrial safety criteria were only fulfilled for some progestogen formulations, 5) most studies demonstrated endometrial protection for the progestogen dose and time period examined. However, 6) study quality varied which should be taken into account, when choosing a combined MHT, especially if off-label-use is chosen., Competing Interests: Declaration of Competing Interest Petra Stute has received honoraria for consultancies and/or presentations at conferences from Besins Healthcare, Theramex, Gedeon Richter, Exeltis, Jenapharm, Bayer, Hexal, Viatris and Vifor. No conflict of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users. Objective: To provide recommendations regarding COCs: formulations, use, efficacy, benefits and safety. Method: For these recommendations, we have used the modified Delphi methodology and carried out a systematic review of studies found in the literature and reviews performed in humans, published in English and Spanish in Pubmed, Medline and advanced medicine and computer networks until the year 2021, using the combination of terms: 'oral contraceptives', 'estroprogestins' and 'combined oral contraceptives'. Results: Regarding the estrogen component, initially switching from mestranol (the pro-drug of ethinylestradiol) to ethinylestradiol (EE) and then reducing the EE dose helped reduce side effects and associated adverse events. Natural estradiol and estradiol valerate are already available and represent a valid alternative to EE. The use of more potent 19-nortestosterone-derived progestins, in order to lower the dose and then the appearance of non-androgenic progestins with different endocrine and metabolic characteristics, has made it possible to individualize the prescription of COC according to the profile of each woman. Conclusion: Advances in the provision of new COCs have improved the risk/benefit ratio by increasing benefits and reducing risks. Currently, the challenge is to tailor contraceptives to individual needs in terms of safety, efficacy, and protection of female reproductive health.

Aim: This study aimed to investigate the real-world clinical practice of estrogen and progestogen prescriptions for menopausal women., Methods: Using a health care database in Japan, we conducted a cross-sectional study on estrogen prescriptions and detailed analyses of newly initiated estrogens and concomitant prescriptions of progestogens. Data between January 2005 and December 2021 were analyzed., Results: In 2021, the proportion of women aged 45-49 years receiving estrogens was 25.8 [95% confidence interval (CI): 25.3, 26.3] per 1000 women, while it was 6.4 [95% CI: 6.0, 6.7] for those aged ≥60 years. The prescription of estrogens gradually increased in women aged 50-59 years after 2009. In women without a history of hysterectomy, transdermal estradiol was the primary form of estrogens prescribed for ≥180 days, in women aged <60 years. The proportion of transdermal estradiol gradually increased each year, whereas that of oral-conjugated equine estrogens decreased. Among progestogen, the proportions of dydrogesterone and transdermal norethisterone acetate increased over time, while that of medroxyprogesterone acetate decreased. Approximately 30% of women prescribed estrogens for ≥180 days did not initiate progestogen concurrently. In women undergoing hysterectomy, progestogen was not initiated in >90% of cases, and transdermal estradiol was prescribed in approximately 80% of cases in 2021., Conclusions: This study reviewed the prescription of estrogens in menopausal women in Japan. A considerable number of women with a uterus are receiving estrogen therapy rather than estrogen-progestogen therapy (EPT), despite the guidelines recommending the use of EPT in these women., (© 2023 Japan Society of Obstetrics and Gynecology.)

Synthetic progestins are micropollutants of special concern, due to their growing use in human and veterinary therapies and their risks to aquatic life. Currently, there is a lack of environmental information on these compounds, worldwide. The main objective of this work was to characterize the levels of the most consumed progestins in Portugal. For that, Ria de Aveiro, Tagus estuary and Ria Formosa were sampled in a temporal perspective to evaluate levels of drospirenone (DRO), desogestrel (DSG), gestodene (GST) and levonorgestrel (LNG). Drospirenone and desogestrel were the most abundant progestins. In the North of Portugal, DSG was the most abundant (Aveiro: 193.9 ng L -1 in summer), while DRO was more representative in the South (Tagus: 178.9 ng L -1 ; Formosa: 125.7 ng L -1 ) and also in summer. These spatial differences can be associated with the hydrodynamics of each estuarine system as well as the distinct population and tourist levels associated with each site., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Patricia Cardoso reports financial support was provided by Foundation for Science and Technology. Hugo Morais reports financial support was provided by Foundation for Science and Technology. Patricia Cardoso reports financial support was provided by Ocean3R (NORTE-01-0145-FEDER-000064)., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Gestagens, a class of veterinary drugs also called progestogens, are synthetic hormones used to increase feed efficiency and rate of gain in heifers. The Canadian Food Inspection Agency analyzes progestogens melengestrol acetate (MGA), megestrol acetate, and chlormadinone acetate using liquid chromatography-mass spectrometry (LC-MS). Our conventional gestagen method for kidney fat has many time-consuming steps, including solid-phase extraction. A sample preparation procedure having fewer clean-up steps was developed for routine diagnostic analysis of kidney fat and provided similar results faster, and at lower cost. A confirmatory liver method for gestagens, developed using salt-assisted extraction, employed minimal clean-up steps that resulted in high chemical background at the desired lower limit of quantification (LLOQ). Differential ion mobility spectrometry, specifically high-field asymmetric waveform ion mobility spectrometry (FAIMS), was used to filter chemical background in the gas phase. The effect of the ionization probe position on FAIMS parameters, including sensitivity, is described. With LC-FAIMS-MS, chemical background for each gestagen was virtually eliminated, resulting in a quantitative liver method having the desired 0.6 ng/g LLOQ and estimated limits of detection (LODs) up to 140 times lower than LC-MS. Incurred MGA samples, analyzed using kidney fat and liver methods from the same animal, show levels within the quantitative ranges of both methods.

Progestogen administration is required to oppose naturally produced or administered estrogens to provide endometrial protection. Within HRT regimens, this should be delivered for at least the same duration as that produced during the luteal phase of the monthly cycle and in the recommended doses to protect against the risk of endometrial hyperplasia and endometrial cancer. This includes progestogens administered for 12-14 days a month in sequential regimens and continuous daily intake in continuous combined HRT regimens. Shorter durations and lower doses of progestogen intake are likely to be associated with an increased risk of breakthrough bleeding, endometrial hyperplasia, and endometrial cancer.

What Is Known and Objective: Approximately half of the patients with threatened miscarriage suffer an abortion, and consistent medication therapy to prevent threatened miscarriage is lacking. Our goal was to investigate the real-world pharmacological treatment patterns of patients with threatened miscarriage in China, with a focus on the trend and rationality of progestogen use over the last 7 years., Methods: We performed a cross-sectional analysis of data from the Hospital Prescription Analysis Cooperation Project that is overseen by the Chinese Pharmaceutical Association. Information was extracted from prescriptions of outpatients with threatened miscarriage between January 2014 and December 2020. We quantified the types of medications using the first level anatomical therapeutic chemical (ATC) classification code and the frequency of use of medicines classified as category X by the United States Food and Drug Administration (FDA). We also calculated the prevalence of the most frequently used progestogens by assessing prescription rates, determined the sum of the defined daily doses (DDDs) and defined daily cost (DDC) and evaluated the rationality of progestogens according to drug labels and guidelines., Results and Discussion: Of the 91,464 patients included in this study, 69.4% were from the eastern region, 92.5% were from tertiary hospitals, and 72.9% were between 25 and 34 years old. The average number of medications per patient was 1.4. The following types of medicines were the most prevalent: "genitourinary system and sex hormones" (90.7%), "alimentary tract and metabolism" (10.8%) and "blood and blood-forming organs" (9.9%). Progestogens were prescribed for 81,080 patients (88.6%), among which oral progesterone (39.7%) was the most commonly used, followed by oral dydrogesterone (34.4%), progesterone injection (26.0%), oral allylestrenol (0.7%) and progesterone gel (0.4%). In other words, 10,991 (12.0%) patients used more than one progestogen, and the top three combinations were oral dydrogesterone plus progesterone injection (5.6%), oral progesterone plus progesterone injection (4.7%) and oral dydrogesterone plus oral progesterone (1.1%). The prescription rate of dydrogesterone increased gradually, whereas that of progesterone, especially progesterone injection, obviously decreased. Among 34,760 prescriptions of progestogens with complete usage information, the primary errors of progestogen use were "low frequency" (18.4%), "high single dose" (15.9%) and "low single dose" (11.3%). In addition, 137 prescriptions were identified with drug-progestogen interactions, and 61 were identified with contraindications for progestogens. A total of 4.5% of prescriptions included FDA category X medicines., What Is New and Conclusion: Our findings are the first to provide information on medication use in patients with threatened miscarriage over the last seven years in China. Medicines targeting the "genitourinary system and sex hormones," especially progestogens, were the most commonly prescribed medications, among which dydrogesterone was the most prevalent. However, it is remarkable that the use of progestogens for the treatment of threatened abortion is still controversial; thus, high-quality large sample studies are still required, especially among Chinese patients. Since usage errors in progestogen records and exposure to category X medicines were common, more efforts are needed to guarantee the safety and rationality of medicines used in pregnant women., (© 2021 John Wiley & Sons Ltd.)

