Synthetic Progestin Research Articles

Onset and recovery from depressive mood changes on progestin treatment - a case series reporting the course and type of depressive symptoms in progestin users with different histories and risks

Objective Progestin-only contraceptives are commonly used in women with contraindications for the use of combined hormonal contraception. They are also important treatment options for medical conditions like endometriosis. Although it is well known that progestins may have a negative impact on mood, little is known on how to identify women at risk and the course of such an adverse event after discontinuation. This case series aimed to evaluate the onset and reversibility of depressive symptoms, as well as potential risk factors for the development of mood problems in new-starters of progestins. Methods Case series of patients, who reported symptoms of depression after initiating use of a synthetic progestin. Results Seven women reported depressive symptoms after newstart with desogestrel, dienogest or the LNG-IUS 52 mg. Symptom onset was within 3 months in six cases. One woman reported a family history of depression. In all users symptoms resolved soon after discontinuation. Three patients had experienced mood problems with another progestin in the past. After symptoms had resolved two patients tolerated another progestin method. Conclusion Depressive symptoms after newstart of a progestin came up soon. It is promising that symptoms resolved within few weeks after discontinuation. Close follow-up of all newstarters is recommended.

GLOBAL USE OF ETONOGESTREL IMPLANTS IN ZOO-HOUSED ANIMALS.

Hormonal contraception is often used by zoos and aquaria to manage genetic diversity and the size of their populations. However, the contraceptive products used have typically not been designed for use in the target species. The Association of Zoos and Aquariums' Reproductive Management Center (AZA RMC) and the European Association of Zoos and Aquaria's Reproductive Management Group (EAZA RMG) collect data on contraceptive use in global zoos and aquaria to monitor trends and generate contraceptive recommendations. The human 68 mg etonogestrel contraceptive implant (Implanon®/Nexplanon®/Implanon NXT®), a synthetic progestin, has three contraceptive mechanisms: preventing luteinizing hormone release and therefore ovulation, thickening of the cervical mucus, limiting the entry of sperm, and modification of the uterine lining, inhibiting implantation. Here, we review over 30 years of data from the Reproductive Management Center-Reproductive Management Group Contraception Database (CD; N = 3,510 records). Etonogestrel implant use has only been reported in mammals in the CD, including nonhuman primates (91.34% of records), chiropterans (5.78%), carnivores (1.05%), and other mammals (1.82%). The implants are highly effective when used as contraceptives (98.14% effective), and two-thirds of implant failures are attributable to implant loss or to the incorrect application of the product, rather than to true product failures. Etonogestrel implants are generally safe, although long-term use in carnivores is discouraged due to risks of developing reproductive pathology resulting from long-term progestin exposure. Reported noncontraceptive effects included weight gain and a reduction in sexual behavior, which are known noncontraceptive effects in humans. Etonogestrel implants are generally reversible as 63.09% of individuals given the opportunity to breed produced offspring. Etonogestrel implants are safe and effective contraceptives in most female mammals. Further research on noncontraceptive effects and reversibility is required to finetune management recommendations.

O-244 Progestogens versus GnRH analogue protocols for prevention of LH surge in women undergoing ART: A systematic review and meta-analysis

