Use Of Progestins Research Articles

Frequent Use of Premenopausal Progestin in Prior Pre-Eclamptic Women.

Women with a history of pre-eclamptic pregnancy are predisposed to later occlusive vascular diseases. We compared the use of cyclic progestins or levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of menstrual cycle abnormalities between premenopausal women with and without a prior pre-eclamptic pregnancy. Register-based cohort study during 1994-2019 of oral progestin or levonorgestrel-releasing intrauterine device (LNG-IUD) in Finnish women with (n=31 688) and without (n=91 726) prior pre-eclampsia in 1969-1993. Cyclic progestin or LNG-IUD use and its association with future use of menopausal hormone therapy (MHT). Prior pre-eclamptic women had used cyclic progestins more often (23.5% vs. 9.1%; p<0.001) and initiated the use at younger ages (41.8 years [SD=6.3] vs. 45.9 years [3.1]; p<0.001) than control women. Also, LNG-IUD was inserted more frequently (p<0.001) in prior pre-eclamptic women (9.3%) than in controls (4.7%). Cyclic progestin or LNG-IUD use was accompanied by significant 37-90% elevations in future MHT use. Increased use of cyclic progestins and LNG-IUD in premenopausal women with a history of pre-eclamptic pregnancy can be seen as indirect evidence of earlier onset of ovulatory dysfunction. This may contribute to the elevated risk of endometrial cancer in these women. Our findings may indicate one additional late sequela of pre-eclamptic pregnancy.

12330 Progestogen Experience And Perception Among Transfeminine Adults - A National Survey

Abstract Disclosure: J.J. Chang: None. N. Khai Tran: None. A. Flentje: None. M.E. Lubensky: None. J. Obedin-Maliver: Consulting Fee; Self; Ibis Reproductive Health, Hims, Incorporated, Folx, Incorporated, Upstream, Incorporated. M.R. Lunn: Consulting Fee; Self; Hims, Incorporated, Otsuka Pharmaceutical Development and Commercialization, Inc., American Dental Association. D. Ariel: None. Background: Current guidelines recommend estradiol with consideration of anti-androgens for gender-affirming hormone therapy (GAHT) in transfeminine adults. Many individuals also seek progestogens as part of feminizing GAHT, particularly to enhance breast development. Though progestogen use seems common, few studies describe its use, reported benefits, and side effects. SpecificAims: 1) To describe progestogen use in feminizing GAHT among transfeminine individuals in the U.S. 2) To evaluate reasons for progestogen initiation and perceived physical and emotional impact; 3) To investigate side effects and adverse events. Materials and Methods: In this cross-sectional study, participants were recruited from The PRIDE Study, a U.S.-based longitudinal cohort study of LGBTQIA+-identifying adults. Included participants were assigned male sex at birth and had a feminine/transfeminine or non-binary gender identity. Those assigned female sex at birth (AFAB) or born with 1 or more ovaries were excluded. Descriptive statistics were used to describe socio-demographic characteristics, progestogen use patterns, initiation reasons, perceived physical and mental impacts, side effects, adverse events, and care satisfaction. Results: 543 participants were eligible and completed the study. Mean age was 43.2 years (standard deviation: 14.9). Of 310 progestogen users, the most common progestogen forms were micronized progesterone (58.4% oral; 10.6% rectal) and medroxyprogesterone acetate (7.7% oral). Median progestogen use duration was 2 years (interquartile range: 1-4). Breast development (85.2%) and mimicking the hormone pattern of those AFAB (58.1%) were the two most reported reasons for progestogen initiation. Most progestogen users reported improved breast development (79.7%); none reported worsening. Sex drive, sleep, and concentration did not change with progestogen use in 46.5%, 51.3%, and 73.9% of participants, respectively. Adverse events included lower extremity deep vein thrombosis (n = 6) and pulmonary embolism (n = 4). The most common side effects were breast pain (28.7%), mood fluctuation (21.9%), fatigue (19.7%), and weight gain (19.0%). Most users expressed satisfaction with progestogens (71.9%) and would recommend to others (73.5%). Among 68 former progestogen users, 20.6% reported stopping progestogens due to negative side effects, and 32.4% stopped due to lack of perceived efficacy. Conclusions: In the largest study describing progestogens in GAHT to date, over half of transfeminine adults used progestogens, particularly for breast development. Most reported improvement with breast development and overall satisfaction. However, perceived impacts on other effects were variable. Future prospective studies are needed to investigate the effects of progestogens versus other components of feminizing GAHT. Presentation: 6/1/2024

