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To review the criteria for the selection of estrogens and especially progestogens for optimizing Menopausal Hormone Therapy (MHT). The main criteria are primarily derived from the Women's Health Initiative (WHI)-trial, disclosing the main risks like endometrial cancer, coronary heart disease (CHD), stroke, venous tromboembolism (VTE) and breast cancer. In addition observational studies must be considered for individualizing MHT, because WHI has tested only one preparation and has a lot of problems like early opening of the hormone/placebo-code (i.e., loss of placebo control), in 60% MHT-initiation too late, and in 40% risk factors for cardiovascular diseases and breast cancer. Pharmacological properties should be considered, such as only oral, but not transdermal estradiol increases VTE-risk. The choice of progestogens could be dependent on the different "partial effects" on steroid receptors, e.g., use of anti-androgenic progestogens in metabolic syndrome, Polycystic Ovary Syndrome (PCOS) etc., taking advantage of the anti-mineralocorticoid effect of drospirenone to stabilize blood pressure and reduce the risk of stroke, selection of tibolone for patients with sexual dysfunctions because its androgenic properties etc. Most important for the selection of the progestogen is endometrial efficacy, primary indication for progestogens in MHT. Therefore regular endometrial monitoring is reommended, using sequential or continuous combined regimens; "hormonal curettage" and/or the progestogen challenge text to avoid endometrial hyperproliferation. Levonorgestrel-IUD as progestogen component can reduce progestogen-dependent risks, offering also contraception, but often with longer bleeding problems, in contrast to sequential regimens of MHT, which can be used to treat irregular bleedings. Other main indications are treatment of climacteric complaints and prevention of osteoporosis and possible other preventive options. Regarding contraindications, according to the general rules of "class-labeling", they are the same for every MHT despite there are differences in benefits and risks. Choice of the timing of MHT-initiation is crucial to whether cardiovascular prevention (early start) or (like in WHI) increased risk of CHD and stroke occurs. The increased risk of breast cancer can be reduced using progesterone or its isomer dydrogesterone. Since, however, this risk cannot been excluded with any MHT, recommendations for screening on the possible development of breast cancer are given, on the basis of own recent research. Criteria for the selection of MHT are mainly to reduce possible risks as seen in WHI since for every MHT efficacy is good and essentially the same. Often the best choice is estradiol combined with progesterone or dydrogesterone, but also other progestogens should be considered including LNG-IUD, to optimize and individualize MHT. [ABSTRACT FROM AUTHOR]

The article discusses the issues of polypharmacy and unjustified prescribing in pregnant women. The author— Honoured Scientist of the Russian Federation, Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Full Professor, and Head of the Department for Obstetrics and Gynaecology with a Course on Perinatology at the Institute of Medicine of the Peoples’ Friendship University of Russia named after Patrice Lumumba, Viktor E. Radzinskiy — questions the established practice of unnecessary hospitalisation of pregnant women without clinical indications and prescribing them numerous medicinal products, including antimicrobials, hormones, and antispasmodics. In most cases, pregnancy does not require medical intervention. The widespread use of progestogens in patients with threatened miscarriage lacks an evidence base. Antispasmodics, such as papaverine, are ineffective in threatened preterm labour. The author calls for a rational approach to prescribing medicinal products to pregnant women based on current clinical practice guidelines and the “do no harm” maxim. Viktor E. RADZINSKIY emphasises the need to follow clinical protocols and ensure physicians are informed about the evidence for the use of medicinal products in pregnancy to prevent polypharmacy and adverse consequences.

5β-Cardenolides are pharmaceutically important metabolites from the specialized metabolism of Digitalis lanata. They were used over decades to treat cardiac insufficiency and supraventricular tachycardia. Since the 1960s, plant scientists have known that progesterone is an essential precursor of cardenolide formation. Therefore, biosynthesis of plant progesterone was mainly analyzed in species of the cardenolide-containing genus Digitalis during the following decades. Today, Digitalis enzymes catalyzing the main steps of progesterone biosynthesis are known. Most of them are found in a broad range of organisms. This review will summarize the findings of 60 years of research on plant progesterone metabolism with particular focus on the recent results in Digitalis lanata and other plants. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

INTRODUCTION. Polycystic ovary syndrome (PCOS) is the main cause of female infertility. Clinical practice guidelines on PCOS recommend combined oral contraceptives (COCs) as first-line therapy. Given the association of PCOS with a number of clinical conditions, including obesity, type 2 diabetes mellitus, metabolic syndrome, anxiety and depressive disorders, an increased risk of endometrial cancer, and cardiovascular diseases, it is important to describe and systematise data on the benefits and risks associated with COCs.AIM. This study aimed to review current data on the use of COCs in PCOS, focusing on the rationality of prescribing, the main risks of using COCs, and the measures to minimise these risks.DISCUSSION. Hirsutism is the most prominent clinical manifestation of hyperandrogenism; in PCOS, its prevalence is 65–75%. COCs containing progestins with anti-androgenic properties are effective in treating hirsutism and superior to anti-androgens alone. Women with PCOS are at increased risk of endometrial cancer due to prolongation of the oestrogen-dependent proliferative phase. This risk can be mitigated by the normalising effect of COCs on the menstrual cycle and the effect of the progestin component of COCs. This review highlights the controversial nature of data on the association of COCs with emerging or exacerbating mental disorders, impaired glucose tolerance, and arterial hypertension/other cardiovascular risks in PCOS. Since the main safety issue with COCs is their thrombogenicity, clinicians should take special care when prescribing medicinal products from this group to PCOS patients. Data on the effect of COCs on fertility in women with PCOS are limited, but there is published evidence of an adverse effect of long-term use of COCs on the results of assisted reproductive technologies.CONCLUSIONS. The key benefit of the non-contraceptive use of COCs in PCOS is in treating hyperandrogenism, mainly hirsutism. To achieve effect, the patient should take COCs containing progestins with anti-androgenic properties for at least 6 months. PCOS patients can also use COCs for contraception. Clinicians prescribing COCs to women with PCOS should consider the individual patient context, the aim of treatment, and any potential risks associated with COCs.