Abstract Study question Does prevention of endogenous LH surge using progestogens lead to similar live birth rates after the first embryo transfer(ET) when compared to GnRH analogue protocols? Summary answer Prevention of endogenous LH surge using progestogens lead to similar live birth rates after the first ET when compared to GnRH analogue protocols. What is known already Ovarian stimulation with progestogens has emerged as an innovative strategy to inhibit endogenous luteinizing hormone (LH) surge during ovarian stimulation. Progestogens, encompassing both natural progesterone and synthetic progestins, suppress gonadotropin-releasing hormone (GnRH) secretion, effectively preventing LH surge. This oral administration offers a less invasive and more cost-efficient alternative to conventional protocols using GnRH analogues. Relevant randomized controlled trials (RCTs) have produced inconsistent results regarding the efficacy of these methods, leading to uncertainty on whether the likelihood of achieving a live birth following the first ET is comparable between the two approaches. Study design, size, duration A systematic literature search, following a predefined protocol, was conducted in MEDLINE, Embase, and CENTRAL until January 2025 to identify eligible RCTs. Two reviewers independently screened results and extracted demographic, methodological, and clinical data. The primary outcome was live birth after the first ET; secondary outcomes included clinical pregnancy, ongoing pregnancy rates and ovarian stimulation outcomes. Study quality was assessed using RoB2 and TRACT tools to evaluate risk of bias and trustworthiness, respectively. Participants/materials, setting, methods Twelve eligible RCTs (published between 2019–2024), including 2677 women undergoing ART, were identified. The intervention group received medroxyprogesterone acetate (MPA), dydrogesterone (DYG), or micronized progesterone, while GnRH analogues (agonist or antagonist) were used as a comparator. For dichotomous outcomes, results were expressed as risk ratios (RR) with 95% confidence intervals (CIs), using fixed- or random-effects models. For continuous outcomes, pooled differences were calculated as weighted mean differences (WMD) with 95% CIs. Main results and the role of chance No statistically significant differences were present between women undergoing ovarian stimulation with progestogens and those using GnRH analogue protocols regarding ovarian stimulation duration (WMD: -0.02 days, 95% CI -0.49 to + 0.45, I2=75.7%, random-effects model,7 studies, n = 1367), the total gonadotropin dose required (WMD: +44.84 IU, 95% CI -45.59 to + 135.26, I2=57.9%,random-effects model,7 studies, n = 1367),cumulus-oocyte complexes (COCs) retrieved (WMD: +0.38 COCs, 95% CI -0.03 to + 0.79, I2=48%, fixed-effects model, 7 studies, n = 1367) and two-pronuclear (2pn) oocytes (WMD: -0.20 2pn oocytes, 95% CI -2.01 to + 1.60, I2=71.2%,random-effects model, 3 studies, n = 580). In addition, no statistically significant differences were observed following the first ET in live birth (RR: 0.98, 95% CI 0.75–1.28, I2=62.1%,random-effects model, 4 studies, n = 1024), ongoing pregnancy (RR: 0.85, 95% CI 0.52–1.37 I2=84.9%,random-effects model,2 studies, n = 336) clinical pregnancy (RR: 0.93, 95% CI 0.68–1.27, I2= 73.9%, random-effects model,4 studies, n = 752) and miscarriage rates (RR: 0.96, 95% CI 0.56–1.64 , I2=0%, fixed-effects model,4 studies, n = 656). All of the studies were considered trustworthy by applying TRACT checklist. One study was of high risk of bias and was excluded in the sensitivity analysis, which did not materially alter the results observed. Limitations, reasons for caution Moderate clinical heterogeneity was observed across studies comparing progestogen and GnRH analogue protocol regarding the type of progestogen used. Meaningful exploration of this heterogeneity was not possible due to the limited number of studies. Wider implications of the findings Since the prevention of endogenous LH surge using progestogens results in comparable live birth rates after the first ET to those achieved with GnRH analogue protocols, it represents an appealing option for cycles where fresh embryo transfer is not planned. Trial registration number No

Comparative Study of Levonogystril (Oral Contraceptive) with Solanum Khasianum

The rising demand for safe, effective, and accessible contraceptive methods has led to comparative investigations between synthetic and herbal agents. Levonorgestrel, a synthetic progestin commonly used in emergency and oral contraceptives, is well-established for its potent ovulationinhibiting effects and high efficacy. However, prolonged use is often associated with side effects such as nausea, menstrual irregularities, and hormonal imbalances. In contrast, Solanum khasianum, a medicinal plant belonging to the Solanaceae family, contains steroidal alkaloids— particularly solasodine—which serve as precursors for the synthesis of steroidal contraceptives. This study aims to compare the contraceptive potential, mechanism of action, and safety profiles of levonorgestrel and Solanum khasianum extracts. Pharmacological evaluation was conducted using both in vitro and in vivo models to assess ovulation inhibition, endometrial changes, and hormonal modulation. Results demonstrated that Solanum khasianum exhibited significant antifertility activity through suppression of follicular maturation and alteration of the estrous cycle, albeit to a lesser degree than levonorgestrel. However, the herbal extract showed a lower incidence of systemic side effects and better biocompatibility. The study concludes that while levonorgestrel remains more potent and reliable for immediate contraception, Solanum khasianum holds promising potential as a natural alternative for long-term fertility regulation, especially in populations favoring herbal medicine. This comparative analysis emphasizes the importance of integrating herbal alternatives into reproductive health research, encouraging further investigation into formulation standardization, dose optimization, and long-term safety of Solanum khasianumbased contraceptive solutions.