12330 Progestogen Experience And Perception Among Transfeminine Adults - A National Survey

Abstract Disclosure: J.J. Chang: None. N. Khai Tran: None. A. Flentje: None. M.E. Lubensky: None. J. Obedin-Maliver: Consulting Fee; Self; Ibis Reproductive Health, Hims, Incorporated, Folx, Incorporated, Upstream, Incorporated. M.R. Lunn: Consulting Fee; Self; Hims, Incorporated, Otsuka Pharmaceutical Development and Commercialization, Inc., American Dental Association. D. Ariel: None. Background: Current guidelines recommend estradiol with consideration of anti-androgens for gender-affirming hormone therapy (GAHT) in transfeminine adults. Many individuals also seek progestogens as part of feminizing GAHT, particularly to enhance breast development. Though progestogen use seems common, few studies describe its use, reported benefits, and side effects. SpecificAims: 1) To describe progestogen use in feminizing GAHT among transfeminine individuals in the U.S. 2) To evaluate reasons for progestogen initiation and perceived physical and emotional impact; 3) To investigate side effects and adverse events. Materials and Methods: In this cross-sectional study, participants were recruited from The PRIDE Study, a U.S.-based longitudinal cohort study of LGBTQIA+-identifying adults. Included participants were assigned male sex at birth and had a feminine/transfeminine or non-binary gender identity. Those assigned female sex at birth (AFAB) or born with 1 or more ovaries were excluded. Descriptive statistics were used to describe socio-demographic characteristics, progestogen use patterns, initiation reasons, perceived physical and mental impacts, side effects, adverse events, and care satisfaction. Results: 543 participants were eligible and completed the study. Mean age was 43.2 years (standard deviation: 14.9). Of 310 progestogen users, the most common progestogen forms were micronized progesterone (58.4% oral; 10.6% rectal) and medroxyprogesterone acetate (7.7% oral). Median progestogen use duration was 2 years (interquartile range: 1-4). Breast development (85.2%) and mimicking the hormone pattern of those AFAB (58.1%) were the two most reported reasons for progestogen initiation. Most progestogen users reported improved breast development (79.7%); none reported worsening. Sex drive, sleep, and concentration did not change with progestogen use in 46.5%, 51.3%, and 73.9% of participants, respectively. Adverse events included lower extremity deep vein thrombosis (n = 6) and pulmonary embolism (n = 4). The most common side effects were breast pain (28.7%), mood fluctuation (21.9%), fatigue (19.7%), and weight gain (19.0%). Most users expressed satisfaction with progestogens (71.9%) and would recommend to others (73.5%). Among 68 former progestogen users, 20.6% reported stopping progestogens due to negative side effects, and 32.4% stopped due to lack of perceived efficacy. Conclusions: In the largest study describing progestogens in GAHT to date, over half of transfeminine adults used progestogens, particularly for breast development. Most reported improvement with breast development and overall satisfaction. However, perceived impacts on other effects were variable. Future prospective studies are needed to investigate the effects of progestogens versus other components of feminizing GAHT. Presentation: 6/1/2024

Progestin-primed ovarian stimulation

The use of progestins for the prevention of premature ovulation during ovarian stimulation is called progestin-primed ovarian stimulation (PPOS). Response to ovarian stimulation with PPOS and gonadotropin-releasing hormone (GnRH) analogs seem to be similar with the clinically insignificant differences being explained by endocrine characteristics as expected. PPOS has the advantage of oral administration and lower medication cost than GnRH analogs, but the mandatory cancellation of an otherwise possible fresh embryo transfer can render PPOS less cost-effective if a fresh transfer would have been possible. Oocytes collected in PPOS cycles have similar developmental potential, including blastocyst euploidy rates. Frozen embryo transfer outcomes of PPOS and GnRH analog cycles seem similar both in terms of ongoing pregnancy/live birth rates and obstetric and perinatal outcomes. While some studies reported lower cumulative live birth rates with PPOS, they suffer from methodological issues, including arbitrary definitions of cumulative live birth rates. PPOS has been used in all patient types with consistent results and seems a patient-friendly and cost-effective choice when a fresh embryo transfer is not intended.

Comparison of the clinical efficacy of dienogest and drospirone/ethinyl estradiol in the treatment of ovarian endometriosis cysts

Background: Ovarian endometriosis cysts (OEC) are common chronic diseases occurring in women of reproductive age. Hormone therapy, including the use of oral contraceptives (COCs) and progestins, is widely employed in the treatment of endometriosis and OEC. Objective: This study aims to compare therapeutic effects of long-term daily use of dienogest (DNG, 2 mg) versus drospirenone (DRSP, 3 mg)/ethinyl estradiol (EE, 20 μg) daily on ovarian endometrial cysts, particularly focusing on cysts suppression. Methods: A retrospective analysis was conducted on 84 patients diagnosed with OEC, with 42 receiving DNG and 42 treated with DRSP/EE. After 6 months, assessments were made regarding pain symptoms, size of OEC, tumor markers, and adverse reactions. Results: After 6 months of treatment, both DNG and DRSP/EE effectively alleviated pain in patients with ovarian endometriotic cysts. DNG demonstrated more significant improvements than DRSP/EE in reducing tumor size, mainly in terms of higher drug efficacy and greater percentage of tumor shrinkage. However, DRSP/EE significantly reduced the expression of the tumor markers CA125 and CA199 in our study. Patients taking DNG had a higher likelihood of experiencing side effects than those on DRSP/EE, mainly vaginal bleeding and irregular menstrual periods. Conclusions: Both DNG and DRSP/EE are effective in treating ovarian endometrial cysts. DNG appears to be superior in terms of tumor reduction, while DRSP/EE more significantly decreases the expression of the tumor markers and has fewer side effects.