Endometriosis affects about 10% of women of reproductive age and can negatively impact their quality of life (QoL). Due to the heterogeneity of symptoms or even their absence, early diagnosis is difficult. Therefore, it is necessary to comprehensively assess the patient's complaints, including a thorough review of medical history, the results of imaging studies, and risk factors for endometriosis. Early diagnosis enables preemptive treatment and avoids surgical intervention. The article presents data on managing patients with endometriosis in outpatient settings, describing methods for non-invasive imaging diagnosis of endometriosis. Current options of pharmacotherapy aimed at controlling the development of the disease and improving the QoL of patients in the long term are addressed. Timely initiated drug treatment improves the QoL of patients, in some cases, leads to a regression of the lesions, and improves the prognosis for the reproductive function. A shift in focus to clinical diagnosis, combined with non-invasive imaging, shortens the time between the first consultation and the final diagnosis. According to the current view of Russian and international professional societies, therapy should be long-term; therefore, selecting treatment with predictable responses and monitoring the course of the disease is necessary.

A five-year-old female cat (Felis catus), of no specific breed, nulliparous, was referred to the JuliPet veterinary clinic in the municipality of Fortaleza-CE. The cat presented with an enlargement of the mammary chain, exhibiting ulcerated lesions with purulent exudation distributed bilaterally, with a history of contraceptive use. Histopathological analysis diagnosed the patient with feline mammary hyperplasia (FMH), a condition characterized by a rapid enlargement of one or more mammary glands and commonly associated with the use of exogenous progestogens. Consequently, performing ovariohysterectomy in young females prevents the occurrence of reproductive and mammary pathologies. The present study aims to describe the anesthetic protocol used for the surgical removal of the right and left mammary chains, along with the ulcerated tumor. [ABSTRACT FROM AUTHOR]

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 Lwater/Lextract) enabled the detection of more compounds compared to samples with lower sample EF (10,000 Lwater/Lextract). The matrix effect did not increase proportionally compared to lower EFs (10,000 and 16,666 Lwater/Lextract), and lower limits of quantification were achieved in WWTP effluents and surface waters. The results of bioassays have shown that relative EF of 25 Lwater/Lbioassay 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. [ABSTRACT FROM AUTHOR]

Hormone laboratories located "on-site" where field studies are being conducted have a number of advantages. On-site laboratories allow hormone analyses to proceed in near-real-time, minimize logistics of sample permits/shipping, contribute to in-country capacity-building, and (our focus here) facilitate cross-site collaboration through shared methods and a shared laboratory. Here we provide proof-of-concept that an on-site hormone laboratory (the Taboga Field Laboratory, located in the Taboga Forest Reserve, Costa Rica) can successfully run endocrine analyses in a remote location. Using fecal samples from wild white-faced capuchins (Cebus imitator) from three Costa Rican forests, we validate the extraction and analysis of four steroid hormones (glucocorticoids, testosterone, estradiol, progesterone) across six assays (DetectX® and ISWE, all from Arbor Assays). Additionally, as the first collaboration across three long-term, wild capuchin field sites (Lomas Barbudal, Santa Rosa, Taboga) involving local Costa Rican collaborators, this laboratory can serve as a future hub for collaborative exchange.

Endometriosis affects 10% of all women of reproductive age, i.e. 190 million patients. Ukraine currently does not gather statistics on the incidence of endometriosis, but, at a rough estimate, this number is approximately 280 thousand women and the real number may be higher. Endometriosis has known significant social, medical and economic impact. Therefore, Ukrainian leading specialists in obstetrics and gynecology focus on new treatments for endometriosis, given current scientific data and the needs of patients. The given resolution and algorithms for treatment for endometriosis are the common stand of leading specialists in gynecology in our country and were developed on the basis of modern domestic and foreign data and current clinical guidelines. This resolution aims to improve clinical approaches to the routine practice of treatment for endometriosis. The constant increase in the incidence of endometriosis and its management characteristics allows to conduct an extensive study of the effectiveness and safety profile of various progestogens. In recent years, a number of further evidence have appeared regarding dydrogesterone treatment for endometriosis. New data on the effectiveness of dydrogesterone offer another hormone-based treatment for endometriosis, which is extremely important given the need for long-term and individualized treatment for endometriosis. The Europ ean Society of Human Reproduction and Embryology (ESHRE) states that the degree of pain relief in endometriosis is the same for all hormone-based treatments, but the safety and tolerability profiles of different medicinal products differ, which must be considered. According to the obtained data on the effectiveness and metabolic safety profile of various progestogens and during the discussion, algorithms for dydrogesterone-based treatment for endometriosis were proposed.

According to consistent epidemiological data, the slope of the incidence curve of endometriosis rises rapidly and sharply around the age of 25 years. The delay in diagnosis is generally reported to be between 5 and 8 years in adult women, but it appears to be over 10 years in adolescents. If this is true, the actual onset of endometriosis in many young women would be chronologically placed in the early postmenarchal years. Ovulation and menstruation are inflammatory events that, when occurring repeatedly for years, may theoretically favour the early development of endometriosis and adenomyosis. Moreover, repeated acute dysmenorrhoea episodes after menarche may not only be an indicator of ensuing endometriosis or adenomyosis, but may also promote the transition from acute to chronic pelvic pain through central sensitization mechanisms, as well as the onset of chronic overlapping pain conditions. Therefore, secondary prevention aimed at reducing suffering, limiting lesion progression, and preserving future reproductive potential should be focused on the age group that could benefit most from the intervention, i.e. severely symptomatic adolescents. Early-onset endometriosis and adenomyosis should be promptly suspected even when physical and ultrasound findings are negative, and long-term ovulatory suppression may be established until conception seeking. As nowadays this could mean using hormonal therapies for several years, drug safety evaluation is crucial. In adolescents without recognized major contraindications to oestrogens, the use of very low-dose combined oral contraceptives is associated with a marginal increase in the individual absolute risk of thromboembolic events. Oral contraceptives containing oestradiol instead of ethinyl oestradiol may further limit such risk. Oral, subcutaneous, and intramuscular progestogens do not increase the thromboembolic risk, but may interfere with attainment of peak bone mass in young women. Levonorgestrel-releasing intra-uterine devices may be a safe alternative for adolescents, as amenorrhoea is frequently induced without suppression of the ovarian activity. With regard to oncological risk, the net effect of long-term oestrogen–progestogen combinations use is a small reduction in overall cancer risk. Whether surgery should be considered the first-line approach in young women with chronic pelvic pain symptoms seems questionable. Especially when large endometriomas or infiltrating lesions are not detected at pelvic imaging, laparoscopy should be reserved to adolescents who refuse hormonal treatments or in whom first-line medications are not effective, not tolerated, or contraindicated. Diagnostic and therapeutic algorithms, including self-reported outcome measures, for young individuals with a clinical suspicion of early-onset endometriosis or adenomyosis are proposed. [ABSTRACT FROM AUTHOR]