Different Progestins Alter Transcriptional Expression of primiR-190 and primiR-199a-1 in T47D Breast Cancer Cells

Background: Breast cancer accounts for 30% of all new cancers diagnosed in women annually. Current evidence shows that 70-80% of newly diagnosed breast cancers are hormone sensitive, indicating that their growth is promoted by hormones such as progestins and estrogens. Progestins have been found to alter microRNA expression in cancer and various tissues in humans, potentially contributing to breast cancer progression and metastasis. Different progestins regulate specific microRNAs known to influence genes that promote cancer development and growth. Our initial computer-based analysis identified primiR-190 and primiR-199a-1 as potential targets for CD44 and vascular endothelial growth factor (VEGF), proteins essential in breast cancer growth. This study determined the effect of different progestins on transcriptional expression of primiR-190 and primiR-199a-1 in T47D breast cancer cells. Methods: Progesterone receptor (PR)-positive T47D breast cancer cells were exposed to the natural hormone, progesterone, and three synthetic progestins, medroxyprogesterone acetate, norgesterol, and norethindrone for 24 hours. Real-time PCR was used to determine the transcriptional expression of primiR-190 and primiR-199a-1. To confirm the role of PR-dependent pathways on expression of both primiR-190 and primiR-199a-1, we also tested the different progestins on a progesterone receptor (PR) negative cell line, T47Dco-Y. Results: Our results showed significantly increased transcriptional expression of primiR-190 and primiR-199a-1 in T47D breast cancer cells when exposed to progesterone and synthetic progestins. RU-486, a PR antagonist, suppressed progestin-induced expression of both primiR-190 and primiR-199a-1. We did not observe progestin-induced effects in the PR-negative cell line. These results suggest a direct involvement of PR-dependent pathways in regulation of these two microRNAs. This study also found no effect on expression of primiR-190 and primiR-199a-1 when T47D cells were exposed to 17β estradiol and DMSO providing further evidence that progestins exclusively regulate expression of these two microRNAs. Conclusion: We concluded that different progestins significantly increase transcriptional expression of primiR-190 and primiR-199a-1 through progesterone receptor-mediated pathways. Our results indicate that primiR-190 and primiR-199a-1 expression can be useful as biomarkers in some forms of PR-positive breast cancers. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Variations in melasma risk associated with different synthetic progestins: A population-based analysis of TriNetX.

Variations in melasma risk associated with different synthetic progestins: A population-based analysis of TriNetX.

Dienogest vs. combined oral contraceptive: A systematic review and meta-analysis of efficacy and side effects to inform evidence-based guidelines.

Dienogest is a synthetic fourth-generation progestin that has been approved for the medical treatment of endometriosis, and its efficacy on pain symptoms and quality of life is well established even in the long term. Nowadays, only a few controlled trials evaluating the safety of dienogest compared with other hormonal therapies have been published. This systematic review and meta-analysis aims to compare efficacy and tolerability data between dienogest and combined oral contraceptives (COC) in patients taking hormonal therapy for endometriosis treatment in order to inform evidence-based guidelines. PubMed (Medline), Web of Science, and Google Scholar were systematically searched from the inception of each database until October 2024. Selection criteria included any articles comparing efficacy outcomes and at least one tolerability data between dienogest and COC in patients diagnosed with endometriosis. Studies comparing COC containing Dienogest or another type of hormonal treatment were excluded. A random-effects meta-analysis was conducted if adequate data were available from at least three studies, reporting pooled mean differences and odds ratios between groups using Review Manager V.7.9.0. PROSPERO registration number: CRD42024598455. A total of four randomized control trials and one observational study were included, showing moderate risk at bias assessment. Meta-analysis did not show any statistical difference in improving pelvic pain after treatment [CI 95% (-1.45-1.17); I2 = 86%; p = 0.84]. In contrast, dyspareunia after treatment was significantly lower in the COC group [CI 95% (0.64-1.33); I2 = 0%; p < 0.00001]. No statistical difference was found in terms of vaginal bleeding [OR = 0.88; CI 95% (0.39-1.96); I2 = 41%; p = 0.75], nausea and vomiting [OR = 0.51; CI 95% (0.16-1.63); I2 = 67%; p = 0.26], headache [OR = 0.91; CI 95% (0.38-2.21); I2 = 59%; p = 0.84], hot flushes [OR = 1.16; CI 95% (0.54-2.48); I2 = 0%; p = 0.71], and hair loss [OR = 1.69; CI 95% (0.52-5.53); I2 = 46%; p = 0.39]. Treatment discontinuation rate was similar between groups. Dienogest is comparable to COC in terms of efficacy and tolerability. The therapeutic choice should be based on the patient's preference, clinical history, and experience.