Levonorgestrel intrauterine system versus dienogest effect on quality of life of women with deep endometriosis: a randomized open-label clinical trial

ABSTRACT Women with deep infiltrating endometriosis (DIE) can benefit from the use of progestins. Our aim is to explore if levonorgestrel-releasing intrauterine system (LNG-IUS) non inferior to dienogest (DNG) in improving deep endometriosis women’s quality of life (QoL). This randomized open-label clinical trial included forty women with DIE assessed using clinical history and physical examination, transvaginal ultrasonography and magnetic resonance of the pelvis without any previous surgical treatment, with two treatments arms. The two groups underwent a 3-month washout of hormonal treatments, and then received either DNG or LNG-IUS for 6 months. QoL was assessed prior to and 6 months after the intervention, using the SF36 and the EHP30. DNG and LNG-IUS showed an increase on all domains of the SF36 (p < .001). There was no difference between treatments on the improvement observed (p > .05 for all domains). DNG and LNG-IUS, also, showed improvement on all domains of EHP30 (p < .001), except “relationship with children” and “feelings about pregnancy.” However, there was no statistical difference between treatments for all sections scores (p > .05). The treatment of deep endometriosis symptoms using either DNG or LNG-IUS in women with no prior surgical treatment is associated with improvement in QoL. Trial Registration Number: This trial is registered on “The Brazilian Registry of Clinical Trials (ReBECID: RBR-8fjx2jp),” that is part of Primary Registries in the WHO Registry Network, under the title: “Dienogest versus Levonorgestrel IUS on deep endometriosis patient´s QoL without surgery” on June 14, 2021; https://ensaiosclinicos.gov.br/rg/RBR-8fjx2jp.

P-615 Can the use of progestin in egg donation cycles influence morphokinetic parameters of embryos when compared with GnRH antagonist during ovarian stimulation? A case-control study

Abstract Study question Are there differences in clinical and morphokinetic parameters of embryos obtained from fresh egg donation cycles using GnRH antagonist versus PPOS on same donor? Summary answer Lower number of oocytes retrieved and faster early morphokinetics parameters were observed in PPOS protocol. What is known already Controlled ovarian hyperstimulation (COH) is a crucial step in assisted reproduction treatments and the ideal protocol should be chosen according to the patient’s profile, based on literature results, intending to achieve high effectiveness. The use of PPOS in ovarian stimulation protocols is getting attention because of its safety, efficacy and proved to be patient friendly and an economical alternative to avoid premature LH surge. In the last years, morphokinetics parameters started to be considered in embryo classification and selection, as they correlate to embryo implantation potential. Here, morphokinetics parameters were compared from two different COH in donated oocyte cycles. Study design, size, duration Case-control study including cycles from 10 oocyte donors and 20 recipient patients, whose embryos formed with fresh oocytes were cultured in a time-lapse system (Embryoscope® Plus), in a single private IVF center between Jun/2020 and Oct/2022. Each donor were submitted to two cycles: first stimulation with standard GnRH antagonist (ant) short protocol (group A) and in a posterior cycle: a second stimulation with progesterone (PPOS protocol with dydrogesterone, group B). Participants/materials, setting, methods All donors used menotropin for COH (doses adjusted according to patient’s profile). Group A started GnRh ant with follicle above 14 mm. On group B, dydrogesterone 10 mg was started on the first day of COH and maintained until the day of ovulation trigger, which was performed with GnRH agonist. Clinical and morphokinetics parameters were compared. Paired t-test, t-test or Mann-Whitney were used properly, values of p &amp;lt; 0.05 were considered significant. Main results and the role of chance A total of 70 blastocysts were analyzed, 39 from group A and 31 from group B. The following morphokinetics parameters were annotated: time of PN fading (tPNf), time to two cells (t2), three cells (t3), four cells (t4), five cells (t5), eight cells (t8), time to morula (tM), time to blastulation (tB) and KIDScoreTM. Statistically significant differences were observed for tPNf: group a) 24,01 ± 3,28h versus b) 22,59 ± 2,48h, p = 0,0484, t2: a) 26,30 ± 3,24h versus b) 24,76 ± 2,27h, p = 0,0211; t3: a) 37,04 ± 4,44h versus b) 35,53 ± 2,93, p = 0,0347 and t4: a) 38,38 ± 5,15h versus b) 36,05 ± 3,32h, p = 0,0152. Clinical characteristics of the donors were also analyzed: age, body mass index (BMI), total gonadotropin dose, antral follicular count (AFC), follicle stimulating hormone (FSH), basal hormone levels, follicle count, oocyte pick-up (OPU), altered oocytes, number of germinal vesicles, metaphase I (MI) and metaphase II (MII) oocytes. Differences were observed only between two clinical aspects: patients’ age: a) 24,2 ± 3,6 versus b) 25,0 ± 3,3, p = 0,0031 and OPU: a) 23,3 ± 9,1 versus b) 18,6 ± 8,3, p = 0,004, however both variables does not seem to affect embryo formation potential. Limitations, reasons for caution The results should be interpreted with caution due to the limitations of evaluate a small dataset of donors, resulting in low number of embryos in each group of protocols for analysis. Wider implications of the findings In this case-control study, a lower number of oocytes retrieved and faster early morphokinetics times were observed in PPOS compared to antagonist protocol. The implications of these differences still need further data analyses to compare if these findings can change clinical outcomes. Trial registration number Not applicable.