Objectives: The luteal phase supplementation (LPS) of the in vitro fertilization (IVF) cycle is crucial to increase the chance of a live birth. There is no preferred progestogen for use in the general population. The optimal progestogen regimen in the event of prior IVF failure is unknown. The aim was to compare the live birth rate for dydrogesterone plus progesterone gel versus aqueous progesterone plus progesterone gel in LPS of the IVF cycle in women with at least one previous IVF failure. Material and methods: A prospective randomized single-center study enrolled women with at least one previous IVF failure undergoing another IVF cycle. Women were randomly assigned in a 1:1 ratio to 2 arms depending on LPS protocol: dydrogesterone (Duphaston®) + progesterone in vaginal gel (Crinone®) vs aqueous progesterone solution in subcutaneous injection (Prolutex®) + progesterone in vaginal gel (Crinone®). All women underwent fresh embryo transfer. Results: The live birth rate with one prior IVF failure was 26.9% for D + PG vs 21.2% for AP + PG (p = 0.54), and with at least two IVF failures: 16% for D + PG vs 31.1% for AP + PG (p = 0.16). There were no significant differences in live birth rates between protocols, regardless of the number of prior IVF failures. Conclusions: In light of the evidence from this study that neither of the two LPS protocols is more effective in women with prior IVF failure, other factors, such as potential side effects, dosing convenience and patient preference, should be considered when choosing a treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Since the middle of the 20th century, synthetic sex hormones (estrogens and progestins) have been administered to millions of pregnant or not women worldwide, mainly to avoid miscarriage or for comfort, although their mode of action and their effects on the mother and fetus were ignored. Despite the alerts and the description of somatic and psychiatric disorders in children exposed in utero, synthetic estrogens were prohibited for pregnant women only in the 1970s and 1980s, but some progestins are still authorized. In this review, we summarize the psychiatric disorders described in children exposed in utero to such hormones, focusing particularly on schizophrenia, bipolar disorders, severe depression, eating disorders, suicide and suicide attempts. Moreover, only in 2017 the mechanism of action of these xenohormones has started to be deciphered. Some studies showed that in the fetus exposed in utero, they alter the DNA methylation profile (mainly hypermethylation), and consequently the expression of genes implicated in neurodevelopment and in regulating the sexual organ morphogenesis and also of the promoter of estrogen receptors, located in the amygdala. These deleterious effects may be transmitted also to the next generations, thus affecting the children directly exposed and also the following generations. [ABSTRACT FROM AUTHOR]

Miscarriage remains an important global problem: 23 million miscarriages are registered annually in the world, i.e. 44 pregnancy losses every minute, and the total risk of miscarriage is 15.3% of all pregnancies. Effective methods of pregnancy preservation (in case of idiopathic miscarriage and threatened miscarriage) include lifestyle modification and progestagen therapy. Progesterone is the main hormone necessary to maintain pregnancy. The effectiveness of progestogens among medical methods that increase the chances of pregnancy preservation has been proven by numerous studies. Effectiveness and safety of various types of progestogens during pregnancy have been studied. As a result, progesterone and dydrogesterone became the only progestogens approved for use in obstetrics – micronized progesterone and dydrogesterone reduce the frequency of miscarriage in women with clinical diagnoses of threatened miscarriage and idiopathic recurrent miscarriage. In addition, the progestogens safety has been carefully studied in modern randomized studies, prospective trials and meta-analyses and the same safety profile of dydrogesterone and micronized progesterone for pregnant women and the fetus has been proven. Studies have shown that oral dydrogesterone has relatively low antagonistic activity at glucocorticoid and mineralocorticoid receptors compared to progesterone and therefore well tolerated. Oral dydrogesterone due to the peculiarities of structure has improved bioavailability compared to progesterone, which allows a woman to avoid the inconvenience and discomfort associated with the intravaginal or intramuscular use of progesterone. In addition, dydrogesterone has a 1.5 times higher affinity for progesterone receptors compared to micronized progesterone and a pronounced anti-inflammatory and immunomodulation effect, which provides certain clinical advantages for patients after recurrent pregnancy losses. Thus, progestogens are indicated for all patients with recurrent pregnancy losses from the moment of receiving a positive pregnancy test, as they reduce the risk of miscarriage. It is important that the use of progestagen drugs during the first and second trimester of pregnancy is not associated with side effects

Since the middle of the 20th century, synthetic sex hormones (estrogens and progestins) have been administered to millions of pregnant or not women worldwide, mainly to avoid miscarriage or for comfort, although their mode of action and their effects on the mother and fetus were ignored. Despite the alerts and the description of somatic and psychiatric disorders in children exposed in utero, synthetic estrogens were prohibited for pregnant women only in the 1970s and 1980s, but some progestins are still authorized. In this review, we summarize the psychiatric disorders described in children exposed in utero to such hormones, focusing particularly on schizophrenia, bipolar disorders, severe depression, eating disorders, suicide and suicide attempts. Moreover, only in 2017 the mechanism of action of these xenohormones has started to be deciphered. Some studies showed that in the fetus exposed in utero, they alter the DNA methylation profile (mainly hypermethylation), and consequently the expression of genes implicated in neurodevelopment and in regulating the sexual organ morphogenesis and also of the promoter of estrogen receptors, located in the amygdala. These deleterious effects may be transmitted also to the next generations, thus affecting the children directly exposed and also the following generations.