In utero exposure to synthetic sex hormones and their multigenerational impact on neurodevelopmental disorders: Endocrine disruptors as neuroendocrine disruptors.

In utero exposure to synthetic sex hormones and their multigenerational impact on neurodevelopmental disorders: Endocrine disruptors as neuroendocrine disruptors.

Self-reported hormonal contraceptive use in the British Armed Forces.

Hormonal contraceptives contain synthetic oestrogens and/or progestogens that can alter the endogenous production of oestradiol and progesterone, which potentially affect aspects of health and performance important for military employment. The nature of military service-operating away from home for prolonged periods, often in austere environments-might influence the choice of hormonal contraceptives of servicewomen. Hormonal contraceptive use and the primary reasons for use in British servicewomen are poorly understood. All trained servicewomen in the UK Armed Forces (N=14 500) with an active email were invited to respond to an online questionnaire. The questionnaire asked about demographics, current hormonal contraceptive use and reasons for choosing to use hormonal contraceptives. The survey was open for 3 months. A total of 3395 servicewomen completed the questionnaire (23% response rate). Hormonal contraceptives were currently used by 58% of servicewomen. The most common methods were the contraceptive pill (20% of all respondents) and the intrauterine system (17%). The main reasons for using hormonal contraceptives were to prevent pregnancy (78%) and to control or stop the menstrual cycle (61%). A high proportion of UK servicewomen use hormonal contraceptives, particularly younger women, with the contraceptive pill the most popular method. The high proportion of women using hormonal contraceptives to control or stop menstrual bleeding is likely determined by the unique cultural and environmental barriers of military employment.

Abstract 6165: Antiprogestin- mediated endocrine therapy activates immunotherapy- responsive programs in hormone receptor positive breast tumors

Abstract The endocrine status of the patient is a critical factor that may modulate the immune response in breast cancer and, accordingly, should be considered during immunotherapy regimens. Given the immunosuppressive and tolerogenic activities of the sexual hormone progesterone and its roles in promoting breast cancer initiation, we aim to evaluate the effect of the antagonist of the classical progesterone receptor, Mifepristone (MIFE), as an endocrine therapy to alter the tumor microenvironment, and particularly to shape an immunogenic and immunotherapy-responsive profile. We evaluated the breast tumor immune landscape both in a mouse model of luminal tumors (C4HD) treated with a synthetic progestin MPA and with MIFE; and in human tumor samples derived from the MIPRA clinical trial (NCT02651844), where breast cancer patients harbouring HR+ tumors were treated with MFP for 14 days before surgery. Using RNA-seq, bioinformatics tools and flow cytometry, we interrogated the C4HD tumor immune infiltration profile after MPA and MIFE treatment, including several global gene expression signatures associated with T-cell exclusion and Immune Checkpoint Inhibitors (ICI) sensitivity and resistance. We observed that treatment with MFP in HR+ luminal breast tumors restrains the progestin-mediated tolerogenic infiltrate composed of Tregs, exhausted CD8+ T cells and TAM macrophages. Importantly, MIFE downregulates the suppressive pathway of IDO, CXCL5, VEGF and Galectin-9, which in turn contributes to the persistence of a population of CD8+ T cells that highly produce granzymes and express lower TIM-3 and PD-1, exhibiting a reinvigorating phenotype. On the contrary, MIFE treatment upregulated several immune-associated genes such as chemokines, granzymes, ICOS-L, EOMES, CD86, CD8 and PD-L1. More importantly, we showed that in both mouse models and human tumors, treatment with MIFE reverts transcriptional signatures associated with T cell exclusion and ICI resistance and significantly upregulates programs associated with immunogenic cell death and PD-1/PD-L1 treatment response. To summarize, our results demonstrate that endocrine therapy as MIFE can foster in HR+ tumors a complete remodelling of the immune landscape, promoting immune cell infiltration and immunogenicity. As a result of the neoadjuvant MIFE treatment, HR+ luminal tumors that traditionally were considered “cold” tumors are now heavily enriched with an immunogenic PD-L1-expressing infiltrate, thus opening a new window of treatment opportunity that may sensitize luminal breast tumors to ICI. Citation Format: Mariana Salatino, Joaquin Pedro Merlo, Tomas Dalotto-Moreno, Magalí Bertón, Ramiro Martin Perrotta, Andres Elia, Karina V. Mariño, Claudia M. Lanari, Gabriel A. Rabinovich. Antiprogestin- mediated endocrine therapy activates immunotherapy- responsive programs in hormone receptor positive breast tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6165.