P-683 Progestins vs flexible GnRH antagonist for LH suppression during controlled ovarian stimulation in POSEIDON groups 3 and 4 patients: Analysis of effectiveness and cycle outcomes

Abstract Study question How do cycle outcomes differ between controlled ovarian stimulations using progestins vs flexible GnRH antagonists for LH suppression in women with diminished ovarian reserve (DOR)? Summary answer While progestin use is associated with significantly higher blastocyst rate than GnRH antagonists in POSEIDON group 4, the latter gives better results in group 3. What is known already Controlled ovarian stimulation (COS) in patients with DOR carries the additional risk of premature luteinizing hormone (LH) surge and ovulation.GnRH antagonists are popular for LH suppression in COS because of their convenient, quicker onset of action, flexibility to use GnRH agonist as a trigger and continue as double stimulation, allowing rapid pooling of embryos. Ease of oral administration, combined with cost-effectiveness and retention of all the benefits of GnRH antagonists makes progestins an attractive alternative to GnRH antagonists for COS in patients with DOR who often need multiple stimulation cycles to enable the pooling of embryos. Study design, size, duration An open-label, multicentric, randomized controlled study was conducted over 1 year from January 2023 to December 2023. 140 women aged 21- 42 years and with AMH &amp;lt;1.2 ng/dl were randomized into 2 groups in a 1:1 ratio, using either oral progestins or GnRH antagonists for LH suppression. The two groups were further comparative analyzed under POSEIDON 3 and 4 subgroups. Those with BMI &amp;gt;40kg/m2 and with partners having severely compromised semen parameters were excluded. Participants/materials, setting, methods In Group A (PPOS): Medroxyprogesterone acetate 10 mg orally was given daily with gonadotropins (hMG 300- 375 IU) from cycle day 2 until trigger. In Group B (Antagonist), patients had daily GnRH antagonist, cetrotide 0.25 mg, subcutaneous administration started when the dominant follicles reached 12-14 mm size during controlled ovarian stimulation. This was continued until the trigger. Following oocyte retrieval and ICSI, embryos were cultured until D5 and vitrified fortransfer in subsequent HRT cycles. Main results and the role of chance Patients in Group A, using PPOS, were noted to have significantly better fertilization rates than those in Group B, using flexible GnRH antagonists (0.82 + 0.2 vs 0.66 + 0.4, p-value &amp;lt;0.01). Though the number of top-quality embryos (TQE) frozen was not significantly different between groups A and B (p-value = 0.44), a significant difference in the outcome was noted when comparatively analyzed under the subgroups of POSEIDON groups 3 and 4. While patients in POSEIDON group 4 got significantly more top-quality embryos (TQE) when progestins were used for LH suppression (1 + 0.11 vs 0.77 + 0.41, p-value &amp;lt;0.01), those in POSEIDON group 3 got significantly more top-quality embryos when GnRH antagonist was used (0.94 vs 2, p-value &amp;lt;0.01). Patients in Group A and B were found to have no significant difference in the following outcomes: incidence of premature LH surge (4.3% vs 7.1%, p value= 0.71), number of days of stimulation (10.26 + 2.18 vs 10.26 +2.94, p value= 0.99), total gonadotropin dosage used (3448.64+ 1007.98 vs 3087.41 + 1260.56, p value=0.06), total number of oocytes retrieved (5.84 + 3.3 vs 4.9 + 3.4, p value=0.09) and total cycle cancellation rate (30.1% vs 35.7%, p value= 0.11). Limitations, reasons for caution The small sample size of the cases limits the current statistical power of the study. The results being encouraging need to be confirmed in a larger patient population and followed for a longer duration to enable calculation of implantation and clinical pregnancy rates for all patients. Wider implications of the findings Oral progestins are an effective and cheaper, patient-friendly alternative to injectable GnRH antagonists during COS in women with DOR. Considering the significantly higher TQEs formed, PPOS can be preferred in older, POSEIDON group 4 patients, whereas flexible GnRH antagonist protocol can be our choice in the younger, POSEIDON group 3. Trial registration number Not applicable

Use of progestogens and the risk of intracranial meningioma: national case-control study

ABSTRACTObjectiveTo assess the risk of intracranial meningioma associated with the use of selected progestogens.DesignNational case-control study.SettingFrench National Health Data System (ie, Système National des Données de Santé).ParticipantsOf 108 366 women...