The presence of endocrine-disrupting chemicals (EDCs) in aquatic environments such as water, sediment, and sludge received more and more attention. However, the bioaccumulate properties of EDCs, particularly progestins and androgens, in various tissues of different wild freshwater fish species, as well as their effects on human health, have not been fully studied. The muscle, liver, and gills of three wild fish species obtained from the East Dongting Lake in southern China were examined for the presence of 19 EDCs (4 progestins, 5 androgens, 6 estrogens, and 4 phenols). Seventeen analytes were detected in all fish samples, and the concentrations of progestins, androgens, estrogens, and phenols ranged from ND–78.80 ng/g (wet weight, ww), ND–50.40 ng/g ww, ND–3573.82 ng/g ww, and ND–88.17 ng/g ww, respectively. The bioaccumulation of some EDCs in wild fish from East Dongting Lake was species-specific. Additionally, AND, EES, P4, and E2 were discovered in the liver at higher levels than in the muscle, suggesting that livers had a larger ability for enriching these EDCs than the muscle. Furthermore, the relationships between the fish sizes and the EDC concentrations indicated that total weight and length had a negligible impact on the bioaccumulation of EDCs in various fish species. Most importantly, the effects of EDCs on human health as a result of fish consumption were assessed. Although the estimated daily intakes (EDIs) of most EDCs were much lower compared with the corresponding acceptable daily intakes (ADIs) via consuming fish collected in this study, the EDI of EE2 in Silurus asotus was higher than the ADI of E2, indicating that Silurus asotus from East Dongting Lake should be eaten in moderation by local residents. [ABSTRACT FROM AUTHOR]

Summary: Progestogens and androgens have been found in many plants, but little is known about their biosynthesis and the evolution of steroidogenesis in these organisms. Here, we show that the occurrence and biosynthesis of progestogens and androgens are conserved across the viridiplantae lineage.An UHPLC‐ESI‐MS/MS method allowed high‐throughput analysis of the occurrence and chemical conversion of progestogens and androgens in 41 species across the green plant lineage.Dehydroepiandrosterone, testosterone, and 5α‐dihydrotestosterone are plants' most abundant mammalian‐like steroids. Progestogens are converted into 17α‐hydroxyprogesterone and 5α‐pregnane‐3,20‐dione. Androgens are converted into testosterone and 5α‐dihydrotestosterone. 17,20‐Lyases, essential for converting progestogens to androgens, seem to be most effective in monocot species.Our data suggest that the occurrence of progestogens and androgens is highly conserved in plants, and their biosynthesis might favor a route using the Δ4 pathway. [ABSTRACT FROM AUTHOR]

Key content: Women receiving estrogen replacement require concomitant progestogen to prevent endometrial hyperplasia and carcinoma.A variety of progestogens are used in hormone replacement therapy (HRT), with different advantages and disadvantages and routes of administration.Progestogenic side effects may be mild but can be debilitating and lead to the discontinuation of HRT, so progestogens should be tailored to the individual woman.Combined HRT containing estrogen and progestogens may be associated with a small increase in the absolute risk of breast cancer, which is not seen in women taking estrogen alone. However, this risk is small, particularly when compared with other modifiable lifestyle risk factors.The addition of certain progestogens to estrogen in the long term may be associated with an increased risk of heart disease, breast cancer and dementia. Learning objectives: To understand relative advantages and disadvantages of the different progestogens, regimens and routes of administration.To be aware of current evidence for types, dose and routes of administration of different progestogens.To be able to prescribe progestogens safely in terms of side effect and risk profiles that are individualised to the patient. Ethical issues: Well‐informed counselling including absolute, individualised risks for women considering HRT with a progestogenic component is essential to allow patients to make well‐informed choices. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the application status and rationality of progestogens in outpatient and emergency patients in China based on big data analysis techniques, so as to provide support for promoting clinical rational drug use and ensuring drug safety for patients. METHODS: Data of progestogen prescriptions from 2016 to 2020 were extracted from 112 hospitals in 9 cities. The application status of progestogens in China was analyzed, the composition and selection of progestogen for typical diseases were analyzed, and the problem of off-label indications was discussed. RESULTS: Totally 540 184 prescriptions were enrolled, including 605 233 records of progestogens. Except for 2020, which may be affected by COVID-19, the overall use and frequency of progestogens were on the increase, and the defined daily cost of high-priced progestogens decreased significantly since 2017. Progestin and dydrogesterone were the most widely used, and the latter had an obvious trend of increasing in clinical selection. Drug combination of progestogens were common (10. 9%, 58 625 cases). The applications of progestogens in patients with typical diseases had their own characteristics, and the drug selection was basically rational. Off-label indications were also common, and the most common diagnoses were endometrial polyps, gynecological examination and vaginitis. CONCLUSIONS: Progestogens are widely used in China and show an increasing trend, and the clinical application is basically reasonable, yet the problem of off-label indication drug use and the lack of evidence for drug combination deserve attention. In the future, it is still necessary to carry out high-quality clinical studies with large samples to verify the safety, effectiveness and economy of the use of progestogens. [ABSTRACT FROM AUTHOR]

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]

The aim of the present study was to compare the effect of the administration of two types of progestagens (FGA or MPA), on fertility using protocols of different durations. Two experiments were conducted with a total of 69 multiparous ewes. Experiment 1. was conducted with 46 ewes aged 2-5 years from the North-Eastern Bulgarian thin fleece breed - Shumenski type. Four experimental groups were formed depending on the progestagen source and the time of the timed artificial insemination, after removing the vaginal sponges (FGA /48; FGA/42; MPA/48; MPA/42). The sponges stay for all groups was 12 days. At the time of removal of the sponges, 500 IU of PMSG was injected. Experiment 2. was conducted with 23 ewes aged 2-5 years from Synthetic population Bulgarian milk. Two experimental groups were formed depending on the progestagen source: MPA / FGA.The stay of sponges for all groups was 5 days. At the time of sponge removal, 400 IU of PMSG was injected. No significant differences were found in the values of the fertility results in the experimental groups in Experiment 1. The highest value of the fertility was in the sheep of group MPA / 42 hours - 58.33%, and the lowest value in FGA / 48 hours after sponge removal – 36.36%. In Experiment 2, fertility was also higher, but not statistically significant, in the MPA group was 54.55% versus 41.67% for the FGA group. [ABSTRACT FROM AUTHOR]