Objective: To compare the effectiveness of two different treatment regimens of dydrogesterone in the management of endometriosis-related chronic pelvic pain., Design: Observational, prospective cohort study over six months., Setting: Twenty gynecology clinics in the Russian Federation., Patient(s): Three hundred fifty women from 18 to 45 years of age with endometriosis and chronic pelvic pain with or without dysmenorrhea., Intervention(s): Dydrogesterone 10 mg 2 or 3 times daily, either between the 5th and 25th days of the menstrual cycle (prolonged cyclical treatment regimen) or continuously (continuous treatment regimen). For all patients, the data cutoff was at six months of treatment., Main Outcome Measure(s): Intensity of chronic pelvic pain on the 11-point numerical rating scale (after 6 months)., Result(s): A marked reduction in chronic pelvic pain was observed with both the prolonged cyclical and continuous treatment regimens (mean ± standard deviation change from baseline -3.3 ± 2.2 and -3.0 ± 2.2, respectively), with no significant difference between the two groups. With both regimens, patients experienced significant improvements in the intensity of chronic pelvic pain, number of days in which analgesics were required, severity of dysmenorrhea, sexual well-being, and health-related quality-of-life parameters. A favorable safety profile of dydrogesterone was confirmed, and no serious adverse drug reactions were reported during the study., Conclusion(s): Prolonged cyclical and continuous treatment regimens of dydrogesterone therapy both demonstrated a pronounced and similar reduction in the severity of chronic pelvic pain and dysmenorrhea and led to marked improvements in all study parameters related to quality of life and sexual well-being., Registration Number: NCT03690765., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Ovarian sex steroids can modulate new vessel formation and development, and the clarification of the underlying mechanism will provide insight into neovascularization-related physiological changes and pathological conditions. Unlike estrogen, which mainly promotes neovascularization through activating classic post-receptor signaling pathways, progesterone (P4) regulates a variety of downstream factors with angiogenic or antiangiogenic effects, exerting various influences on neovascularization. Furthermore, diverse progestins, the synthetic progesterone receptor (PR) agonists structurally related to P4, have been used in numerous studies, which could contribute to unequal actions. As a result, there have been many conflicting observations in the past, making it difficult for researchers to define the exact role of progestogens (PR agonists including naturally occurring P4 and synthetic progestins). This review summarizes available evidence for progestogen-mediated neovascularization under physiological and pathological circumstances, and attempts to elaborate their functional characteristics and regulatory patterns from a comprehensive perspective.

Hormone replacement therapy in menopause is used to improve climacteric syndrome in women whose quality of life is affected. However, given the wide variety of progestogens available, it is important to evaluate their differential benign changes (radiological, cellular, and clinical) on the breast. This review aimed to determine the different benign changes of progestogens used in postmenopausal combined hormone therapy on the breast (radiological, cellular, and clinical), in women without mammary pathology, in order to establish their safety profile. A systematic review of the literature was carried out with a balanced search strategy for the identification of relevant references in the MEDLINE, BVSalud, EMBASE, ProQuest, and Cochrane databases until November 2019. The search terms used were 'menopause' or 'hormonal replacement therapy' or 'progestins' or 'estrogen' or 'mastodynia' or 'benign breast disease' or 'mammography'. Data were collected from the 'eligible' articles by two researchers (ARF and SHA), and possible discrepancies in inclusion were resolved by consensus. A total of 1886 articles were identified; 60 full-text articles were reviewed, and 17 articles that met the inclusion criteria were included for the qualitative analysis. In conclusion, combined hormone replacement therapy is associated with benign effects on the breast, such as mastodynia and increased mammographic density.

This study evaluated reproductive indicators of gilts treated with altrenogest or an intravaginal device (IVD) containing medroxyprogesterone acetate (MPA) for estrous cycle synchronization, starting the protocol on different days of the estrous cycle or replacing the IVD in the middle of treatment. In Experiment 1, 126 gilts were assigned, according to the day of treatment onset (Day 5 or 10 of the estrous cycle), to the following treatments: Control-5 (no hormone); Control-10 (no hormone); IVD-5 (IVD with MPA); IVD-10 (IVD with MPA); ALT-5 (altrenogest); or ALT-10 (altrenogest). The first day of the previous estrus was considered as Day 0 of the estrous cycle, and progestogen groups were treated for 14 d. In Experiment 2, 63 gilts were assigned to Control, ALT, or IVD groups. Progestogen treatment started on Day 10 of the estrous cycle, and the IVD was replaced after 7 d of treatment. In both experiments, no gilts expressed estrus during progestogen administration. In Experiment 1, the interval hormonal withdrawal-to-estrus (IHE) tended to be shorter when treatment started on Day 10 than on Day 5 (3.6 vs. 4.1 d, respectively; P = 0.09). The percentage of gilts expressing estrus after hormone withdrawal was lower for IVD-gilts (76.3%) compared to ALT (100%) and Control-gilts (92.9%; P ≤ 0.07). The percentage of persistent follicles (PFOL) was greater in IVD-10 (60.0%) and ALT-10 (33.3%) than CONT-10 (0.0%; P ≤ 0.06). The adjusted farrowing rate (AFR) was lower in IVD (65.5%) and ALT (80.5%) compared with CONT (97.4%; P ≤ 0.08). In Experiment 2, the IHE was longer for ALT than IVD (4.9 vs. 3.9 d, respectively; P < 0.01). No difference among groups was observed in the percentage of gilts expressing estrus (overall 86.4%), but the occurrence of PFOL was higher in IVD (61.5%) compared to ALT (5.3%), and Control groups (10.5%; P < 0.01). The AFR was lower in IVD (53.8%) than in ALT (88.2%) and Control (94.7%; P ≤ 0.05). The total number of piglets born was not affected by hormonal treatments in either experiment. Estrous expression was delayed in gilts treated with altrenogest or IVD-MPA. However, the reproductive performance of IVD-gilts was compromised, which was not circumvented by IVD replacement in the middle of treatment. Therefore, further studies are necessary to understand MPA pharmacodynamics and investigate alternative devices for a steady release of progestogens in gilts., Competing Interests: Declaration of competing interests The authors declare no conflicts of interest. The funding sponsors had no role in the design of the study, collection, analyses, and interpretation of data, writing of the manuscript, and the decision to publish the results., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Natural progesterone (P4) has a unique pharmacodynamic activity and safety profile compared to the synthetic progestins. As a result, a class effect does not exist for both P4 and synthetic progestins, in terms of both their efficacy and safety. Progestogens act at the genomic level by binding to the nuclear receptors and modulating the expression of some target-genes. P4 and the synthetic progestins have a hugely variable affinity for binding not only to the P4 receptors but also to other members of the steroid receptor family including glucocorticoid receptor, androgen receptor and mineralocorticoid receptor. This leads to different and specific pharmacokinetic profiles, clinical pharmacodynamics, safety and efficacy. P4 produced in the luteal phase of the menstrual cycle has several physiological effects regulating menses and, in the pregnant uterus, controlling the development of endometrial receptivity preparing the endometrium for implantation. P4 and its associated metabolites are powerful biological agents through genomic action by the progesterone nuclear receptor with a finely tuned regulatory role throughout pregnancy, from conception until delivery. Extra-nuclear, non-classical mechanisms of action have also been identified, including steroid interactions with some membrane receptors [oxytocin receptors and γ-aminobutyric acid (GABA A ), and the induction of a direct relaxing effect on uterine contractility by blockage of calcium influx. The extent of activity of P4 on the central nervous system (CNS) is modulated by the route of administration: oral P4 is affected by the presence of bacteria and associated enzymes secreted in the gut, the intestinal wall and by the liver, whereas vaginal P4 is not. P4 and two important metabolites, namely, allopregnanolone (3a,5a-tetrahydroP4) and 3a,5a-tetrahydrodeoxycorticosterone, exert neuroprotective effects on neonates. They are also natural positive modulators of the neuronal GABA A receptor, providing a clear pathway to explain the rapid dose-dependent psychopharmacological actions including anxiolytic, antidepressant, anaesthetic, anticonvulsant and analgesic effects. Fundamental structural differences exist between P4 and the synthetic progestins, resulting in different safety profiles when they are used during the menstrual cycle, in early and late pregnancy and in the alleviation of peri- or postmenopausal symptoms., Competing Interests: Declaration of competing interest The author is a consultant at Besins Healthcare Global., (Copyright © 2020. Published by Elsevier Ltd.)