Concurrent progestogen and cerclage to reduce preterm birth: a multicenter international retrospective cohort

Objective: We aimed to evaluate whether cerclage with progestogen therapy was superior to cerclage alone in the prevention of spontaneous preterm birth (sPTB) in singleton pregnancies Methods: This is an international retrospective cohort study of singleton pregnancies, without major anomaly or aneuploidy, and with cerclage placed at 10 different institutions in the United States and Colombia from June 2016-June 2020. Exclusion criteria were: lack of documentation regarding whether progestogen was or was not prescribed, delivery outcome unavailable, and pregnancy termination (spontaneous or induced) prior to 16 weeks’ gestation. Exposure of interest was progestogen use with cerclage placement, which included those who were continued on progestogen or who started progestogen after cerclage. Comparator was those without progestogen use after cerclage placement, which included those who had no progestogen use the whole pregnancy, or who initiated progestogen and then stopped it after cerclage placement. Progestogen type, cerclage indication, maternal baseline characteristics, and maternal/neonatal outcomes were collected. Primary outcome was sPTB <37 weeks. Secondary outcomes were sPTB <34 weeks, gestational age at delivery, composite neonatal outcome including ≥1 of the following: perinatal mortality, confirmed sepsis, Grade III or IV intraventricular hemorrhage, retinopathy of prematurity, respiratory distress syndrome, bronchopulmonary dysplasia. There was planned subgroup analyses by cerclage indication, progestogen type (vaginal progesterone vs 17-hydroxyprogesterone caproate (17-OHPC)), preterm birth history, and site.Continuous variables compared in adjusted analyses with ANCOVA and categorical variables compared with multivariable logistic regression adjusting for potential confounders with adjusted odds ratio (aOR). Cox regression survival curve was generated to compare latency to spontaneous delivery, censored after 37 weeks. Results: During the study period, a total of 699 singletons met inclusion, N=561 in the progestogen with cerclage group, and N=138 with cerclage alone. Baseline characteristics were similar, except those in the progestogen group were more likely to have had a prior sPTB (61% vs 41%, p<0.001). Within the progestogen group, 52% were on 17-OHPC weekly, 44% on vaginal progesterone daily, and 3% on oral progesterone daily. Progestogen with cerclage was associated with a significantly lower frequency of sPTB<37 (31% vs 39% aOR 0.59 (0.39 - 0.89), p=0.01) and <34 weeks (19% vs 27%, aOR 0.55 (0.35 - 0.87), p=0.01), increased latency to spontaneous delivery (Hazard ratio to sPTB <37wk, 0.66 (0.49-0.90), p=0.009), and lower frequency of perinatal death (7% vs 16%, aOR 0.37 (0.20-0.67), p=0.001). In planned subgroup analyses, association with reduced odds of preterm birth <37 weeks persisted in those on vaginal progesterone, those without a prior preterm birth, those with ultrasound or exam-indicated cerclage, those that started progestogen therapy prior to cerclage, and in sites restricted to the United States. Conclusion: Use of progestogen with cerclage was associated with reduced rates of sPTB and early sPTB compared to cerclage alone. Although not powered for subgroups, the strength of evidence for benefit appeared greatest for those with ultrasound or exam-indicated cerclage, and with vaginal progesterone.

Nationwide status of progestogen treatment to prevent spontaneous preterm birth: A questionnaire survey for childbirth healthcare facilities in Japan.

This study aimed to investigate the current status of progestogen treatment for pregnant women at a high risk for preterm birth (PTB) in childbirth healthcare facilities in Japan. A web-based nationwide questionnaire survey regarding progestogen use for prevention of PTB was conducted among childbirth healthcare facilities from 2019 to 2021. Valid responses were obtained from 528 facilities (25.2% of those surveyed), including 155 tertiary perinatal facilities (making up 92.3% of all tertiary perinatal care facilities). In the survey period, progestogen treatment was implemented in 207 facilities (39.2%) for PTB prevention. Regarding types of progestogens, 17α-hydroxyprogesterone caproate was used in 170 facilities (82.1%), with a low dose (125 mg/week) administered in 62.9% of the facilities to comply with the regulations of the national health insurance system, although 250 mg/week is considered the best dose. Vaginal progesterone was used in 36 facilities (17.4%), although the cost of vaginal progesterone was not covered by health insurance. Of the facilities not administering progestogen treatment, approximately 40% expressed that vaginal progesterone would be their first choice for PTB prevention in daily practice if it would be covered by health insurance in the future. Due to the current regulations of the Japanese health insurance system, 17α-hydroxyprogesterone caproate, rather than vaginal progesterone, was mainly used for PTB prevention. Despite global evidence supporting vaginal progesterone as the approach with the highest efficacy, only a limited number of facilities have utilized it due to the current drug use regulations in Japan.