The menopause is a significant event in a women's life that can potentially impact on her quality of life in several ways. It marks the end of the reproductive life cycle and the clinical manifestations of the menopause result from the eventual exhaustion of oocytes within the ovaries. The depletion of these oocytes results in chronic hypoestrogenic state, which in the short term can cause menopausal symptoms and over a longer period, may impact upon bone and cardiovascular health. This review summarises current understanding of pathophysiology of the symptoms of the menopause as well as reviewing the current recommendations for HRT use in symptomatic menopausal women. The benefits of HRT in improving the symptoms of menopause are discussed as well as a review of the evidence pertaining to the potential risks associated with HRT. [ABSTRACT FROM AUTHOR]

Background: There has been a growing interest in alternatives to surgery for controlling reproduction in tom cats, and the resultant medical options add to a practitioner's toolbox when handling these cases in clinical practice. It is important, however, that when suggesting these drugs, veterinarians have a good understanding of their mode of action, and their correct use and dosage. Clinical relevance: Breeders increasingly wish to be able to switch on/off the reproductive ability of their tom cats in a controlled manner. In addition, in small animal medicine, there has been concern from some academics, and a growing number of pet cat owners, about potential long-term effects of surgical sterilisation. Further, for some cats surgical castration may not be possible due to health conditions that mean anaesthesia is unsafe. In all of these scenarios, medical alternatives to surgery can prove useful. Equipment and technical skills: No special equipment or technical skills are required. A good knowledge of the medical alternatives to surgical sterilisation for controlling reproduction in a tom, and making sure the patient is a suitable candidate, are, however, important for ensuring the cat's health during and after treatment and the owner's satisfaction. Audience: This review is aimed principally (but not exclusively) at veterinary practitioners working with cat breeders who seek a temporary arrest in their tom cat's reproduction. It may also help practitioners with clients who would like an alternative to surgery or with cats where anaesthesia for surgical castration is not possible. Evidence base: Advances in reproductive feline medicine have resulted in improved knowledge of medical contraception. This review draws on scientific evidence-based papers that report on the mode of action, length of efficacy and potential side effects of different methods of medical contraception, as well as the authors' own clinical experience. [ABSTRACT FROM AUTHOR]

Background: For the development of PGRMC1, a multifunctional receptor belonging to membrane-associated progesterone receptor proteins (MAPR) family, as possible predictive marker for increased hormone-dependent breast cancer (BC) risk, a systematic research program has been performed, starting with different BC cells, continued with animal studies and finally with clinical studies with BC patients. Summary: In vitro studies showed dose- and time-dependent BC cell proliferations with all available synthetic progestogens (not with progesterone), but mostly significant only in the presence of PGRMC1. Different animal (xenograft) studies confirmed that synthetic progestogens, but not progesterone and dydrogesterone, increased the estradiol-induced tumor proliferation, although with dydrogesterone, a small time-dependent increase could be seen. Clinical studies with hormone replacement therapy (HRT) to confirm these results are still running. In patients with BC expression of PGRMC1 in BC tissue was correlated to tumor characteristics like diameter, grade, and metastatic status. BC patients with PGRMC1 in the tumors had poorer disease-free and overall survival. After developing of an assay, blood levels could be correlated to the expression in BC tissue showing PGRMC1 superior to tumor markers such as CEA, CA125, CA153, and TPS. Key Messages: This review is summarizing two different functions of PGRMC1: (1) to predict the prognosis of BC patients, already well demonstrated in BC patients and (2) being a possible predictive marker for BC risk during HRT as suggested from in vitro and animal research. [ABSTRACT FROM AUTHOR]

Sex differences among neurones in the ventrolateral region of the ventromedial hypothalamic nucleus (VMHvl) allow for the display of a diversity of sex-typical behaviours and physiological responses, ranging from mating behaviour to metabolism. Here, we review recent studies that interrogate the relationship between sex-typical responses and changes in cellular phenotypes. We discuss technologies that increase the resolution of molecular profiling or targeting of cell populations, including single-cell transcriptional profiling and conditional viral genetic approaches to manipulate neurone survival or activity. Overall, emerging studies indicate that sex-typical functions of the VMH may be mediated by phenotypically distinct and sexually differentiated neurone populations within the VMHvl. Future studies in this and other brain regions could exploit cell-type-specific tools to reveal the cell populations and molecular mediators that modulate sex-typical responses. Furthermore, cell-type-specific analyses of the effects of sexually differentiating factors, including sex hormones, can test the hypothesis that distinct cell types within a single brain region vary with respect to sexual differentiation.

Menopause is a natural stage of hormonal aging in women, accompanied by a series of symptoms that reduce the quality of life of a fully active person. As no therapy is entirely satisfactory, the race for a better option is in full swing. Our study objective is to investigate the most recent menopause studies on pharmacological resources, emerging therapies, and the particularities of hormonal replacement therapy (HRT). For this purpose, a comprehensive search was conducted in two main databases (PubMed and Web of Science) guided by the specific keywords "menopause" and "therapy" or "estrogen" or "progesterone" or "hormone replacement" during the last ten years period. Studies were eligible if they met certain criteria: randomized controlled trials (RCT) in adult women with menopause and hormonal or non-hormonal therapies. We selected 62 RCTs, which are focused on four main topics: (a) epidemiology of menopause-related symptoms, (b) hormonal replacement therapy (HRT) selective estrogen receptor modulators, (c) emerging therapies, and (d) menopause. HRT has proven a real health benefit for menopausal women; besides, complementary interventions must be considered. Further studies are needed on menopause and menopause-related therapies. The continuous updating of clinical experience will strengthen the therapeutic benefit and the decision to treat patients safely. This goal will fully access all therapeutic resources to address an unresolved health issue of active adult women. [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]