Progestational agents are often prescribed to increase the clinical pregnancy rate in assisted reproduction. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. Progesterone production from the corpus luteum is essential for reproduction, but assisted reproductive technologies (ART) can impair luteal function. ART cycles can be classified into three, fresh cycles in which there may or may not be luteal insufficiency, agonist or antagonist cycles in which there is luteal insufficiency, and luteal support is essential, and donor cycles, in which there is no corpus luteum, and a luteal phase has to be created. However, there is no adequate diagnostic test for luteal insufficiency. This article summarises the effect of various progestogens, progesterone itself whether administered vaginally, intra-muscularly, rectally or subcutaneously, and the effect of the progestogen, dydrogesterone. The time of commencement and cessation of therapy are also discussed. Progestogens are also often used to treat threatened and recurrent miscarriage. In these patients progestogen supplementation may need to be prolonged. In threatened miscarriage, until after all bleeding stops, and in recurrent miscarriage, at least as long as the luteo-placental shift., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Drospirenone (DRSP) was synthesized as an analogue of spironolactone with the aim of producing a fourth-generation progestogen that differed from earlier progestogens in that it had antiandrogenic and little or no androgenic activity and lacked estrogenic effects while retaining some antimineralocorticoid activity. Since then, DRSP has been included in several oral contraceptive preparations together with an estrogen. However, increasing evidence has demonstrated that DRSP 4 mg on its own inhibits ovulation. It was thus a logical development to determine the efficacy of a tablet that only included DRSP 4 mg as an oral contraceptive. This proved successful and this product has now been approved by the Food and Drug Administration (FDA)., (Copyright 2020 Clarivate Analytics.)

Object: Is it possible to use different progestins cotreatment with human menopausal gonadotrophin (hMG) in women with advanced endometriosis but normal ovulation during controlled ovarian hyperstimulation (COH) in vitro fertilization (IVF)? Whether different progestins treatments can be an alternative choice for women with severe endometriosis in considering IVF/ICSI treatment remains unknown? Design: Non-inferiority randomized clinical trial. Setting: Tertiary-care academic medical center. Population: Four hundred and fifty infertile patients with severe endometriosis undergoing IVF/ICSI between May 2016 and March 2017. Methods: Four hundred and fifty infertile patients with severe endometriosis undergoing IVF/ICSI were randomized to: medroxyprogesterone acetate +hMG; dydrogesterone +hMG; and progesterone +hMG. Ovulation was induced with a gonadotropin-releasing hormone agonist (GnRH-a) and chorionic gonadotropin (hCG). Viable embryos were cryopreserved for later transfer. Main Outcome Measures: The primary endpoint outcome was the number of oocytes retrieved. Secondary indicators included the incidence of a premature surge in luteinizing hormone (LH), the number of viable embryos, and clinical pregnancy outcomes. Results: The number of oocytes retrieved was higher in the medroxyprogesterone acetate +hMG group than the two other groups (9.3 ± 5.7 vs. 8.0 ± 4.5 vs. 7.8 ± 5.2, P = 0.021). LH levels were suppressed after a 6-day progestin treatment in the medroxyprogesterone acetate +hMG and dydrogesterone +hMG groups, but there was a rebound of LH values in the progesterone +hMG group. No premature LH surge and ovarian hyperstimulation syndrome (OHSS) occurred. No significant differences among the three groups were observed in fertilization and pregnancy outcomes. Conclusion: It is mandatory to point out that our conclusions are valid for patients with ovarian advanced endometriosis but normal ovarian functions. These results suggest three different progestins protocols are equivalent in terms of pregnancy outcomes for women with advanced endometriosis. PPOS protocol can be an alternative choice for women with severe endometriosis and normal ovarian reserve in IVF/ICSI treatment. These methods could be tested with other populations of women with endometriosis. Clinical Trial Registration: www.ClinicalTrials.gov, identifier:ChiCTR-OIN-16008529. Trial registration date: 2014-05-25. Date of first patient enrollment: May 2016., (Copyright © 2020 Guo, Li, Shen, Cong, Wang, Wu, Li, Gao, Ma, Zhang, Mao, Fu, Lyu, Chai and Kuang.)

Introduction: Progestogens are widely used for the conservative treatment of endometrial hyperplasia and early endometrial cancer. Nevertheless, they do not achieve the regression in all cases. Although several immunohistochemical markers have been assessed to predict the response to treatment, their usefulness is still unclear. We aimed to analyze the usefulness of each immunohistochemical marker studied in predicting the response to progestogens in endometrial hyperplasia and early endometrial cancer., Material and Methods: Electronic databases were searched for relevant articles from January 2000 to June 2018. All studies assessing the association of immunohistochemical markers with the outcome of the progestogen-based therapy in endometrial hyperplasia and early endometrial cancer were included. The expression of immunohistochemical markers in pretreatment phase and changes of expression during the follow-up were evaluated in relation to response to therapy and relapse., Results: Twenty-seven studies with 1360 women were included in the systematic review; 43 immunohistochemical markers were assessed. The most studied predictive markers in the pretreatment phase were progesterone and estrogen receptors, although with conflicting results; their isoforms, and in particular progesterone receptor B, appeared more promising. Further studies are needed to confirm the usefulness of mismatch repair proteins, Dusp6, GRP78 and PTEN combined with other molecules such as phospho-AKT or phospho-mTOR. In the follow-up phase, Nrf2 and survivin showed the stronger evidence; a role may also be played by Bcl2 and Ki67. Further studies are necessary for Fas, NCoR, AKR1C1, HE4, PAX2 and SPAG9., Conclusions: Several immunohistochemical markers might be helpful in predicting the response to conservative treatment of endometrial hyperplasia and early endometrial cancer on pretreatment and follow-up specimens. Further studies are needed to confirm their usefulness and possibly integrate them in a predictive immunohistochemical panel., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Evidence from different sources sustains a pro-oncogenic role of hormones, estrogens and progestogens, on the breast. The issue is of interest for young women, who are exposed to the hormonal changes imposed by the ovarian cycle and, often, take hormones with contraceptive purposes. Experimental and clinical studies show that both estrogens and progesterone are involved in mammary development during puberty and lactation, the changes being observed across mammalian species, including humans. Estrogen receptors, and more particularly the alpha isoform, participate in molecular processes of stem cells differentiation and epithelial proliferation through paracrine actions implicating growth factors. Progesterone also contributes through paracrine mechanisms involving one member of the tumor necrosis factor (TNF) family, the receptor activator of nuclear factor κB ligand (RANKL) and its receptor (RANK). Epidemiological studies have found that the length of the exposure to endogenous hormones, as determined by an early menarche or a late menopause, is a risk factor for breast cancer. Additional evidence has derived from studies with compounds modulating the estrogen or the progesterone receptors. Selective estrogen receptor modulators (SERM), like tamoxifen, have been shown to decrease the risk of breast cancer in both pre- and post-menopausal women. Aromatase inhibitors, which drastically reduce the levels of circulating estrogens, have reproduced the findings. The selective progesterone receptor modulators (SPRM) have been less investigated and issues concerning safety have arisen. These observations have interest for young women. High-risk women may consider the use of SERMs, for example, to reduce their risk. Much more common is the case of women who take hormones for contraception. The goal of the present article is twofold: i) to summarize the actual knowledge of the mechanisms implicating estrogens and progestogens on the risk for breast cancer and ii) to provide rationality for the debate about potential cancer risk of hormonal contraceptives, frequently used by premenopausal women., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective Data: Preterm prelabor rupture of membranes occurs in 3% of all pregnancies. Neonatal benefit is seen in uninfected women who do not deliver immediately after preterm prelabor rupture of membranes. The purpose of this study was to evaluate whether the administration of progestogens in singleton pregnancies prolongs pregnancy after preterm prelabor rupture of membranes., Study: Searches were performed in MEDLINE, OVID, Scopus, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of keywords and text words related to "progesterone," "progestogen," "prematurity," and "preterm premature rupture of membranes" from the inception of the databases until January 2018. We included all randomized controlled trials of singleton gestations after preterm prelabor rupture of membranes that were randomized to either progestogens or control (either placebo or no treatment). Exclusion criteria were trials that included women who had contraindications to expectant management after preterm prelabor rupture of membranes (ie, chorioamnionitis, severe preeclampsia, and nonreassuring fetal status) and trials on multiple gestations. We planned to include all progestogens, including but not limited to 17-α hydroxyprogesterone caproate, and natural progesterone., Study Appraisal and Synthesis Methods: The primary outcome was latency from randomization to delivery. Metaanalysis was performed with the use of the random effects model of DerSimonian and Laird to produce relative risk with 95% confidence interval. Analysis was performed for each mode of progestogen administration separately., Results: Six randomized controlled trials (n=545 participants) were included. Four of the included trials assessed the efficacy of 17-α hydroxyprogesterone caproate; 1 trial assessed rectal progestogen, and 1 trial had 3 arms that compared 17-α hydroxyprogesterone caproate, rectal progestogen, and placebo. The mean gestational age at time randomization was 26.9 weeks in the 17-α hydroxyprogesterone caproate group and 27.3 weeks in the control group. 17-α Hydroxyprogesterone caproate administration was not found to prolong the latency period between randomization and delivery (mean difference, 0.11 days; 95% confidence interval, -3.30 to 3.53). There were no differences in mean gestational age at delivery, mode of delivery, or maternal or neonatal outcomes between the 2 groups. Similarly, there was no difference in latency for those women who received rectal progesterone (mean difference, 4.00 days; 95% confidence interval, -0.72 to 8.72)., Conclusion: Progestogen administration does not prolong pregnancy in singleton gestations with preterm prelabor rupture of membranes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We systematically reviewed data about the effect of exogenous estrogens and progestogens on the course of migraine during reproductive age. Thereafter a consensus procedure among international experts was undertaken to develop statements to support clinical decision making, in terms of possible effects on migraine course of exogenous estrogens and progestogens and on possible treatment of headache associated with the use or with the withdrawal of hormones. Overall, quality of current evidence is low. Recommendations are provided for all the compounds with available evidence including the conventional 21/7 combined hormonal contraception, the desogestrel only oral pill, combined oral contraceptives with shortened pill-free interval, combined oral contraceptives with estradiol supplementation during the pill-free interval, extended regimen of combined hormonal contraceptive with pill or patch, combined hormonal contraceptive vaginal ring, transdermal estradiol supplementation with gel, transdermal estradiol supplementation with patch, subcutaneous estrogen implant with cyclical oral progestogen. As the quality of available data is poor, further research is needed on this topic to improve the knowledge about the use of estrogens and progestogens in women with migraine. There is a need for better management of headaches related to the use of hormones or their withdrawal.