Progestin-primed ovarian stimulation.

The use of progestins as pituitary suppressors has increased progressively, along with more detailed indications for their use, thereby consolidating an alternative approach to the personalization of ovarian stimulation. Based on the ability of progesterone to inhibit ovulation, progestins have been used in ovarian stimulation (OS) follicular protocols to prevent a luteinizing hormone surge in patients undergoing in vitro fertilization (IVF), as an alternative to gonadotropin-releasing hormone (GnRH) analogue administration. This review explores the different types of progestogen protocols and their efficacy depending on the type of population or reproductive procedure in which they are administered and in comparison with that of GnRH analogues. Their effect on oocytes and embryos and their safety and cost-effectiveness are also analyzed. Progestins have proven their effectiveness as a gonadotropin adjuvant in terms of ovarian response, reproductive outcome, and safety. In addition, they offer the convenience of oral administration and a lower cost than GnRH analogues. Whereas oocytes or embryos should be vitrified as it displaces the receptive period with the consequent asynchrony between embryo and endometrium. The evidence endorses progestins as a more friendly approach to OS, especially when frozen-thawed embryo transfer is planned.

Etonogestrel promotes respiratory recovery in an invivo rat model of central chemoreflex impairment.

The central CO2 chemoreflex is a vital component of respiratory control networks, providing excitatory drive during resting conditions and challenges to blood gas homeostasis. The retrotrapezoid nucleus is a crucial hub for CO2 chemosensitivity; its ablation or inhibition attenuates CO2 chemoreflexes and diminishes restful breathing. Similar phenotypes characterize certain hypoventilation syndromes, suggesting underlying retrotrapezoid nucleus impairment in these disorders. Progesterone stimulates restful breathing and CO2 chemoreflexes. However, its mechanisms and sites of actions remain unknown and the experimental use of synthetic progestins in patients and animal models have been met with mixed respiratory outcomes. We investigated whether acute or chronic administration of the progestinic drug, etonogestrel, could rescue respiratory chemoreflexes following selective lesion of the retrotrapezoid nucleus with saporin toxin. Adult female Sprague Dawley rats were grouped based on lesion size determined by the number of surviving chemosensitive neurons, and ventilatory responses were measured by whole body plethysmography. Ventilatory responses to hypercapnia (but not hypoxia) were compromised in a lesion-dependent manner. Chronic etonogestrel treatment improved CO2 chemosensitivity selectively in rats with moderate lesion, suggesting that a residual number of chemosensitive neurons are required for etonogestrel-induced CO2 chemoreflex recovery. This study provides new evidence for the use of progestins as respiratory stimulants under conditions of central hypoventilation and provides a new testable model for assessing the mechanism of action of progestins in the respiratory network.

Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis.

The use of menopausal hormone therapy (MHT) has declined due to concerns about its potential side effects. However, its pivotal role in managing postmenopausal osteoporosis is gaining increased recognition. In this article, we explore how MHT assists postmenopausal women in maintaining bone health and preventing fractures. Recent research indicates that MHT significantly reduces the risk of fractures in women. This benefit is evident regardless of a woman's bone mineral density or their use of progestogens. However, there is limited evidence suggesting that the skeletal benefits continue once the treatment is discontinued. Possible complications of MHT include heart attacks, clots, strokes, dementia, and breast cancer. The most suitable candidates for MHT are women who have recently entered menopause, are experiencing menopausal symptoms, and are below 60 years of age with a minimal baseline risk of adverse events. The treatment is available to those who meet these criteria. For women undergoing premature menopause, MHT can be considered as a means to protect bone health, especially if initiated before menopause or if accelerated bone loss is documented soon after menopause. Such decisions should be made after evaluating individual risk factors and benefits.

Exogenous Progestogen Hypersensitivity and its Increasing Association with Assisted Reproductive Techniques (ART)/in vitro Fertilization (IVF).

Progestogen hypersensitivity (PH) also known as autoimmune progesterone dermatitis is a rare clinical entity that may be triggered by endogenous progesterone (menstrual cycles and pregnancy) or exogenous progestin exposure (examples: contraceptive medicines, in vitro fertilization treatments). It is a poorly recognized syndrome due to its heterogeneous clinical presentation. The pathomechanism of PH is believed to be primarily IgE mediated but less commonly other immune responses may be involved. Management is usually focused on symptomatic control with medications. Recently, with the increasing use of exogenous progestins for in vitro fertilization more cases of hypersensitivity to exogenous progestins have been reported. Progesterone is an essential drug in the luteal phase support improving chances of implantation and pregnancy rates, and hence, PH is an important and difficult challenge to manage in these patients. Because patients require IVF and there is no alternative to progesterone, desensitization is suggested as an approach to endure fertility treatments and provides symptom control in refractory cases. Here, we will review the different aspects of PH.