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Menopausal hormone therapy (MHT) is used to treat menopausal complaints including the genitourinary syndrome of menopause, to prevent osteoporosis, and to treat bleeding problems. Since these can be the indications also in young women, especially with POI (premature ovarian insufficiency) or with surgical menopause (bilateral oophorectomy), also the old term “Hormone Replacement Therapy (HRT)” is still used. The effective component is the estrogen component without relevant difference in the efficacy of the various MHT-preparations. Additional preventive benefits are reduction of cardiovascular disease (including prevention of diabetes mellitus and metabolic syndrome), reduction of colon cancer, and perhaps also Alzheimer's disease, if started within a “window of opportunity”, i.e. in perimenopause or within 6–10 years after menopause.Primary indication for progestogen addition is to avoid the development of estrogen-dependent endometrial cancer, i.e. addition not recommended in hysterectomized women. Two main schedules, sequential- or continuous-combined estrogen/progestogen regimens, are used for treatment of bleeding problems. For this and for optimizing menstrual regulation detailed recommendations are given including proposed dosages for the available different progestogens if added to oral or transdermal estradiol in different estrogen dosages.The WHI-study demonstrated the main risks using MHT within a “worst-case scenario”, i.e. start of MHT in old women with high risk for breast cancer and cardiovascular diseases, whereby only “conjugated equine estrogens” and “medroxprogesterone acetate” have been tested. One main result was that the progestogen component is decisive for the risk of breast cancer, which according to own experimental research and observational studies may be reduced using the physiological progesterone or its isomer dydrogesterone. In addition we propose to push forward research for screening patients with increased breast cancer risk like we have done in the past decade demonstrating that certain membrane-bound receptors in breast cancer tissue or blood can increase this risk. To reduce the risk of venous thromboembolism and stroke, transdermal estradiol (gels, patches,) should be used, in free combination with progesterone or dydrogesterone as “golden standard” in patients with increased risk. To increase the compliance in our patients without special risks we mostly use the available fix-combinations of estradiol/dydrogesterone getting strong efficacy, good menstrual regulation or amenorrhea, respectively, but also other combinations may be indicated to take advantage of for example androgenic or antiandrogenic progestogens.

High-grade serous ovarian cancer (HGSOC) represents the most lethal subtype of ovarian cancer, largely due to being commonly diagnosed at advanced stages. The early molecular mechanisms underlying ovarian carcinogenesis remain poorly defined, posing challenges to the development of prevention and early detection strategies. Here we dissect the molecular mechanisms of sex steroid hormone signaling throughout the decades-long evolution of HGSOC precursor lesions, which predominantly originate from secretory epithelial cells of fallopian tubes (FT). We also discuss the prognostic significance of sex steroid receptor isoforms and steroid metabolizing enzymes in HGSOCs. Finally, we provide a comprehensive gene expression atlases of sex steroid receptors, steroidogenic, and steroid-metabolizing enzymes across different cell populations in pre- and postmenopausal FTs, and HGSOCs, using published single-cell RNA sequencing datasets. These atlases reveal that secretory epithelial cells and stromal populations in FTs express sex steroid receptors and enzymes responsible for the formation and inactivation of genotoxic estrogen metabolites. In HGSOC, epithelial cells express various HSD17B isoforms and steroid conjugating enzymes, suggesting an enhanced ability to finely regulate the levels of bioactive sex steroids. [Display omitted] • Sex steroids play an active role in the evolution of precursor lesions of high-grade serous ovarian cancer (HGSOC). • Progesterone receptor (isoforms A, B, and C) is strongly linked to platinum sensitivity and better survival in patients with HGSOC. • Sex steroid receptors and enzymes for catechol estrogen metabolism are present in secretory epithelial and stromal cells of FTs. • The cancerous epithelial population in HGSOCs expresses multiple HSD17B isoforms and steroid-conjugating enzymes, indicating its ability to regulate bioactive sex steroids. [ABSTRACT FROM AUTHOR]

Menopausal hormone therapy (MHT) has been widely used for the clinical treatment of symptoms associated with menopause in women. However, the exact nature of the relationship between MHT and the increased risk of breast cancer has not been fully elucidated. The results of the Women’s Health Initiative’s randomized controlled clinical studies showed that estrogen monotherapy was associated with a lower incidence of breast cancer as compared to estrogen-progesterone combined therapy, with an elevated risk of breast cancer. The evidence currently available from randomized trials and observational studies is based on data from different populations, drug formulations, and routes of administration. Even though the risks of MHT and breast cancer have received a great deal of attention, information regarding the unpredictable toxicological risks of estrogen and progestogen metabolism needs to be further analyzed. Furthermore, the diversity and complexity of the metabolic pathways of estrogen and different progestogens as well as the association of the different estrogen and progestogen metabolites with the increased risk of breast cancer need to be adequately studied. Therefore, this review aimed to describe the biological effects of estrogen, progesterone, and their metabolites on the proliferation of breast cancer cells, based on relevant basic research and clinical trials, to improve our understanding of the biological functions of estrogen and progestogen as well as the safety of MHT.

Vaginal progesterone (VP) has been recommended to prevent preterm birth (PTB) in women at high-risk. However, there is controversy as to whether VP is efficacious in some subsets of high-risk women. In this review, we examined the current best evidence on the efficacy of VP to prevent PTB in several subsets of high-risk women and provided recommendations for its clinical use. Compelling evidence indicates that VP reduces the risk of PTB and improves perinatal outcomes in singleton gestations with a short cervix (≤25 mm), both with and without a history of spontaneous PTB. VP appears promising to reduce the risk of PTB in twin gestations with a short cervix (≤25 mm) and in singleton gestations conceived by assisted reproductive technologies, but further research is needed. There is no convincing evidence that supports prescribing VP to prevent PTB in singleton gestations based solely on the history of spontaneous preterm birth. Persuasive evidence shows that VP does not prevent PTB nor does it improve perinatal outcomes in unselected twin gestations and in singleton gestations with a history of spontaneous PTB and a cervical length >25 mm. There is no evidence supporting the use of VP to prevent PTB in triplet or higher-order multifetal gestations, singleton gestations with a positive fetal fibronectin test and clinical risk factors for PTB, and gestations with congenital uterine anomalies or uterine leiomyoma. In conclusion, current evidence indicates that VP should only be recommended in singleton gestations with a short cervix, regardless of the history of spontaneous PTB. [ABSTRACT FROM AUTHOR]