Progestational agents are often prescribed to prevent pregnancy loss. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. Progestogens have therefore been used at all stages of pregnancy including luteal-phase support prior to pregnancy, threatened miscarriage, recurrent miscarriage, and to prevent preterm labor. In luteal support, a Cochrane review reported that progestogens were associated with a higher rate of live births or ongoing pregnancy in the progesterone group (odds ratio 1.77, 95% confidence interval (CI) 1.09-2.86). Evidence suggests that progestogens are also effective for treating threatened miscarriage. Again, in a Cochrane Database review, progestogens were associated with a reduced odds ratio of 0.53 (95% CI 0.35-0.79) when progestogens were used. In recurrent miscarriage, progestogens also seem to have a beneficial effect. A meta-analysis of progestational agents showed a 28% increase in the live birth rate (relative risk 0.72, 95% CI 0.53-0.97). For the last 30 years, progestogens have been used to prevent preterm labor. Recent meta-analyses also report beneficial effects. This review summarizes the literature and the author's experience using progestogens to prevent pregnancy loss.

Available medical treatments for symptomatic endometriosis act by inhibiting ovulation, reducing serum oestradiol levels, and suppressing uterine blood flows. For this, several drugs can be used with a similar magnitude of effect, in terms of pain relief, independently of the mechanism of action. Conversely, safety, tolerability, and cost differ. Medications for endometriosis can be categorized into low-cost drugs including oral contraceptives (OCs) and most progestogens, and high-cost drugs including dienogest and GnRH agonists. As the individual response to different drugs is variable, a stepwise approach is suggested, starting with OCs or low-cost progestogens, and stepping up to high-cost drugs only in case of inefficacy or intolerance. OCs may be used in women with dysmenorrhea as their main complaint, and when only superficial peritoneal implants or ovarian endometriomas <5 cm are present, while progestogens should be preferred in women with severe deep dyspareunia and when infiltrating lesions are identified., (Copyright © 2018. Published by Elsevier Ltd.)

Transdermal estradiol (TE) application (using gels, patches or a novel spray) is now a preferred route of hormone therapy (HT) in menopausal women, because various risks such as venous thromboembolism, stroke and unwanted hepatic effects can be reduced compared with oral HT. However, in the presence of an intact uterus, concurrent administration of progestogen is needed for endometrial protection. Due to the variety of progestogens available and differences in their clinical effects, the selection of the most appropriate substance and dosing for individual combination therapy can be difficult. This is especially true for TE gels and the novel spray because no fixed combination products are commercially available, meaning all progestogens must be added separately, and even for patches only two transdermal synthetic progestogens are available. The aim of this review was to summarize data on the endometrial effects of the different progestogens and to provide practical recommendations for the choice of progestogen (type and dosing), with a focus on endometrial protection when using TE, especially when using the novel estradiol (E2) spray.

Background: An indirect comparison meta-analysis published in 2013 reported that both vaginal progesterone and cerclage are equally efficacious for preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic short cervix. The efficacy of vaginal progesterone has been challenged after publication of the OPPTIMUM study. However, this has been resolved by an individual patient-data meta-analysis (Am J Obstet Gynecol. 2018;218:161-180)., Objective: To compare the efficacy of vaginal progesterone and cerclage in preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix., Data Sources: MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to March 2018); Cochrane databases, bibliographies, and conference proceedings., Study Eligibility Criteria: Randomized controlled trials comparing vaginal progesterone to placebo/no treatment or cerclage to no cerclage in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic cervical length <25 mm., Study Appraisal and Synthesis Methods: Updated systematic review and adjusted indirect comparison meta-analysis of vaginal progesterone vs cerclage using placebo/no cerclage as the common comparator. The primary outcomes were preterm birth <35 weeks of gestation and perinatal mortality. Pooled relative risks (RRs) with 95% confidence intervals were calculated., Results: Five trials comparing vaginal progesterone vs placebo (265 women) and 5 comparing cerclage vs no cerclage (504 women) were included. Vaginal progesterone, compared to placebo, significantly reduced the risk of preterm birth <35 and <32 weeks of gestation, composite perinatal morbidity/mortality, neonatal sepsis, composite neonatal morbidity, and admission to the neonatal intensive care unit (RRs from 0.29 to 0.68). Cerclage, compared to no cerclage, significantly decreased the risk of preterm birth <37, <35, <32, and <28 weeks of gestation, composite perinatal morbidity/mortality, and birthweight <1500 g (RRs from 0.64 to 0.70). Adjusted indirect comparison meta-analyses did not show statistically significant differences between vaginal progesterone and cerclage in the reduction of preterm birth or adverse perinatal outcomes., Conclusion: Vaginal progesterone and cerclage are equally effective for preventing preterm birth and improving perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix. The choice of treatment will depend on adverse events and cost-effectiveness of interventions and patient/physician's preferences., (Published by Elsevier Inc.)

Vast numbers of xenobiotics are known still to be present in treated municipal wastewater treatment plant (WWTP) effluents. Some of these possess endocrine-disrupting potency and pose risks for exposed aquatic animals. We searched for 17 potential environmental contaminants having affinity to the progesterone receptor. Relative potency values of these progesterone receptor-active chemicals were obtained. On the basis of relative potencies and measured environmental concentrations, the contribution of progestins to measured progestagenic activities was evaluated. Wastewaters (influent and effluent) and surrounding surface waters (upstream and downstream) at six municipal WWTPs were screened using instrumental chemical analysis and in vitro reporter gene bioassay. We showed the presence of target compounds and (anti-)progestagenic activities in municipal wastewater and surface water. Nine and seven progestins were identified in influent and effluent wastewaters, respectively. Only two compounds, progesterone and medroxyprogesterone were found in surface waters. Progestagenic agonistic activities in influents were partially masked by strong anti-progestagenic activities that were detected in all influents and ranged from 2.63 to 83 ng/L of mifepristone equivalents (EQs). Progestagenic activities were detected in all effluents and ranged from 0.06 to 0.47 ng/L of reference compound ORG 2058 EQs (a synthetic progestin equivalents), thus indicating incomplete removal of progestins during wastewater treatment processing. This activity poses a continuing risk for the aquatic environment. By contrast, anti-progestagenic activities showed better removal efficiency in WWTPs compared to progestagenic agonistic activities. Anti-progestagenic activities were found in only three of six effluents and ranged from 0.26 to 2.1 ng/L mifepristone EQs. We explained most of the progestagenic activity in municipal WWTP effluents by the presence of synthetic progestins and progesterone, which contributed 65-96% of such activity in samples where no antagonistic activity was found. The progestins medroxyprogesterone acetate, megestrol acetate and progesterone contributed most to the progestagenic activity detected in municipal effluents. Anti-progestagenic activities were found in some municipal effluents, but no causative agents were revealed because two analysed selective progesterone receptor modulators (SPRMs) with anti-progestagenic activities, mifepristone and ulipristal acetate, were not present in the effluents., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The efficacy of vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix has been questioned after publication of the OPPTIMUM study., Objective: To determine whether vaginal progesterone prevents preterm birth and improves perinatal outcomes in asymptomatic women with a singleton gestation and a midtrimester sonographic short cervix., Study Design: We searched MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to September 2017); Cochrane databases; bibliographies; and conference proceedings for randomized controlled trials comparing vaginal progesterone vs placebo/no treatment in women with a singleton gestation and a midtrimester sonographic cervical length ≤25 mm. This was a systematic review and meta-analysis of individual patient data. The primary outcome was preterm birth <33 weeks of gestation. Secondary outcomes included adverse perinatal outcomes and neurodevelopmental and health outcomes at 2 years of age. Individual patient data were analyzed using a 2-stage approach. Pooled relative risks with 95% confidence intervals were calculated. Quality of evidence was assessed using the GRADE methodology., Results: Data were available from 974 women (498 allocated to vaginal progesterone, 476 allocated to placebo) with a cervical length ≤25 mm participating in 5 high-quality trials. Vaginal progesterone was associated with a significant reduction in the risk of preterm birth <33 weeks of gestation (relative risk, 0.62; 95% confidence interval, 0.47-0.81; P = .0006; high-quality evidence). Moreover, vaginal progesterone significantly decreased the risk of preterm birth <36, <35, <34, <32, <30, and <28 weeks of gestation; spontaneous preterm birth <33 and <34 weeks of gestation; respiratory distress syndrome; composite neonatal morbidity and mortality; birthweight <1500 and <2500 g; and admission to the neonatal intensive care unit (relative risks from 0.47-0.82; high-quality evidence for all). There were 7 (1.4%) neonatal deaths in the vaginal progesterone group and 15 (3.2%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.18-1.07; P = .07; low-quality evidence). Maternal adverse events, congenital anomalies, and adverse neurodevelopmental and health outcomes at 2 years of age did not differ between groups., Conclusion: Vaginal progesterone decreases the risk of preterm birth and improves perinatal outcomes in singleton gestations with a midtrimester sonographic short cervix, without any demonstrable deleterious effects on childhood neurodevelopment., (Published by Elsevier Inc.)

Background: The progestogen 17-α hydroxyprogesterone caproate (17-OHPC) is 1 of only 2 agents recommended for clinical use in the prevention of spontaneous preterm delivery, and studies of its efficacy have been conflicting. We have developed an in-vitro model to study the fetal membrane weakening process that leads to rupture in preterm premature rupture of the fetal membranes (pPROM). Inflammation/infection associated with tumor necrosis factor-α (TNF-α) induction and decidual bleeding/abruption associated thrombin release are leading causes of preterm premature rupture of the fetal membranes. Both agents (TNF-α and thrombin) cause fetal membrane weakening in the model system. Furthermore, granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical intermediate for both TNF-α and thrombin-induced fetal membrane weakening. In a previous report, we demonstrated that 3 progestogens, progesterone, 17-alpha hydroxyprogesterone (17-OHP), and medroxyprogesterone acetate (MPA), each inhibit both TNF-α- and thrombin-induced fetal membrane weakening at 2 distinct points of the fetal membrane weakening pathway. Each block both the production of and the downstream action of the critical intermediate granulocyte-macrophage colony-stimulating factor., Objective: The objective of the study was to characterize the inhibitory effects of 17-OHPC on TNF-α- and thrombin-induced fetal membrane weakening in vitro., Study Design: Full-thickness human fetal membrane fragments from uncomplicated term repeat cesarean deliveries were mounted in 2.5 cm Transwell inserts and cultured with/without 17-alpha hydroxyprogesterone caproate (10 -9 to 10 -7 M). After 24 hours, medium (supernatant) was removed and replaced with/without the addition of tumor necrosis factor-alpha (20 ng/mL) or thrombin (10 U/mL) or granulocyte-macrophage colony-stimulating factor (200 ng/mL). After 48 hours of culture, medium from the maternal side compartment of the model was assayed for granulocyte-macrophage colony-stimulating factor and the fetal membrane fragments were rupture strength tested., Results: Tumor necrosis factor-alpha and thrombin both weakened fetal membranes (43% and 62%, respectively) and increased granulocyte-macrophage colony-stimulating factor levels (3.7- and 5.9-fold, respectively). Pretreatment with 17-alpha hydroxyprogesterone caproate inhibited both tumor necrosis factor-alpha- and thrombin-induced fetal membrane weakening and concomitantly inhibited the induced increase in granulocyte-macrophage colony-stimulating factor in a concentration-dependent manner. However, contrary to our prior reports regarding progesterone and other progestogens, 17-alpha hydroxyprogesterone caproate did not also inhibit granulocyte-macrophage colony-stimulating factor-induced fetal membrane weakening., Conclusion: 17-Alpha hydroxyprogesterone caproate blocks tumor necrosis factor-alpha- and thrombin-induced fetal membrane weakening by inhibiting the production of granulocyte-macrophage colony-stimulating factor. However, 17-alpha hydroxyprogesterone caproate did not also inhibit granulocyte-macrophage colony-stimulating factor-induced weakening. We speculate that progestogens other than 17-alpha hydroxyprogesterone caproate may be more efficacious in preventing preterm premature rupture of the fetal membranes-related spontaneous preterm birth., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In our previous study, we measured 0.23-13.67ng/L progestogens (progesterone, drospirenone, levonorgestrel) in natural waters in the catchment area of the largest shallow lake of Central Europe, Lake Balaton. Progestogen contaminations act as potent steroids with mixed progestagenic, androgenic and mild estrogenic effects that is why our aim was to investigate the morphological and molecular effects of mixture of progesterone, drospirenone, and levonorgestrel in environmentally relevant (10ng/L) and higher (50 and 500ng/L) exposure concentrations in common roach, Rutilus rutilus. Steroids (e.g. progestogens) and the protein deglycase DJ-1 chaperon molecule aim the same target molecules in cells, therefore, we hypothesized that a relationship may exist between progestogens and DJ-1. Furthermore, our other aim was to follow the changes of signal molecules of different biological function due to progestogen treatment in serum and brain. Adult roaches were exposed to 10, 50 and 500ng/L of mixture of progestogen for 42 days and their somatic indices (brain-somatic, liver-somatic, gonadosomatic and kidney-somatic) were measured. Vitellogenin (VTG) expression (estrogen effect) or inhibition (androgen effect) in fish is a widely used biomarker so we measured its changes in liver by ELISA. To determine the quantity and to map the spatial distribution of DJ-1 chaperon protein the brain and liver tissues were analyzed by ELISA and immunohistochemistry. Furthermore, we also studied molecular alterations: a) in the serum by measuring cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride concentrations and b) in brain homogenate using a cell stress array kit (26 protein). The somatic index of liver and kidney significantly in all the treated groups, whereas the gonadosomatic index of 500ng/L treated group showed significant decrease compared to control animals. VTG level increased significantly in 500ng/L progestogen treated group. Since the concentration of DJ-1 significantly increased in brain and liver in all progestogen treatment groups, the DJ-1 protein could be able to a more sensitive marker than VTG. Serum LDL and cholesterol levels of exposed fish were significantly decreased. DJ-1 was mediated through the stimulation of the expression of LDL-receptor which facilitates reuptake subsequently. In summary, our observations unfolded new data about molecular alterations induced by the combined action of environmental progestogens. In addition, the DJ-1 chaperon protein as a possible biomarker helped to trace the abiotic chemical environmental contaminations, like progestogens in the freshwater ecosystems., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This work describes the development and validation of a method for the simultaneous determination of 13 estrogens and progestogens in honey by high performance liquid chromatography-tandem mass spectrometry. The hormones were preconcentrated by solid phase extraction. Pretreatment variables were optimized for a better compatibility with electrospray ionization interfaced mass spectrometry. The analytes were analyzed in multiple-reaction monitoring mode with two pairs of precursor product ion transitions. The proposed method was validated with method detection limits of 0.01-0.33ng/g and good linearities (r 2 >0.9901) throughout the studied concentration range. The recoveries of analytes at the spiking levels (5ng/g and 25ng/g) ranged from 71.2% to 99.7%, with relative standard deviations below 20%. The method was used to determine the target compounds in honey samples (orange blossom, clover and multiflower) obtained from supermarkets. Two samples of honey were found to contain trace amounts of estrone (

Introduction: Today, it is a mandatory practice to prescribe a combination of estrogens and progestogens for menopausal women requiring hormone therapy and with a uterus. The WHI study and its reanalysis demonstrate a big difference in results between the conjugated equin estrogen (CEE) only vs.CEE plus medroxyprogesterone acetate (MPA) arms in relation with breast cancer and cardiovascular risk. The conclusion is that risk is clearly higher in the arm with MPA than in the CEE only arm. Although the only progestogen used in the WHI study was medroxyprogesterone acetate, side effects and intolerance have been extrapolated as a class effect to all progestogens. Areas covered: Progestogen tolerance and side effects in hormone therapy were reviewed. For that purpose, a limited literature search was conducted on key resources including Pubmed, the Cochrane Library, ECRI, and major international health technology agencies. Expert opinion: Many of the tolerance effects are based on limited data. There are no double-blind randomized trials comparing long-term safety for breast cancer and cardiovascular risk among different progestogens. Short-term clinical studies, observational, and in animal and in vitro studies indicate that both micronized progesterone and dydrogesterone are the safer progestogens with an acceptable metabolic profile.

Background: Postpartum women need effective contraception. Concerns have been raised that use of progestogen-only contraceptives (POCs) may affect breastfeeding performance and infant health outcomes., Objectives: We investigated the clinical outcomes of breastfeeding duration, initiation of supplemental feeding and weaning, as well as infant outcomes including infant growth, health and development among breastfeeding women using POCs compared with breastfeeding women not using POCs., Search Strategy: We searched the PubMed database for all articles published from database inception through December 2014., Selection Criteria: We included primary research studies of breastfeeding women of any age or parity who received POCs, including progestogen-only pills, injectables, implants or hormonal intrauterine devices (IUDs). The main outcomes were breastfeeding performance (as measured by initiation, continuation, frequency and exclusivity of breastfeeding) and infant health (as measured by growth, development or adverse health effects)., Results: Forty-nine articles reporting on 47 different studies were identified that investigated the use of POCs in breastfeeding women and reported clinically relevant outcomes of infant growth, health or breastfeeding performance. Studies ranged from poor to fair methodological quality and generally failed to show negative effects of the use of POCs on breastfeeding outcomes or on infant growth or development. One randomized controlled trial (RCT) raises concerns that immediate insertion of the levonorgestrel IUD postpartum may be associated with poorer breastfeeding performance when compared with delayed insertion, although two other RCTs evaluating early etonogestrel implants compared with delayed initiation of implants or depot medroxyprogesterone acetate failed to find such an association., Conclusion: The preponderance of evidence fails to demonstrate adverse breastfeeding outcomes or negative health outcomes in infants such as restricted growth, health problems or impaired development. Evidence newly added to this review was largely consistent with previous evidence., (Copyright © 2016. Published by Elsevier Inc.)

Objective: To evaluate the efficacy of vaginal progesterone administration for preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton gestation and a mid-trimester sonographic cervical length (CL) ≤ 25 mm., Methods: This was an updated systematic review and meta-analysis of randomized controlled trials comparing the use of vaginal progesterone to placebo/no treatment in women with a singleton gestation and a mid-trimester sonographic CL ≤ 25 mm. Electronic databases, from their inception to May 2016, bibliographies and conference proceedings were searched. The primary outcome measure was preterm birth ≤ 34 weeks of gestation or fetal death. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated., Results: Five trials involving 974 women were included. A meta-analysis, including data from the OPPTIMUM study, showed that vaginal progesterone significantly decreased the risk of preterm birth ≤ 34 weeks of gestation or fetal death compared to placebo (18.1% vs 27.5%; RR, 0.66 (95% CI, 0.52-0.83); P = 0.0005; five studies; 974 women). Meta-analyses of data from four trials (723 women) showed that vaginal progesterone administration was associated with a statistically significant reduction in the risk of preterm birth occurring at < 28 to < 36 gestational weeks (RRs from 0.51 to 0.79), respiratory distress syndrome (RR, 0.47 (95% CI, 0.27-0.81)), composite neonatal morbidity and mortality (RR, 0.59 (95% CI, 0.38-0.91)), birth weight < 1500 g (RR, 0.52 (95% CI, 0.34-0.81)) and admission to the neonatal intensive care unit (RR, 0.67 (95% CI, 0.50-0.91)). There were no significant differences in neurodevelopmental outcomes at 2 years of age between the vaginal progesterone and placebo groups., Conclusion: This updated systematic review and meta-analysis reaffirms that vaginal progesterone reduces the risk of preterm birth and neonatal morbidity and mortality in women with a singleton gestation and a mid-trimester CL ≤ 25 mm, without any deleterious effects on neurodevelopmental outcome. Clinicians should continue to perform universal transvaginal CL screening at 18-24 weeks of gestation in women with a singleton gestation and to offer vaginal progesterone to those with a CL ≤ 25 mm. Published 2016. This article is a U.S. Government work and is in the public domain in the USA., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA.)

Synthetic and natural steroid hormones have attracted some attention in recent years as endocrine active substances (EAS) that interact or interfere with the endocrine system. Endogenous hormones occur naturally in food of animal origin, among which bovine milk represents an important source. This study was conducted to determine the occurrence of steroid hormones (oestrogens, androgens, progestogens and glucocorticoids) in cow's milk samples from three farms in Switzerland. An isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of 12 hormones in milk. Some hormonal levels from individual cows showed large variations. The average levels of the hormones analysed (17α-estradiol = 31 ng kg(-)(1), 17β-estradiol = 6 ng kg(-)(1), estrone = 159 ng kg(-)(1), 4-androstenedione = 684 ng kg(-)(1), progesterone = 15486 ng kg(-)(1), 17-hydroxyprogesterone = 214 ng kg(-)(1), cortisone = 112 ng kg(-)(1), and cortisol = 235 ng kg(-)(1)) were comparable with literature data. Estriol, testosterone and androstenediols were not detected at their respective limit of quantification. No significant differences of hormonal content among milk from cows at different lactation/calving numbers were evidenced, except for progesterone and 4-androstenedione. Due to confounding parameters linked to the physiological stage of the animal, like pregnancy and gestational stage (pregnancy trimester), the causal correlation between the variation of the levels for these two hormones and the lactation/calving number could not be unambiguously demonstrated.

Background: Preterm birth complicates almost all triplet pregnancies and no preventive strategy has proven effective., Objective: To determine, using individual patient data (IPD) meta-analysis, whether the outcome of triplet pregnancy is affected by prophylactic administration of 17-hydroxyprogesterone caproate (17OHPc)., Search Strategy: We searched literature databases, trial registries and references in published articles., Selection Criteria: Randomised controlled trials (RCTs) of progestogens versus control that included women with triplet pregnancies., Data Collection and Analysis: Investigators from identified RCTs collaborated on the protocol and contributed their IPD. The primary outcome was a composite measure of adverse perinatal outcome. The secondary outcome was the rate of birth before 32 weeks of gestation. Other pre-specified outcomes included randomisation-to-delivery interval and rates of birth at <24, <28 and <34 weeks of gestation., Main Results: Three RCTs of 17OHPc versus placebo included 232 mothers with triplet pregnancies and their 696 offspring. Risk-of-bias scores and between-study heterogeneity were low. Baseline characteristics were comparable between 17OHPc and placebo groups. The rate of the composite adverse perinatal outcome was similar among those treated with 17OHPc and those treated with placebo (34 and 35%, respectively; risk ratio [RR] 0.98, 95% confidence interval [95% CI] 0.79-1.2). The rate of birth at <32 weeks was also similar in the two groups (35 and 38%, respectively; RR 0.92, 95% CI 0.55-1.56). There were no significant between-group differences in perinatal mortality rate, randomisation-to-delivery interval, or other specified outcomes., Conclusion: Prophylactic 17OHPc given to mothers with triplet pregnancies had no significant impact on perinatal outcome or pregnancy duration., Tweetable Abstract: 17-Hydroxyprogesterone caproate had no significant impact on the outcome or duration of triplet pregnancy., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Androgens and progestogens are two important groups of endocrine disrupting compounds (EDCs) which are implicated to produce severe detrimental impact over aquatic biota, even at very low concentrations of ngL(-1). For this reason, one of the major challenges to analytical chemists is the development of sensitive and selective extraction processes which allow the rapid and green determination of these emerging pollutants at low concentrations in environmental samples. Fabric phase sorptive extraction is a new, highly sensitive, efficient and solvent minimized technique which combine the advantages of sol-gel derived microextraction sorbents and the rich surface chemistry of cellulose fabric substrate. This process has several advantages such as minimum usage of organic solvents, short extraction times, small sample volumes and high analyte preconcentration factors. In this study, an extraction method based on sorptive fabric phase coupled to ultra-high-performance liquid chromatography tandem mass spectrometry detection (FPSE-UHPLC-MS/MS) has been developed for the determination of four progestogens and six androgens in environmental and biological samples. All the parameters involved in the extraction, such as sample volume, extraction and desorption times, desorption solvent volume and sample pH values have been optimized. The developed method provides satisfactory limits of detection (between 1.7 and 264ngL(-1)), good recoveries and low relative standard deviations (below 10% in tap and osmosis water and below 20% in wastewater and urine). Subsequently, the method was used to analyse tap water, wastewater treated with different processing technologies and urine samples. The concentrations of the detected hormones ranged from 28.3 to 227.3 ngL(-1) in water samples and from 1.1 to 3.7μgL(-1) in urine samples., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Progestogens are the first drugs to demonstrate reproducibly a reduction in the rate of early preterm birth. The efficacy and safety of progestogens are related to individual pharmacologic properties of each drug within this class of medication and characteristics of the population that is treated. The synthetic 17-hydroxyprogesterone caproate and natural progesterone have been studied with the use of a prophylactic strategy in women with a history of preterm birth and in women with a multiple gestation. Evidence from a single large comparative efficacy trial suggests that vaginal natural progesterone is superior to 17-hydroxyprogesterone caproate as a prophylactic treatment in women with a history of mid-trimester preterm birth. Progestogen therapy is indicated for women with this highest risk profile based on evidence from 2 trials. A therapeutic approach based on the identification of a sonographic short cervix has been studied in several phase III trials. Independent phase III trials and an individual patient metaanalysis suggest that vaginal progesterone is efficacious and safe in women with a singleton and a short cervix. Two trials that tested 17-hydroxyprogesterone caproate in women with a short cervix showed no benefit. No consistent benefit for the prophylactic or therapeutic use of progestogens has been demonstrated in larger trials of women whose pregnancies were complicated by a multiple gestation (twins or triplets), preterm labor, or preterm rupture of membranes. Unfortunately, several large randomized trials in multiple gestations have identified harm related to 17-hydroxyprogesterone caproate exposure, and the synthetic drug is contraindicated in this population. The current body of evidence is evaluated by the Grading of Recommendations Assessment, Development, and Evaluation guidelines to derive the strength of recommendation in each of these populations. A large confirmatory trial that is testing 17-hydroxyprogesterone caproate exposure in women with a singleton pregnancy and a history of preterm birth is near completion. Additional study of the efficacy and safety of progestogens is suggested in well-selected populations based on the presence of biomarkers., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This article reviews the data supporting the role of receptor activator of the nuclear factor kappa (RANK) and its ligand, RANKL, in progestogen-induced breast cancer. Both experimental and clinical studies have been included. The expression of both RANK and RANKL has been described in epithelial cells of both mice and humans. Experiments of gain and loss of function in mice have shown that RANK/RANKL mediate alveologenesis during pregnancy or the estrous cycle. Moreover, the participation of the RANK/RANKL has been detected in models of breast carcinogenesis associated with progestogens-like medroxyprogesterone acetate. Recent clinical studies have found that the expression of RANK is associated with parameters of aggressiveness of the tumor.

We sought to evaluate the therapeutic efficacy of levonorgestrel-releasing intrauterine system (LNG-IUS) with oral progestins for treatment of non-atypical endometrial hyperplasia (EH). Searches were conducted on PubMed, SCOPUS, and CENTRAL databases to August 2014, and reference lists of relevant articles were screened. The search was limited to articles conducted on human beings and females. The PRISMA Statement was followed. Seven randomized controlled trials (n = 766 women) were included. Main outcome measures were the therapeutic effect rate (histological response) after 3, 6, 12, and 24 months of treatment; rate of irregular vaginal bleeding; and the hysterectomy rate per woman randomized. The Cochrane Collaboration risk of bias tool was used for quality assessment. Metaanalysis was performed with fixed effects model. LNG-IUS achieved a highly significant therapeutic response rate compared with oral progestins after 3 months of treatment (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.39-3.82; P = .001, 5 trials, I(2) = 0%, n = 376), after 6 months of treatment (OR, 3.16; 95% CI, 1.84-5.45; P < .00001, 4 trials, I(2) = 0%, n = 397), after 12 months of treatment (OR, 5.73; 95% CI, 2.67-12.33; P < .00001, 2 trials, I(2) = 0%, n = 224), and after 24 months of treatment (OR, 7.46; 95% CI, 2.55-21.78; P = .0002, 1 trial, n = 104). Subgroup analysis showed evidence of highly significant therapeutic response following LNG-IUS compared with oral progestins for non-atypical simple as well as complex EH (OR, 2.51; 95% CI, 1.14-5.53; P = .02, 6 trials, I(2) = 0%, n = 290; and OR, 3.31; 95% CI, 1.62-6.74; P = .001, 4 trials, I(2) = 0%, n = 216, respectively). Compared with oral progestins, LNG-IUS achieved significantly fewer hysterectomies (OR, 0.26; 95% CI, 0.15-0.45; P < .00001, 3 trials, n = 362, I² = 42%). No difference was observed in the rate of irregular vaginal bleeding between both groups (OR, 1.12; 95% CI, 0.54-2.32; P = .76, 2 trials, n = 207, I² = 77%). Funnel plot analysis was not performed because of the relatively small number of included studies. For treatment of non-atypical EH, LNG-IUS achieves higher therapeutic effect rates and lower hysterectomy rates than oral progestins and should be offered as an alternative to oral progestins in these cases., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This guideline has been developed based on studied and clinical investigations. Therefore, it appears to be appropriate to use all the available evidence, which are very encouraging, in a summarized form to propose guidelines by a group of European experts in order to give the gynecologists, obstetricians and reproductive medicine specialists have direction with regard to the prevention or treatment of miscarriage for the benefit of the endangered pregnancies. There are a number of statements, opinions and guidelines already published for this topic, which are not entirely in agreement.