Cortisol prevents the suppressive effect of LPS on bovine oocyte maturation in vitro

During the periovulatory period, local production of cortisol surges in the bovine cumulus-oocyte complex (COC), although its physiological significance is not well understood. As a potentanti-inflammatory agent, cortisol may protect the COC from inflammation caused by lipopolysaccharide (LPS), an endotoxin known to cause infertility in postpartum cows. This study examinedthe effect of cortisol, together with progesterone (P4), on LPS-challenged bovine oocyte maturation. COCs were aspirated from follicles 2–5 mm in diameter and subjected to invitro maturation for 21 h with various combinations of LPS, cortisol, cortisone (a substrate for cortisol production), trilostane (a P4 synthesis inhibitor), and nomegestrolacetate (NA; a synthetic progestogen). LPS (0.001, 0.01, 0.1, 1 μg/ml) suppressed oocyte maturation in a dose-dependent manner, and this effect was reversed by concomitant treatment withcortisol (0.1 μM). COCs converted cortisone to cortisol, and the locally produced cortisol (approximately 0.01 μM) was capable of negating the suppressive effect of LPS (1 μg/ml) on oocytematuration. Trilostane suppressed oocyte maturation by eliminating P4 production, indicating the crucial role of P4 in this process. LPS equally suppressed oocyte maturation, regardless ofthe presence or absence of P4 or the various doses of NA (0.001–1 μM). This suggests that P4 alone does not inhibit the action of LPS. However, in the absence of P4, cortisol could notsuppress the LPS effect on oocyte maturation. Collectively, these findings suggest that the bovine COC can protect itself from the suppressive effects of LPS by producing cortisol, with P4being essential for this function.

Features of the use of combined oral contraceptives for the correction of premenstrual syndrome

Annotation. Premenstrual syndrome (PMS) is a set of cognitive, physical, and affective symptoms that occur during the luteal phase of the menstrual cycle and disappear at the beginning of menstruation. Its more severe variant is premenstrual dysphoric disorder (PMDD). The aim of the work is to investigate the effects of combined oral contraceptives and their effectiveness and safety for the correction of PMS and PMDD. A retrospective analysis of the scientific literature was carried out using the following sources: PubMed, ReseachGate, Science Direct, Web of Science, Cochrane. The majority of publications published in the last five years (2019-2024) were selected for the study. Both syndromes are believed to be caused by cyclical changes in progesterone production. Combined oral contraceptives (COCs) are considered one of the treatment options for PMS and PMDD, as the drugs of this group contain synthetic estradiol and progestin, which have a complex effect on the hypothalamic-pituitary-ovarian system.

Progestin Pollution in Surface Waters of a Major Southwestern European Estuary: The Douro River Estuary (Iberian Peninsula).

The concentrations and spreading of eight synthetic and two natural progestins (PGs) were investigated in surface waters from ten sites at the Douro River Estuary. Samples were filtrated and subjected to solid-phase extraction (SPE) to isolate and concentrate the target PGs. The extracts were cleaned by silica cartridges and analyzed by LC-MS/MS. The finding of biologically relevant amounts of gonanes (22.3 ± 2.7 ng/L), progesterone derivatives (12.2 ± 0.5 ng/L), drospirenone (4.1 ± 0.8 ng/L), and natural PGs (9.4 ± 0.9 ng/L) support the possibility of these compounds acting as endocrine disruptors. Despite the absence of significant differences amongst sampling sites and seasons, the principal component analysis (PCA) and the linear discriminant analysis (LDA) approaches reveal that spring and summer have different patterns of PG distribution compared to autumn and winter. The assessment of risk coefficients (RQs) and the potential concentrations of synthetic progestins in fish blood sustains that all tested compounds pose a significant risk to local biota (RQs > 1). Additionally, three progestins-norethindrone, norethindrone acetate, and medroxyprogesterone acetate-should reach human-equivalent therapeutic levels in fish plasma. Overall, the current data show PGs' presence and potential impacts in one of the most important estuaries of the Iberian Peninsula.