Despite increasing recognition that sex is a critical variable in appetite research, many studies fail to include participants of both sexes, fail to consider reproductive physiology in participant selection, or include both sexes but fail to test for sex differences in outcomes. To help remedy this situation, this article seeks to engender enthusiasm for including sex as a variable in appetite research. We first illustrate some sex differences in healthy and disordered eating, including both male-female differences and differences across the menstrual cycle. We next provide methodological guidance for studies involving male and female participants around puberty, during reproductive adulthood, and during reproductive senescence. Studies in children ≥5 y of age should consider adrenarche and gonadarche. Appetite studies in girls and women following menarche and similarly aged males should consider the influences of sex-specific aspects the hypothalamic-pituitary-gonadal (HPG) axis function. The cyclicity of HPG function (i.e., the menstrual cycle) in girls and women presents the challenge of identifying of menstrual-cycle subphases, which are highly variable within and between individuals. Reproductive senescence refers to changes in HPG axis function that occur in both men and women beginning in mid-life. Current best practices involve consideration of hormone-assay methodology, experimental design, and statistical analyses. On the horizon are options based on wearable-sensors and nanotechnology. Well informed consideration of sex as a variable will accelerate progress in appetite research by increasing rigor, replicability, and relevance., Competing Interests: Declaration of competing interest None of the authors has conflicts of interest to declare., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Objective of this review is a systematic analysis of the data available in the current literature on the efficacy and safety of progestogens for the prevention of atypical endometrial hyperplasia (EH) in patients of reproductive age. EH is an excessive proliferation that results in increased volume and changes in endometrial tissue architectonics with an increase in the endometrial glands to stroma ratio of more than 1:1. This review will consider the use of progestogens for the prevention of (EH) based on evidence-based scientific evidence over the past 5 years. The expansion of the range of effective treatment options allows the adaptation of treatment to the needs of patients and offers a personalized approach to their management. Progestogens are an effective and safe method for the prevention of atypical hyperplasia, with a wide range of therapeutic benefits associated with reliable favorable fertility prognosis, especially in young women.

Objective: Atypical polypoid adenomyoma (APA) is a rare uterine premalignant lesion mainly occurring in premenopausal and nulliparous women. Although hysteroscopic resection (HR) has showed promising results, the conservative management of APA in young women is not standardized, and few data are available in the literature. We aimed to assess oncologic outcomes of the conservative treatment of APA. Methods: A multicenter observational retrospective cohort study was performed including all patients with APA who underwent conservative treatment from January 2006 to June 2020. Rates of each oncologic outcome (i.e. initial complete response, persistence, progression to cancer, recurrence, long‐term treatment success, and treatment failure) were calculated for all conservative treatment together and separately. Results: Twenty‐five patients were included. Conservative treatments consisted of HR alone (n = 14) and HR + progestin (n = 11). Overall, 24 (96%) patients showed initial complete response, of which 21 (84%) showed long‐term treatment success; four (16%) patients had progression to cancer, of which two (8%) first recurred as APA. Long‐term treatment success was achieved in 13 of 14 (92.9%) patients with HR alone and 8 of 11 (72.3%) with HR + progestin. Conclusion: Conservative treatment appears to be a safe option in women with APA. The four‐steps HR might be considered as the first‐line conservative approach, while the addition of progestin does not seem to improve oncologic outcomes. However, the risk of progression to cancer highlights the need for a close and long‐term follow up with ultrasonography and hysteroscopic biopsies, and for hysterectomy in patients not desiring pregnancy. Conservative treatment appears safe in women with APA; four‐step HR might be a first‐line conservative approach, while adding progestins seems to not improve oncologic outcomes. [ABSTRACT FROM AUTHOR]

Brown bears are obese when they enter the den, and after 6 mo of hibernation and physical inactivity, bears show none of the adverse consequences of a sedentary lifestyle in humans, such as cardiovascular disease, type 2 diabetes, and kidney failure. The metabolic mechanisms that drive hibernation physiology in bears are poorly defined, but systemic endocrine regulators are likely involved. To investigate the potential role of steroid hormones, we quantified the total levels of 12 steroid hormones, the precursor cholesterol, sex hormone–binding globulin (SHBG), and corticosterone-binding globulin (CBG) in paired serum samples from subadult free-ranging Scandinavian brown bears during the active and hibernation states. During hibernation, androstenedione and testosterone were significantly decreased in subadult female bears (n = 13), whereas they increased in all males but one (n = 6) and therefore did not reach a significant difference. Despite this difference, SHBG increased more than 20-fold during hibernation for all bears. Compared with SHBG concentrations in humans, bear levels were very low in the active state, but during hibernation, levels equaled high levels in humans. The increased SHBG levels likely maintain a state of relative quiescence of the reproductive hormones in hibernating bears. Interestingly, the combination of SHBG and testosterone levels results in similar free bioavailable testosterone levels of 70–80 pM in both subadult and adult sexually active male bears, suggesting a role for SHBG in controlling androgen action during hibernation in males. Dehydroepiandrosterone sulfate, dihydrotestosterone, and estradiol levels were below the detection limit in all but one animal. The metabolically active glucocorticoids were significantly higher in both sexes during hibernation, whereas the inactive metabolite cortisone was reduced and CBG was low approaching the detection limit. A potential caveat is that the glucocorticoid levels might be affected by the ketamine applied in the anesthetic mixture for hibernating bears. However, increased hibernating cortisol levels have consistently been reported in both black bears and brown bears. Thus, we suggest that high glucocorticoid activity may support the hibernation state, likely serving to promote lipolysis and gluconeogenesis while limiting tissue glucose uptake to maintain a continuous glucose supply to the brain. [ABSTRACT FROM AUTHOR]

Background and purpose: A dose‐dependent association between the use of cyproterone acetate (CPA) and intracranial meningioma has been identified but data for other potent progestogens are scarce. The association was assessed between intracranial meningioma surgery and exposure to three potent progestogens: CPA (≥25 mg/day), nomegestrol acetate (NOMAC) (3.75–5 mg/day) and chlormadinone acetate (CMA) (2–10 mg/day). Methods: In this nationwide population‐based case–control study, cases underwent surgery for intracranial meningioma in France from 2009 to 2018. They were matched to five control subjects for sex, year of birth and area of residence. Progestogen exposure was defined as progestogen use within the year before surgery for cases or the same date for their controls. Results: In total, 25,216 cases were included (75% women, median age 58 years). Progestogen exposure was noted for 9.9% of cases (2497/25,216) and 1.9% (2382/126,080) of controls, with an odds ratio (OR) of 6.7 (95% confidence interval [CI] 6.3–7.1). The OR was 1.2 (1.0–1.4) for short‐term use (<1 year) and 9.5 (8.8–10.2) for prolonged use. A strong association was identified for prolonged use of CPA (OR = 22.7, 95% CI 19.5–26.4), NOMAC (OR = 6.5, 95% CI 5.8–7.2) and CMA (OR = 4.7, 95% CI 4.5–5.3). Progestogen exposure increased the risk of meningioma for all histological grades and anatomical sites, particularly for the anterior and middle skull base: OR = 35.7 (95% CI 26.5–48.2) and 23.9 (95% CI 17.8–32.2) for CPA. The estimated number of attributable cases was 2124 (95% CI 2028–2220) (212/year). Conclusion: A strong association between prolonged exposure to potent progestogens and surgery for meningioma was observed. The risk increased from CMA to NOMAC to CPA. Individuals should be informed of this risk. This study highlights a strong association between prolonged use of nomegestrol and chlormadinone acetate (two potent progestogens) and intracranial meningioma, although weaker than that of cyproterone acetate. The estimated number of cases was higher than 2000 in France over 10 years. [ABSTRACT FROM AUTHOR]

Background: The literature is full of papers reporting side effects of progestogens in cats; however, they are, in fact, safe drugs, as discussed in this article. Gonadotropin-releasing hormone (GnRH) agonists and melatonin are additionally a practical solution for controlling cyclicity in queens, but they also have some contraindications and need to be used carefully. Clinical relevance: Mastering the use of reproductive drugs allows feline practitioners to handle many more clinical situations than can be solved using surgery. It is not necessary to be a specialist in reproduction to be able to halt cyclicity in a valuable breeding queen using hormones. Equipment and technical skills: A sound knowledge of appropriate dosages and criteria for patient selection for all reproductive drugs currently used in feline reproduction is the best guarantee of owner satisfaction and of ensuring the queen's health. Availability of a serum progesterone assay, either in-house or via an external laboratory, is also important, in order to confirm a queen is at an appropriate stage of the reproductive cycle for treatment. Audience: This article is aimed principally (but not exclusively) at veterinarians working with cat breeders and whose clientele is increasingly interested in alternative methods of controlling reproduction in pet queens. Surgery is no longer the only choice, and practitioners who manage to keep abreast of new developments will be able to address clients' needs in a modern, professional way. Evidence base: This review draws on a vast body of scientific evidence-based literature. Previously, personal (and sometimes misinformed) opinions, such as the proposed dangerous side effects of progestogens, have been perpetuated in the scientific literature. The papers cited in this review have therefore been carefully scrutinised to distinguish reliable information based on controlled studies from non-evidence-based information. [ABSTRACT FROM AUTHOR]

Endometriosis remains an unresolved problem in gynecology. The urgency of the fight against this disease is due to its high prevalence among women of reproductive age. Endometriosis, especially its infiltration forms, affects all aspects of the patients life, its clinical manifestations pelvic pain, dyspareunia, dysmenorrhea, dyschezia, lead to social disadaptation, problems in personal life, depression and anxiety. The socio-economic burden of the disease motivates researchers to further study the pathogenesis of endometriosis and search for pathogenetically justified pharmacological solutions.

Mass spectrometric-based steroidomics is a valuable analytical approach that gives a comprehensive understanding of the interlinked steroid biosynthetic pathways. Here, we describe a rapid and versatile liquid chromatography-tandem mass spectrometry (LC-MS/MS) method designed to accurately quantify endogenous steroids in human serum. Sample preparation involved liquid-liquid extraction with methyl tert -butyl ether (MTBE) from 180 µL serum. The targeted steroids for quantification included androgens: dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T), dihydrotestosterone (DHT), 11-oxyandrogens: 11β-hydroxy-androstenedione (11OHA4), 11-keto-androstenedione (11KA4), 11β-hydroxy-testosterone (11OHT), 11-keto-testosterone (11KT), progestogens: 17α-hydroxy-progesterone (17OHP4), progesterone (P4), 11β-hydroxy-progesterone (11OHP4), 11-keto-progesterone (11KP4), mineralocorticoids: aldosterone, corticosterone, and glucocorticoids: 11-deoxycortisol, cortisol, and cortisone. The lower limits of quantification (LLOQ) were 0.05 ng/mL for A4, T, 11KA4, P4, and cortisone, 0.1 ng/mL for DHT, 11OHA4, 11OHT, 11KT, 17OHP4, 11OHP4, 11KP4, corticosterone, aldosterone, 11-deoxycortisol, and cortisol, and 0.5 ng/mL for DHEA. Accuracy, precision, reproducibility, and recovery fell within acceptable limits for bioanalytical method validation. Using serum samples from 29 premenopausal women in different menstrual phases, we demonstrated the clinical utility of our method, which showed sufficient sensitivity to reliably quantify all targeted steroids at levels typically found in circulation, except for 11OHP4 and 11KP4. • This multi-steroid profiling assay quantifies 17 steroids in 15 min. • This assay simultaneously quantifies endogenous steroids from several biosynthetic pathways. • We present analytical data validated for serum multi-steroid profiling. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • A single, reusable and biodegradable G-MNPs-agarose film was prepared for progestogens extraction. • The film presented excellent mechanical properties and high extraction efficiency. • The film was reusable for 70 times without losing its extraction capacity. [ABSTRACT FROM AUTHOR]