Aim: To study the effects of estrogen therapy, alone or combined with progestogens, and of tibolone on the expression of proliferation and apoptosis markers in normal breast tissue., Methods: Thirty 250-day-old Wistar rats were castrated and 3 weeks later received one of the following treatments by gavage for 5 weeks: (1) estradiol benzoate; (2) estradiol benzoate + medroxyprogesterone acetate; (3) estradiol benzoate + norethisterone acetate; (4) estradiol benzoate + dydrogesterone; (5) tibolone; (6) placebo. Following treatment, the expression of proliferating cell nuclear antigen (PCNA) and caspase-3 was analyzed by quantitative immunohistochemistry in the breast tissue, and proliferation and apoptosis were analyzed semiquantitatively by microscopic imaging., Results: There was a statistically significant difference among the groups for PCNA, caspase-3 and the caspase-3 : PCNA ratio. Tibolone was associated with the lowest proliferative activity, followed by estradiol benzoate + dydrogesterone; however, estradiol benzoate + dydrogesterone showed the greatest rate of apoptosis., Conclusions: The various progestogens can have more or less proliferative and pro-apoptotic effects than estradiol alone. Among the treatment schemes analyzed, the estradiol + dydrogesterone combination resulted in a higher apoptosis rate in relation to the proliferation rate and tibolone was associated with the lowest proliferation.

Objective: To determine whether 17 alpha-hydroxyprogesterone caproate (17OHPC) prolongs gestation beyond 37 weeks of gestation (primary outcome) and reduces neonatal morbidity (secondary outcome) in twin pregnancy., Design: Randomised controlled double-blind clinical trial., Setting: Tertiary-care university medical centre., Population: Unselected women with twin pregnancies., Methods: Participants received weekly injections of 250 mg 17OHPC (n = 194) or placebo (n = 94), from 16-20 to 36 weeks of gestation. Randomisation was performed using the permuted-block randomisation method. Data were analysed on an intention-to-treat basis., Main Outcome Measure: Preterm birth (PTB) rate before 37 weeks of gestation., Results: There were no significant differences in the average gestational age at delivery, or in the rates of PTB before 37, 32, and 28 weeks of gestation, between the two groups. The proportion of very-low-birthweight neonates (<1500 g) was significantly lower in the 17OHPC group (7.6%) compared with placebo (14.3%) (relative risk, RR 0.5; 95% confidence interval, 95% CI 0.3-0.9; P = 0.01). Progestogen-treated neonates had a significantly lower composite neonatal morbidity (19.1%) compared with placebo (30.9%) (odds ratio, OR 0.53; 95% CI 0.31-0.90; P = 0.02), with significantly lower odds for respiratory distress syndrome (14.4 versus 23.4%; OR 0.55; 95% CI 0.31-0.98; P = 0.04), retinopathy of prematurity (1.1 versus 4.6%; OR 0.21; 95% CI 0.05-0.96; P = 0.04), and culture-confirmed sepsis (3.4 versus 12.8%; OR 0.24; 95% CI 0.10-0.57; P = 0.00)., Conclusions: Intramuscular 17OHPC therapy did not reduce PTB before 37 weeks of gestation in unselected twin pregnancies. Nonetheless, 17OHPC significantly reduced neonatal morbidity parameters and increased birthweight., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Synthetic progestogens represent a class of pharmaceuticals widely used in oral contraceptives and in hormone replacement therapies. They reach the aquatic environment through wastewater effluents; however, environmental concentrations and effects on non-target organisms are poorly known. Given the important role of progestogens regulating fish spawning processes, this study aimed at assessing the in vitro interference of four currently used progestogens-drospirenone (DRO), levonorgestrel (LNG), norethindrone (NOR) and cyproterone acetate (CPA) - with key enzymatic activities involved in the synthesis of active steroids in carp (Cyprinus carpio). The enzymatic pathways investigated were (a) CYP17 (C17,20-lyase) and CYP11β involved in the synthesis of androgens, (b) CYP19 that catalyses the aromatization of androgens to estrogens, and (c) 20β-hydroxysteroid dehydrogenase (20β-HSD) responsible for the synthesis of maturation-inducing hormones. All tested progestogens significantly inhibited the synthesis of androgens: DRO (IC50: 3.8 μM) was the strongest inhibitor of CYP17 followed by CPA (IC50s: 183 μM). Moreover, NOR (IC50: 0.4 μM), DRO (IC50: 1.8 μM) and CPA (IC50s: 87 μM) inhibited CYP11β. An inhibition by NOR of ovarian CYP19 activity, and by DRO and CPA of 20β-HSD was also observed, but at rather high concentrations (500 μM). Overall, this study highlights the potential of synthetic progestogens, and particularly DRO and NOR, to interfere with the biosynthesis of androgens in carp gonads., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Progestin is a term used to describe a synthetic progestogen. The activity and potency of synthetic progestins are mostly evaluated via parameters associated with their endometrial effects, which are related to their interactions with progesterone, estrogen, androgen, glucocorticoid, and mineralocorticoid receptors. The chemical structure of progestins is the key to understanding their interactions with these receptors and predicting the other effects associated with these drugs. Due to their endometrial effect, progestins are used for different gynecological conditions, such as endometriosis, contraception, hormonal replacement therapy, and artificial reproduction techniques. This review is focused on improving our knowledge of progestins (from their history and biochemical effects related to their chemical structures to clinical applications in gynecological conditions) in order to improve clinical practice. [ABSTRACT FROM AUTHOR]

Background: Recurrent pregnancy loss (RPL) is defined as the loss of two or more pregnancies. Several treatment options are available, including progesterone, which is one of the few treatments that improve live birth rates in RPL patients. Objective: To compare the live birth rates, medical and obstetric characteristics, and RPL evaluation results of women with and without progesterone treatment. These women attended the RPL clinic at Soroka University Medical Center. Methods: A retrospective cohort study based on 866 patients was conducted. The patients were divided into two groups and examined: the dydrogesterone treatment group consisting of 509 women and a group of 357 patients who did not receive the treatment. All the patients had a subsequent (index) pregnancy. Results: The two groups were not statistically different in terms of their demographic and clinical characteristics or evaluation results. In a univariate analysis, no statistically significant differences were found between the groups in terms of live birth rates (80.6% vs. 84%; p-value = 0.209). In a multivariate logistic analysis adjusted for maternal age, the ratio of pregnancy losses to the number of pregnancies, other administered treatments, antiphospholipid syndrome, and body mass index, dydrogesterone treatment was found to be independently associated with a higher rate of live births than the control group (adjusted OR = 1.592; CI 95% 1.051–2.413; p-value = 0.028). Conclusions: Progesterone treatment is associated with an increased live birth rate in RPL patients. Studies with larger sample sizes are recommended to strengthen these results. [ABSTRACT FROM AUTHOR]

BACKGROUND: Preterm birth complicates almost all triplet pregnancies and no preventive strategy has proven effective. OBJECTIVE: To determine, using individual patient data (IPD) meta-analysis, whether the outcome of triplet pregnancy is affected by prophylactic administration of 17-hydroxyprogesterone caproate (17OHPc). SEARCH STRATEGY: We searched literature databases, trial registries and references in published articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) of progestogens versus control that included women with triplet pregnancies. DATA COLLECTION AND ANALYSIS: Investigators from identified RCTs collaborated on the protocol and contributed their IPD. The primary outcome was a composite measure of adverse perinatal outcome. The secondary outcome was the rate of birth before 32 weeks of gestation. Other pre-specified outcomes included randomisation-to-delivery interval and rates of birth at

Since the 1960s, contraceptive pills have been at the service of humanity. They are one of the innovations that have contributed the most to the changing role of women in society and to women achieving the role they play today. Combined oral contraceptives (COCs) opened up opportunities to increase knowledge about the effects of estrogens and progestins in the female organism. The overall results of this evolution were progestin-only contraceptives in general and estrogen-free oral contraceptives as progestin-only pills (POPs) in particular. To identify the position currently held by POPs, a bibliographic review was carried out in the following databases: PubMed, ScienceDirect, EBSCOhost, OvidSP, Embase, and SciELO in Spanish. POPs have evolved notably from restricted use only during breastfeeding to a broader context. The absence of estrogen in the pill currently offers more advantages than disadvantages. The recent introduction of POP containing 4.0 mg of drospirenone, administered in a 24/4-day regimen, offers better cycle control than previous POPs, as it allows much more predictable bleedings and the same contraceptive efficacy as COCs. Hormonal contraception use continues to grow. The options to regulate reproduction are numerous, and users have a greater number of options to choose the one that suits their needs and comforts. Health professionals must provide high-quality contraceptive counseling, offering all available tools, including POPs. [ABSTRACT FROM AUTHOR]