The effect of norethisterone acetate on the uterine telocytes, immune cells and progesterone receptors in albino rats

This study is the first attempt to examine the effects of NETA on immune cells and telocytes. The results of this study form an important knowledge base for the development of new information on the mechanism of contraceptive action of NETA in the uterus. Norethisterone acetate (NETA) is a synthetic progestogen medication commonly utilized in birth control pills, menopausal hormone therapy, and for curing abnormal uterine bleeding and endometriosis. Furthermore NETA has many beneficial uses in veterinary medicine as control and synchronization of estrous cycle. The impact of NETA on the endometrial stromal cells (ESCs), telocytes, and uterine immune cells is not well understood. Therefore, this study focuses on assessing changes in uterine immune cells, ESCs, and telocytes following exposure to NETA in albino rats. To achieve this objective, fourteen adult female albino rats were randomly divided into two groups: a control group and an NETA-treated group. Rats in the control group received daily pelleted food, water, and were oral administered of 2 ml distilled water. In contrast, rats in the NETA-treated group received daily pelleted food, water, and were orally administered 20 µg of NETA dissolved in 2 ml distilled water. The experiment spanned three weeks. The findings of this study revealed that NETA usage increases the infiltration and activity of immune cells (eosinophils, neutrophils, macrophages, lymphocytes, and mast cells). Furthermore, it enhances the vesicular activity of uterine telocytes and their communication with various immune cells. NETA also influences decidualization and the immunoexpression of progesterone receptors in uterine epithelial and immune cells. This study concludes that the primary mechanism by which NETA controls pregnancy is through decidual (pregnancy-like) effects or improper decidualization, which inhibits fertilization and implantation respectively. Our research provides evidence of the contraceptive mechanism of NETA from an immunological perspective in an animal model.

Natural and Synthetic Progestins Increase Transcriptional Expression of primiR-190 and primiR-199 in T47D Breast Cancer Cells: A Preliminary Study.

Background Previous studies have shown that aberrant expression of different microRNAs potentially contributes to carcinogenesis, growth, and metastasis of several human cancers. Given that progestins have been reported to alter the expression of microRNAs in various human cancers, we hypothesized that progestins potentially influence the growth of hormone-responsive breast cancer through mechanisms involving the regulation of miRNAs functioning either as tumor suppressors or oncogenes. Using computer-based analysis, we identified two microRNAs that we investigated in this study, namely miR-190 and miR-199. Our main objective in this preliminary study was to determine the effect of different progestins on the expression of these two microRNAs in breast cancer cells. Methods Progesterone receptor (PR)-positive cell line, T47D breast cancer cells were exposed to progesterone and three different synthetic progestins for 24 hours, after which RNA was extracted and real-time polymerase chain reaction (PCR) was used to determine the expression of primiR-190 and primiR-199. For comparison, progestin effects were also tested in T47Dco-Y, a PR-negative cell line. Results Our results showed exposing T47D cells toboth progesterone and synthetic progestins increased the transcriptional expression of primiR-190 and primiR-199a1 by as high as four to seven fold (P<0.0001). RU-486, a progesterone receptor antagonist, suppressed progestin induction of both primiR-190 and primiR-199a1. Progestin-induced effects were not observed in a PR-negative subline of T47D cells (P>0.05), further confirming the involvement of progesterone receptor-dependent pathways. Additionally, 17β estradiol and dimethyl sulfoxide did not alter the expression of both primiR-190 and primiR-199a1. Conclusion Different progestins increase transcriptional expression of both primiR-190 and primiR-199a-1 through progesterone receptor (PR)-dependent mechanisms. Both primiR-190 and primiR-199a1 can potentially be useful as biomarkers for PR-positive breast cancer.