FRI413 Hormonal Menstural Suppression For Menstrual Obstruction: A Retrospective Review Of Patients With Complex Obstructed Uterovaginal Anomalies Who Underwent Surgical Management In A Tertiary Referral Centre

Abstract Disclosure: H.I. Learner: None. S.M. Creighton: None. S.A. Clarke: None. Aims: To describe the use of hormonal menstrual suppression in patients undergoing surgery for complex utero-vaginal anomalies with menstrual obstruction. Background: Obstructed menstruation can present with painful primary amenorrhea or progressive dysmenorrhea due to unilateral obstructing duplication utero-vaginal anomalies. Menstrual suppression is essential to relieve pain during investigation and surgical planning. The off licence use of progestogens, hormonal contraception and GNRH analogues is common but there is little literature describing their best use in this context. Methods: This was a retrospective case series review of patients undergoing surgical management of complex menstrual obstruction in a tertiary referral centre between 2016-2022. Data collected on age, diagnosis, symptoms, duration of symptoms, surgery, the type of endometrial suppression used and associated side effects.Patients with partial obstruction were excluded. Results: Eighty-four patients were identified from the surgical database. The median age at time of surgery was 16 years (range 11-36). Unilateral obstruction was managed in 53/84 and complete obstruction in 31/84. Diagnoses included obstructed hemi-vagina (32/84), unicornuate uterus with functional uterine remnant (19/84), transverse vaginal septum (15/84), cervical/vaginal agenesis (9/84), and Mullerian agenesis with functional uterine remnant (5/84). Symptom duration information was available in 74/84 with a median of 10 months(0-252 months). Changes to endometrial suppression treatment were required in most patients, with 50/84 (40%) remaining on their original prescription. The average number of treatment regimes was 2 (0-7). Menstrual suppression at time of surgery was Norethisterone 35/84 (42%), Continuous combined oral contraceptive pill18/84 (21%), Medroxyprogesterone 11/84 (13%), GNRH 10/84 (12%), Desogestrel 6/84 (7%), and Depo-Provera 4/84 (5%). Tibolone was used as add-back in five patients on GNRHa for more than 6 months duration of use (4/5) or hypoestrogenic side-effects (1/5) . Conclusion Menstrual suppression for pain relief is an essential component in management for complex uterovaginal anomalies. Suppression should be started at initial presentation but there is limited guidance for clinicians as to what and how to prescribe. Our study has demonstrated that this can lead to chaotic prescribing, unnecessary pain and multiple treatment changes. Presentation: Friday, June 16, 2023

Предикторы рецидивирующего течения эндометриальной гиперплазии без атипии у женщин репродуктивного возраста

Aim. To establish predictors of recurrent course of endometrial hyperplasia (EH) without atypia in women of reproductive age. Material and methods. A retrospective analysis of 180 patients of reproductive age was performed on the basis of the Department of Obstet-rics and Gynecology with a course of perinatology at the Patrice Lumumba Peoples' Friendship University of Russia in Semashko Clinical Hospital "RZD-Medicine" in 2020–2023. During the study, two cohorts of patients were formed depending on the course of EH: group 1 – the main group (n=95) was represented by patients with morphologically verified recurrent EH without atypia during a year of follow-up (1 or more episodes of relapse), group 2 – comparison (n=85) – patients with morphologically verified EH without a history of atypia, with no recurrence of hyperplasia during the year. The average age of patients in the studied cohort was 43±3.0 years (comparison groups – 40±2.0 years). Results. In a cohort of patients suffering from morphologically confirmed recurrent EH without atypia, a high incidence of the following predic-tors was established during the year: refusal/absence of medication in the anamnesis – 32.2%, duration of therapy (less than 6 months) – 23.2%, cyclic mode of progestogen use (from the 14th to the 26th day of menstrual cycle – MC/from 16 on the 26th day of the MC) – 15.8%. Patients with recurrent EH were significantly more likely to be obese in 45.3%, arterial hypertension – 38.9%, severe vitamin D deficiency – 32.6%, vitamin D deficiency – 40%, chronic endometritis – 41.1%. Conclusion. Predictors of recurrent course of EH without atypia in women of reproductive age are: refusal/absence of taking medication in anamnesis (odds ratio – OR 39.909; 95% confidence interval – CI 4.899–278.068), duration of therapy less than 6 months (OR 12.507; 95% CI 2.843–55.015), cyclic mode of progestogen use – from the 14th to the 26th day of the MC/from the 16th to the 26th day of the MC (OR 8.893; 95% CI 1.966–40.229). Patients with recurrent EH were significantly more likely to have severe vitamin D deficiency (OR 13.466; 95% CI 5.323–34.068), chronic endometritis (OR 4.237; 95% CI 2.032–8.833), hypertension (OR 3.881; 95% CI 1.858–8.801), obesity (OR 2.368; 95% CI 1.259–4.453), vitamin D deficiency (OR 1.574; 95% CI 0.814–3.045). Prevention of non-atypical hyperplasia with progestogens and lifestyle mod-ification carries a wide range of benefits, including those associated with a favorable fertility prognosis.

Modern approaches to the correction of age-related skin changes in women

The article is devoted to the literature review on the correction of age-related skin changes in women. Skin aging is a physiological process that is caused by the constant action of unmodified factors, for example, endocrine disorders, shortening of telomeres, etc., in combination with periodic influence of modified (exposomal) factors. Ultraviolet radiation takes first place among external factors affecting the progression of degenerative changes in skin, however, in women, involutional changes in skin are primarily associated with a fading of synthetic function of ovaries. During the first five years from the onset of menopause, content of collagen fibers I and III types is reduced by 30% in combination with a further reduction of 2% annually for the next 15 years.Involutive transformations occur in all layers of skin and are visually characterized by the presence of wrinkles, roughness of the epidermal surface (with photoaging) or a decrease in its thickness (with chronic aging), dryness, pigmentation disorders in the form of uneven hyperpigmented spots, telangiectasias, oval deformations.Today, there are many methods of aesthetic correction of age-related skin changes. In the arsenal of a cosmetologist there are both invasive (PRP-therapy, microneedling, microneedle radio wave lifting, administration of preparations based on calcium hydroxyapatite, polylactic and hyaluronic acid, etc.) and minimally invasive (administration of botulinum neuroprotein, application of chemical acid peelings, IPL-therapy and laser polishing, photodynamic therapy) methods. Patients prefer minimally traumatic procedures due to the fact that they almost do not disturb the processes of socialization, however, each of these methods has both advantages and disadvantages.Modification of a woman life quality in peri- and menopause in form of changes in lifestyle and eating behavior, increasing physical activity, quitting smoking and limiting the use of alcoholic beverages is an integral part of therapeutic care. However, the appointment of menopausal hormonal therapy, including the use of estrogens, progestogens and combined hormonal drugs, allows to achieve a stable and long-lasting effect from cosmetology procedures and home care.

The association between menopausal hormone therapy and gastroesophageal reflux disease: a systematic review and meta-analysis.

Gastroesophageal reflux disease (GERD) is a chronic condition associated with several risk factors, but little is known about the association between hormone therapy (HT) and GERD in postmenopausal women. We investigated the association between ever or current menopausal HT use and GERD using a systematic review and meta-analysis. Studies published between 2008 and August 31, 2022, were pooled using a DerSimonian and Laird random-effects model, and outcomes were reported as adjusted odds ratios (aOR) with a corresponding 95% CI. The pooled analysis of five studies found a significant direct association between estrogen use and GERD (aOR, 1.41; 95% CI, 1.16-1.66; I2 = 97.6%), and progestogen use and GERD (two studies: aOR, 1.39; 95% CI, 1.15-1.64; I2 = 0.0%). The use of combined HT was also associated with GERD (1.16; 95% CI, 1.00-1.33; I2 = 87.9%). Overall, HT use was associated with 29% higher odds for GERD (aOR, 1.29; 95% CI, 1.17-1.42; I2 = 94.8%). The large number of pooled participants, differences in study design, geography, patient characteristics, and outcome assessment resulted in significant high heterogeneity. There is a significant association between ever or current HT use and GERD. However, the results should be interpreted with caution, given the small number of included studies and high heterogeneity. This warrants careful evaluation of GERD risk factors when prescribing HT to reduce the risk of potential GERD complications.

Progestins and combined oral contraceptives in the hormonal treatment of endometriosis – a review

Introduction and aim. Endometriosis is a common inflammatory disease affecting 6-10% of women of reproductive age. It is defined as the growth of endometrial-like tissue outside the uterine cavity. Dysmenorrhea, pelvic pain, dyspareunia and infertility are the main symptoms of endometriosis patients. Endometriosis treatment methods can be broadly divided into surgical and pharmacological. Currently, hormonal drugs are often used for women with endometriosis to relieve bothersome symptoms. The aim of this article is to review new publications presenting the effectiveness as well as side effects of the use of progestins and combined oral contraceptives in the hormonal treatment of endometriosis. Material and methods. A review of the literature regarding progestins and combined oral contraceptives in the treatment of endometriosis was performed using the PubMed database. In the end, 67 articles were included in this review. Analysis of the literature. Progestins and combined oral contraceptives significantly reduce dysmenorrhea, dyspareunia and pelvic pain in women with endometriosis. However, there is a risk of potential side effects, which should be taken into account when choosing a therapy for each patient individually. Conclusion. Endometriosis is a chronic disease that has a significant impact on the health-related quality of life of patients. When choosing a treatment, many aspects should be considered, primarily the patient’s preferences, drug tolerance and safety. Further drug research is needed to determine the most effective treatment for endometriosis.