Search

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.

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.

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.

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

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.

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.

Non-atypical endometrial hyperplasia (EH) is prone to recurrence and has an unspecified residual monitoring and treatment algorithm. The main factors that influence the possibility of recurrence and progression are not known yet.The objective: examination of the frequency of hyperproliferative endometrial pathology (HPE) in premenopausal women, organization of treatment and prophylactic measures and their influence on the recurrence or progression of HPE.Design of the study: a retrospective observational study. Results of the study: The results of monitoring and treatment were analysed in 380 premenopausal women according to STRAW+10 criteria. The structure was dominated by non-atypycal endomrtrial hyperplasia (EH)- in 356 (93.7%) cases, atypycal hyperplasia (AH) - in 16 (4.2%), endometrial cancer (EC) - in 8 (2.6%). 60 women underwent hysterectomy (24 - AH and EC, 36 - concomitant pathology). Results from 320 women with EH excluding hysterectomy, have been monitored over 3 years. Hormonal treatment with gestagens was given to 138 of 320 women (43.1%), 78 (24.3%) received oral progestins without an interruption for 3 months, 34 (10.6%) for 6 months and 26 (8.1%) received LNG-IUDs 52 mg, in 182 (56.8%) no treatment was provided. The effectiveness of EH therapy in women with LNG-IUDs was achieved in 92.3% of cases, with gestagen treatment at 6 months in 70.6%, and at 3 months in 39.7%. With no therapy, regression of the disease was 28.8%. The incidence of EH at the 3rd year of follow-up in women without treatment was 2.4 times higher than at the 6-month course of oral gestagen therapy (71.4 vs 29.4%) and was not significantly different from the 3-month course (71.4 vs 60.3%).There is a lack of clarity in the treatment and monitoring system for women with EH in the study centres; short timing of gestagen prescriptions are insufficiently effective and contribute to a high rate of recurrence; the LNG IUD showed the best efficacy results (93.7%) and absence of recurrence over the course of the study.

Background. Most common clinical manifestations of endometriosis (N80) include pelvic pain and infertility, while adenomyosis is associated with abnormal uterine bleeding. At present, approach to the treatment of endometriosis has been revised towards shifting surgery to the second-line therapy; medications are considered as the first-line therapy: gonadotropin releasing hormone agonists, progestogens, aromatase inhibitors. Aim. Comparison of clinical and anamnestic characteristics and therapeutic procedures in women who were treated on an outpatient basis and those who were hospitalized and underwent surgical intervention. Materials and methods. Clinical-anamnestic and morphological characteristics were studied in two groups of women: 1st group (n=27) received drug therapy, 2nd group (n=28) underwent surgical intervention. Results and discussion. In the 1st group, 25.9% of patients received microdosed combined oral contraceptives which contain dienogest as a progestogen component, 44.4% of patients received monotherapy with dienogest, and 22.2% of patients received dydrogesterone in a prolonged mode. In the 2nd group, 39 foci of endometriosis, isolated and in a combination of various loci, were revealed during surgery, of which 30.8% were ovarian cysts, 10.2% were foci on the sacro-uterine ligaments, 23.1% were on the pelvis peritoneum. Surgical approach was determined by the urgency of intervention, an expect localization of endometriosis foci, a comorbidity of endometriosis with another pathology of the internal genitalia, 82.1% of surgery were performed by laparoscopic approach. Conclusions. The choice of treatment method depends on the severity of symptoms, the severity of endometriosis, the woman age and her reproductive intentions. When choosing a surgical treatment, one should be guided not only by the need for the most radical removal of endometriosis foci, but also should consider a surgical approach to minimize discomfort and provide a good quality of life after surgery. A three-stage model for the management of patients with endometriosis is proposed, which includes an assessment of treatment effectiveness and the need to develop a rehabilitation program.

Habitual miscarriage is a fairly common complication of early pregnancy. In the opinion of most authors, the term habitual miscarriage is used to describe a loss of two or more pregnancies during the first 22 weeks of pregnancy. Issues of terminology and management continue to be relevant and debatable in medical professional communities and need further discussion. In addition to the medical sides of the issue, habitual miscarriage has a significant psychological impact on women and their partners. Regardless of the gestational age, the loss of pregnancy for most couples is similar in importance to the loss of a newborn and is associated with the loss of hope and plans that future parents connected with a baby who has not yet been born. After repeated losses, bereavement and emotional upheaval are further exacerbated irrespective of the term of abortion. Repeated pregnancy loss is a significant negative event in the life of a couple both from a medical and psychological point of view, that’s why the provision of adequate medical care is one of the objectives of a specialist managing pregnancy. This also involves the choice of effective disease management. Previously it was shown that luteal phase deficiency might be the cause of this phenomenon, and that hormonal deficiency had to be replenished. Many modern publications confirm that progesterone and its derivatives have an important immunomodulatory role in the habitual miscarriage. The article describes the role of progesterone in maintaining pregnancy and the results of studies devoted to the role of dydrogesterone. It also presents data of international studies on the treatment of women with habitual miscarriage.

The article tells about the use of a combined contraceptive preparation containing the novel progestogen - dienogest - in conservative antirecurrent treatment of endometriosis. According to current concepts, endometriosis is a chronical dishormonal, immunodependent, multifactorial, genetically determined disease which manifests itself in the growth and presence of endometrioid heterotopias in the uterus. While accurate diagnosis and ablation of heterotopias require surgery, for subsequent treatment, doctor's toolkit offers a multitude of medicines the effects of which are on the whole described by the following: fight against manifestations of endometriosis, inhibition of the progression of the process, reduction of the disease recurrence, and improving the quality of life of patients. Pharmacotherapy of endometriosis should be effective and safe. Dienogest demonstrated properties comparable to those of gonadotropin-releasing hormone agonists, especially for early clinical manifestations of endometriosis. The combined contraceptive containing ethinylestradiol and dienogest is best suited for long-term (several months) treatment of endometriosis under a cyclic or continuous regimen.

Endometriosis, with more than centenary history, remains a challenge in our day. One of the more common options is adenomyosis, the share of which amounts to 80%. The aim of the study was to evaluate the clinical effectiveness and tolerance to resolve with chronic pelvic pain syndrome of adenomyosis the use of progestogen-new generation dienogest in a dose of 2 mg for 6 months. The study included 44 (n=44) women of reproductive age with a diagnosis of adenomyosis with chronic pelvic pain syndrome of various degrees of severity, whose average age was on average 36 yo 2 years who received therapy with dienogest in a daily dose of 2 mg for 6 months. The results showed high therapeuticefficiency dienogest in the treatment of pelvic pain caused by adenomyosis.

Postmenopausal women using continuous combined estrogen/progestin therapy are likely to have irregular bleedings or spotting. Up to now, their causes remain unclear. Most investigators believe that a potential mechanism of abnormal bleedings during menopausal hormonal therapy could be a change in the ratio of pro- and anti-angiogenic factors, namely, of vascular endothelial growth factor to thrombospondin-1; alterations in metalloproteinases and their tissue inhibitors; changes in a tissue factor that is a mediator of endometrial hemostasis; as well as an increased number of endometrial leukocytes with predominance of uterine natural killer cells. As long as no link between bleeding discharge during continuous combined hormonal treatment and any of these actors has been established, each and every of them is the subject of in vivo and in vitro investigations. At present, there are no herapeutic methods to correct this complication of hormonal treatment. Patient monitoring to exclude neoplastic abnormalities in endometrium are of paramount importance.

This review of literature is devoted to the study of highly selective progestogen of the last generation - nomegestrol acetate. Showing its high antigonadotropic effect, as well as selective effect on the progesterone receptors, and low binding to other receptors, which results in a low incidence of side effects. No less significant are the high contraceptive efficacy, acceptability and lack of influence on the parameters of hemostasis, blood lipid profile, mammary glands.

Hormone therapy is widely used in obstetric practice for the treatment of miscarriage, but, despite the known facts about the decisive influence of hormones on the sexual differentiation of the brain, long-term effects of intrauterine exposure to steroid drugs (drugs) on the formation of sexual behavior insufficiently studied. Therefore, the purpose of the study was to assess the performance of psychosexual development of children whose mothers received hormonal drugs during pregnancy. The cross-sectional study included 148 children whose mothers took estrogens and/or progestogens, and/or glucocorticoids, or did not take steroids (control group). The evaluation of indicators of mental development of children using the methods of «Age and gender identification», «Figure-posture-clothing», «Picture yourself», «Drawing the human behind the front» has been held.Results. Most of the children's sexual development was in line with the norm, gender and age identification formed by age and without features, elements of sexual dysontogenesis observed in isolated cases. Deviations were more common in girls whose mothers took estrogens and progestogens, and boys whose mothers received corticosteroids, but the proportion of these children were not significantly different from the proportion of children in the group of women who did not receive hormone therapy.Conclusion. The data obtained refute assumptions about the relationship of hormonal drugs during pregnancy with the development of disorders of puberty and sexual behavior anomalies in the offspring.

Insulin resistance in patients with obesity leads to indirect menstrual cycle disruption through hyperinsulinemia and hyperleptinemy. In order to correct menstrual disorders, the metabolic characteristics of the optimal progestin should be considered, so that the already existing disorders of fat and carbohydrate metabolism may not be aggravated even more.

The most common treatment for menopausal syndrome is menopausal hormone therapy (MHT), however, the safety of MHT, due to the risk of developing and recurrent breast cancer (BC), is still a matter of debate. The review presents the results of randomized cohort studies of this issue. It has been shown that MHT increases the risk of developing of breast cancer and disease recurrence after treatment. Risk of breast cancer developing in women getting MHT, depends on body mass index (BMI), duration of hormone use and dose of drugs, and is greater in thin women comparing with women with increased BMI, and also greater in estrogen-progestin combined MHT users comparing with estrogen-only users. It was found that in women using MHT hormone-dependent forms of cancer developed more often, but by the time of diagnosis, disease was found in more advanced stage and metastases in lymph nodes were found more often comparing with patients who did not use MHT. Risk of breast cancer recurrence is less with the use of low doses of vaginal estrogen. An alternative option for the relief of menopausal disorders in breast cancer patients during and after treatment is using of pineal gland hormone melatonin, since, along with its anti-aging properties, it is able to suppress cancer at the stages of initiation, progression and metastasis and has the ability to reduce the toxic effects of anticancer drugs while increasing their effectiveness.