A REVIEW STUDY ON SMALL DIFFERENTIATIVE BETWEEN ORAL CONTRACEPTIVES (PROGESTIN-ONLY PILLS/ COMBINED HORMONAL PILLS)

Oral contraceptive pills, are commonly used drugs to manage a number of reproductive health issues and prevent unwanted births. They are divided into two main categories: progestin-only pills (POPs) and combined oral contraceptives (COCs), which contain synthetic estrogen and progestin. In order to stop conception and implantation, COCs mainly function by suppressing ovulation, thickening cervical mucus, and changing the endometrial lining.Numerous people utilize contraceptives; according to 2019 statistics, 790 million (42%) use the traditional technique. The most popular methods of birth control are female sterilization and male condoms, which are used by 922 million women of reproductive age worldwide. According to 2019 data, 219 million of these women (24%), and 189 million of them (21%), use female sterilization and male condoms, respectively. Since 1994, the use of IUDs and conventional procedures has decreased globally. The WHO states that the condom is the only method of birth control that can prevent both unwanted pregnancies and STDs. Between 2015 and 2020, the need for family planning increased by 77% worldwide. In 2020, there will be 2000 million women who have used family planning methods, up from 900 million in the previous 20 years. The number of people using modern contraceptive techniques has likewise climbed from 663 million to 851 million, with a 47.7% to 49.0% prevalence rate. Numerous types of birth control are available, including hormonal treatments, which include CHC vaginal rings, CHC transdermal patches, and combination hormonal contraceptives. IUDs with progestin, DMPA injections, implants, progestin-only pills, and hormonal male contraceptives are examples of progestin-only techniques. The other approach is non-hormonal and involves vaginal pH modulators, barrier techniques like condoms, and copper IUDs.

Safety evaluation of medroxyprogesterone acetate: a pharmacovigilance analysis using FDA adverse event reporting system data.

Medroxyprogesterone acetate (MPA), a synthetic progestogen, is extensively used for the treatment of various conditions, including contraception, irregular menstruation, functional uterine bleeding, and endometriosis. However, like all pharmaceutical agents, MPA is associated with adverse drug reactions. This study aimed to evaluate the adverse events (AEs) associated with MPA in by analyzing real-world data from the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS). By providing a comprehensive assessment of the safety profile of MPA, this study seeks to support informed clinical decision-making. Data covering the period from the first quarter of 2004 to the first quarter of 2024 were collected from the FAERS database. Disproportionality analyses were conducted using several statistical methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), empirical Bayesian geometric mean (EBGM). Additionally, time-to-onset (TTO) analysis was employed to quantify the signals of the MPA-associated AEs. A comprehensive dataset comprising 21,035,995 AE reports was compiled. Among these, 3,939 women reported using MPA as a contraceptive method. The reports covered 27 system organ classes (SOCs) and 25 high-frequency AE signals. Notably, significant AEs were identified, some of which were not previously detailed in the medication's prescribing information. Unforeseen significant AEs such as unintended pregnancy (n = 623; ROR, 6.65; ROR025, 6.1; χ2, 2,482.38; PRR, 6.41; EBGM, 5.69; EBGM05, 5.29), bone pain (n = 35; ROR, 13.78; ROR025, 9.4; χ2, 311.2; PRR, 13.75; EBGM, 10.59; EBGM05, 7.69), gait disturbance (n = 34; ROR, 2.82; ROR025, 1.99; χ2, 37.31; PRR, 2.88; EBGM, 2.7; EBGM05, 2.02), dental caries (n = 15; ROR, 23.16; ROR025, 12.32; χ2, 204.26; PRR, 23.14; EBGM, 15.23; EBGM05, 8.98), decrease in blood pressure (n = 15; ROR, 3.88; ROR025, 2.29; χ2, 29.35; PRR, 3.88; EBGM, 3.63; EBGM05, 2.33), and osteonecrosis (n = 9; ROR, 23.44; ROR025, 10.36; χ2, 123.67; PRR, 23.43; EBGM, 15.35; EBGM05, 7.75) were identified as AEs that were not previously outlined in the prescribing information of the medication. Our findings align with clinical observations, highlighting the emergence of previously unreported AE signals associated with MPA and their demographic and TTO characteristics. Further pharmaco-epidemiological studies are required to substantiate these observations.

Support of the luteal phase in programs for transferring thawed embryos into the uterine cavity in patients with overweight and obesity

Introduction. Progesterone levels are a critical factor for embryo implantation in in vitro fertilization (IVF) programs, including thawed embryo transfer programs. Overweight/obese patients often have lower blood progesterone concentrations in the luteal phase during IVF cycles, which requires an individual approach to planning luteal support in this category of patients.Aim. To compare the pregnancy ratе and miscarriage rates up to 12 weeks of pregnancy in overweight/obese patients who underwent a program of transfer of thawed embryos into the uterine cavity, depending on the type and route of administration of gestagens.Materials and methods. The study included 76 overweight or obese patients. All patients were treated for infertility using a program for transferring a thawed embryo into the uterine cavity; luteal phase support was carried out either using micronized progesterone, identical to natural, – the drug Utrogestan in a daily dose of 800 mg intravaginally (40 patients), or combination therapy was prescribed – vaginal gel with progesterone 90 mg in combination with the synthetic progestin dydrogesterone in a daily dose of 30 mg, taken orally (36 patients).Results. The rates of pregnancy and miscarriage in the first trimester were comparable in both groups and did not depend on differences in luteal support.Conclusions. The formation of the luteal phase of the cycle in patients with overweight/obesity is equally effective using various forms of gestagens. The use of micronized progesterone may be preferable in patients with overweight/obesity in terms of the ability to monitor blood progesterone levels, a more favorable metabolic profile when used vaginally, and the possibility of switching to oral administration of the drug in the event of the development of adverse local events.

Prolonged use of chlormadinone acetate and risk of intracranial meningioma: A population-based cohort study.

Chlormadinone acetate (CMA) is a synthetic progestin for which cases of intracranial meningioma have been reported following prolonged exposure. An observational cohort study was conducted based on the French national health data system. Women aged 10-70 years and who started CMA between 2007 and 2017 were included. Participants were considered to be exposed if they had received a cumulative dose >360 mg of CMA during the first 6 months and very slightly exposed (control group) when they had received a cumulative dose ≤360 mg. The outcome was surgery or radiotherapy for one or more intracranial meningioma(s). Poisson models assessed the relative risk (RR) of meningioma. In total, 828,499 women were included: 469,976 in the exposed group (mean age 39.1 years, SD 10.1) and 358,523 in the control group (38.3 years, SD 11.0). Surgery or radiotherapy for intracranial meningioma between 2007 and 2017 was recorded for 164 and 104 women in the exposed and control groups, respectively. The incidence of meningioma was 18.5 and 6.8 per 100,000 person-years for the exposed and control groups respectively (crude RR = 2.7, 95% confidence interval [CI] 2.1-3.5; age-adjusted RR = 3.1, 95% CI 2.4-4.0). Meningioma incidence reached almost 47 cases/100,000 person-years in the most exposed group (>8.64 g), giving an age-adjusted RR of 6.9, 95% CI 5.1-9.2, relative to the control group. A strong dose-effect relationship was observed between prolonged use of CMA and risk of meningiomas. As with other progestogens, meningiomas associated with CMA are more likely to be found at the base of the skull.

White matter integrity upon progesterone antagonism in individuals with premenstrual dysphoric disorder: A randomized placebo-controlled diffusion tensor imaging study

BackgroundPremenstrual dysphoric disorder (PMDD) is a depressive disorder triggered by fluctuations of progesterone and estradiol during the luteal phase of the menstrual cycle. Selective progesterone receptor modulation (SPRM), while exerting an antagonistic effect on progesterone and maintaining estradiol on moderate levels, has shown beneficial effects on the mental symptoms of PMDD. Progesterone is also known for its neuroprotective effects, while synthetic progestins have been suggested to promote myelination. However, the impact of SPRM treatment on white matter microstructure is unexplored. MethodsDiffusion tensor imaging was employed to collect data on white matter integrity in patients with PMDD, before and after treatment with ulipristal acetate (an SPRM) or placebo, as part of a double-blind randomized controlled-trial. Tract based spatial statistics were performed to investigate SPRM treatment vs. placebo longitudinal effects on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), on the whole white matter skeleton. ResultsVoxel-wise analyses indicated no change over time in any white matter microstructure metrics in individuals treated with SPRM versus placebo. Improvement in PMDD symptoms did not correlate with changes in white matter microstructure. In secondary, exploratory, cross-sectional comparisons during treatment, the SPRM group displayed lower FA and higher MD, RD, and AD than the placebo group in several tracts. ConclusionThe main findings suggest that SPRM treatment did not impact white matter microstructure compared with placebo. However, secondary exploratory analyses yielded between-group differences after treatment, which call for further investigation on the tracts potentially impacted by progesterone antagonism. Clinical trial registrationEUDRA-CT 2016–001719-19; “Selective progesterone receptor modulators for treatment of premenstrual dysphoric disorder. A randomized, double-blind, placebo-controlled study.”; https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE