Search Results (21)

Background: Oral progestogens, including megestrol acetate (MA) and medroxyprogesterone acetate (MPA), have largely been superseded by aromatase inhibitors, tamoxifen, and selective oestrogen receptor degraders (SERDs) in oestrogen receptor-positive (ER-positive) metastatic breast cancer. However, they remain an option as late-line therapy after failure of standard treatments. Contemporary data are limited, particularly in patients previously treated with CDK4/6 inhibitors. Methods: We conducted a multi-site retrospective analysis of patients with ER-positive metastatic breast cancer treated with MA or MPA between 2014 and 2024 at four hospital sites across London, United Kingdom. Patients were identified using pharmacy dispensing records. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and Cox regression. Subgroup analyses included prior CDK4/6 inhibitor exposure, histology and liver metastases. Results: A total of 116 patients were included. Median PFS was 2.4 months (95% CI 2.2–2.9), and median OS was 3.3 months (95% CI 2.7–4.9). Prior CDK4/6 inhibitor exposure was associated with shorter PFS (1.9 vs. 2.8 months; HR 1.59; 95% CI 1.08–2.35, p = 0.019) and a trend toward shorter OS (3.1 vs. 3.6 months; HR 1.18, 95% CI 0.80–1.75, p = 0.41). Similarly, liver metastases were associated with shorter PFS (2.3 vs. 2.8 months; HR 1.78, 95% CI 1.12–2.85, p = 0.015), with a trend toward worse OS (3.1 vs. 4.9 months; HR 1.45, 95% CI 0.93–2.25, p = 0.103). A subset of patients derived prolonged benefit, with a 6-month PFS rate of 16%. Toxicity was manageable; thromboembolic events and oedema occurred in 9% and 11% of patients respectively. Appetite improvement was reported in 10%. Conclusions: MA and MPA demonstrated modest but clinically relevant late-line activity in heavily pretreated, endocrine-refractory ER-positive metastatic breast cancer. While prior exposure to CDK4/6 inhibitors was associated with shorter PFS, patients without liver metastases appeared to derive the greatest benefit. These findings support a role for oral progestogens in selected patients who have exhausted standard therapeutic options. Full article

This study aims to synthesize contemporary evidence on the benefits, risks, and emerging options in menopausal hormone therapy (MHT), emphasizing the recent literature. A narrative review of peer-reviewed studies and guidelines (up to September 2025) from major databases (e.g., MEDLINE/PubMed, Embase, Cochrane) was conducted, with emphasis on the last five years and qualitative synthesis. MHT provides the most effective relief of vasomotor symptoms and is the first-line treatment for genitourinary syndrome of menopause, particularly with the use of low-dose local vaginal estrogen preparations; it also prevents early postmenopausal bone loss and reduces fractures in selected cases. Cardiovascular prevention is not an indication. Benefit–risk depends on timing, route, and dose. Initiation within 10 years of menopause as well as the use of transdermal estradiol at low–moderate doses are favored when cardiometabolic or thrombotic risk is salient. In contrast, oral regimens—particularly those using conjugated equine estrogens—are associated with higher risks of venous thromboembolism and stroke compared with transdermal 17 β-estradiol, and risk also varies by the type of progestogen used. Effects on breast cancer risks are regimen-specific: neutral to favorable with estrogen-alone after hysterectomy, but increasing with longer use of combined therapy. While the absolute risk of ovarian cancer remains small, evidence for colorectal cancer remains mixed. MHT confers modest improvements in sleep, mood, intercourse, and quality of life. Estetrol (E4) shows anti-VMS efficacy at the minimum effective oral dose and favorable pharmacology, but conclusive data on its long-term cardiovascular, thrombotic, and breast safety are pending. MHT should be individualized appropriately based on the patient, timing, route, dose, and choice of progestogen. The lowest effective dose should be used, alongside periodically reassessing the therapy as new evidence, including emerging data on E4, emerges. Full article

Endometrial cancer (EC) affects 3–14% of women under 40 who wish to preserve their fertility. The standard treatment for EC is a hysterectomy with salpingo-oophorectomy. However, for those desiring fertility preservation, oral progestogens such as medroxy-progesterone acetate (MPA) or megestrol acetate (MA) are the most common therapies in Fertility-Sparing Treatment (FST). Other treatments include gonadotropin-releasing hormone agonist (GnRHa), levonorgestrel-releasing intrauterine system (LNG-IUS), and metformin plus progestin. This comprehensive review evaluates the best FST options for women with reproductive potential. PubMed, EMBASE, and Scopus were searched in June 2023 using specific keywords. Studies included in the review focused on patients with EC undergoing FST, with outcomes such as complete response rate (CRR), recurrence rate (RR), pregnancy rate (PR), and live birth rate. Eighteen studies met the inclusion criteria, involving 23,976 patients. In only-oral progestin trials, CRR ranged from 18% to 100%; RR ranged from 0% to 81.8%; Death Rate ranged from 0% to 3.6%. In studies combining oral progestin with LNG-IUS, CRR ranged from 55% to 87.5%; RR ranged from 0% to 41.7%; Death Rate was 0%. Most patients with Stage IA EC received MPA or MA. Fertility-related outcomes were reported in 15 studies. PR ranged from 4 to 44 patients in trials involving only oral progestins. When combining oral progestin with LNG-IUS, PR ranged from 1 to 46 patients. Progestin therapy, including oral MPA and MA, is considered safe and effective, with limited evidence supporting the use of LNG-IUS. Full article

Background/Objective: The oral contraceptive pill (OCP) is widely used by women worldwide, yet the influence of the OCP on carbohydrate metabolism remains under-investigated, with existing studies being few and largely cross-sectional. The study objective was to assess, for the first time, the effect of the combined OCP on postprandial glycaemic response to an oral glucose bolus, using a randomised crossover design. Methods: The effect of a combined monophasic OCP phase on glucose homeostasis and metabolic profile was investigated in 21 healthy young women, who were regular users of either androgenic or anti-androgenic OCP formulations. Plasma glycaemic markers (glucose, insulin and C-peptide) were assessed prior to a 60 g glucose drink (fasting) and for a further 4 h postprandially; once during the “active” (hormone-containing) pill phase and once during the “inactive” (hormone-free) pill phase of the OCP usage cycle. Results: Despite no change in fasting values, in androgenic pill users, postprandial glucose and insulin responses to an oral glucose bolus were ~100% and ~50% greater, respectively, during the active versus inactive phase. In contrast, in anti-androgenic pill users there was no significant change in response between the two OCP usage cycle phases. Conclusions: These findings highlight an acute, but potentially detrimental, influence of the combined OCP on glucose homeostasis, particularly in users of formulations containing androgenic progestogens. Given the high global prevalence of OCP use and increasingly common prolonged active pill regimens, which may continue for months, years or even decades, potential cumulative effects of such changes on metabolic risk demand further investigation. Full article

Background: Breastfeeding is a process for not only nourishing infants but also for building a unique emotional bond between mother and child. Therefore, the ideal contraception during lactation should not affect lactation (milk composition, milk volume) and offspring development. Objectives: This study aims to analyze the literature on the safety of progestogen hormonal contraceptive methods during lactation. Methods: We conducted a thorough search across various databases, including the National Library of Medicine (PubMed), and the Cochrane Database, Drugs and Lactation Database (LactMed). Our search utilized specific phrases such as: “lactation” and “breastfeeding” and “oral contraception” with “drospirenone” or “desogestrel”, with “subcutaneous etonogestrel implant” or “etonogestrel implant”, with “levonorgestrel-releasing intrauterine system”, and “emergency contraception”, with “levonorgestrel” or “ulipristal acetate”. Conclusions: Based on published scientific reports, progestogen hormonal contraceptives can be considered a relatively safe solution for women desiring to continue feeding their infant with their milk while using hormonal contraception. It is important to seek guidance on selecting the best contraception method based on the latest medical knowledge, tailored to the individual needs and clinical circumstances of each woman and place of residence. A woman should always be informed of the potential risks of such a treatment and then allowed to make her own decision based on the knowledge received from a specialist. Full article

Uterine fibroids (leiomyomas and myomas) are the most common benign gynecological condition in patients presenting with abnormal uterine bleeding, pelvic masses causing pressure or pain, infertility and obstetric complications. Almost a third of women with fibroids need treatment due to symptoms. Objectives: In this review we present all currently available treatment modalities for uterine fibroids. Methods: An extensive search for the available data regarding surgical, medical and other treatment options for uterine fibroids was conducted. Review: Nowadays, treatment for fibroids is intended to control symptoms while preserving future fertility. The choice of treatment depends on the patient’s age and fertility and the number, size and location of the fibroids. Current management strategies mainly involve surgical interventions (hysterectomy and myomectomy hysteroscopy, laparoscopy or laparotomy). Other surgical and non-surgical minimally invasive techniques include interventions performed under radiologic or ultrasound guidance (uterine artery embolization and occlusion, myolysis, magnetic resonance-guided focused ultrasound surgery, radiofrequency ablation of fibroids and endometrial ablation). Medical treatment options for fibroids are still restricted and available medications (progestogens, combined oral contraceptives andgonadotropin-releasing hormone agonists and antagonists) are generally used for short-term treatment of fibroid-induced bleeding. Recently, it was shown that SPRMs could be administered intermittently long-term with good results on bleeding and fibroid size reduction. Novel medical treatments are still under investigation but with promising results. Conclusions: Treatment of fibroids must be individualized based on the presence and severity of symptoms and the patient’s desire for definitive treatment or fertility preservation. Full article

The genitourinary syndrome of menopause (GSM) is a widely occurring condition affecting millions of women worldwide. The current treatment of GSM involves the use of orally or vaginally administered estrogens, often with the risk of endometrial hyperplasia. The utilization of progestogens offers a means to counteract the effects of estrogen on the endometrial tissue, decreasing unwanted side effects and improving therapeutic outcomes. In this study, a norethindrone acetate (NETA)-loaded, hollow, cylindrical, and sustained release platform has been designed, fabricated, and optimized for implantation in the uterine cavity as a counter-estrogenic intervention in the treatment of GSM. The developed system, which comprises ethyl cellulose (EC) and polycaprolactone (PCL), has been statistically optimized using a two-factor, two-level factorial design, with the mechanical properties, degradation, swelling, and in vitro drug release of NETA from the device evaluated. The morphological characteristics of the platform were further investigated through scanning electron microscopy in addition to cytocompatibility studies using NIH/3T3 cells. Results from the statistical design highlighted the platform with the highest NETA load and the EC-to-PCL ratio that exhibited favorable release and weight loss profiles. The drug release data for the optimal formulation were best fitted with the Peppas–Sahlin model, implicating both diffusion and polymer relaxation in the release mechanism, with cell viability results noting that the prepared platform demonstrated favorable cytocompatibility. The significant findings of this study firmly establish the developed platform as a promising candidate for the sustained release of NETA within the uterine cavity. This functionality serves as a counter-estrogenic intervention in the treatment of GSM, with the platform holding potential for further advanced biomedical applications. Full article

Segesterone acetate (SA) or Nestorone, a fourth-generation progestogen, is a synthetic compound with high progestational activity and no androgenic, glucocorticoid, or anabolic effects. However, due to its oral inactivity, SA must be used by other routes, such as subcutaneous. Thus, considering its peculiar properties, the SA subdermal implant is successfully used in female contraception and postmenopausal hormone replacement therapy (HRT). In recent years, its potential uses in endometriosis, polycystic ovaries syndrome (PCOS), and a new therapeutic possibility for neuroprotection have made this treatment extremely interesting. However, the absence of a standardized dose and the long-term safety of SA implant therapy in women is still controversial. Here, we present the possible indications, doses, limitations, and side effects of SA implant therapy. Full article

Objective: to develop eligibility criteria for use in non-gynecological cancer patients. Methods: We searched all the articles published in peer-reviewed journals up to March 2021. We utilized the PICOS standards and the following selection criteria: menopausal women with a history of non-gynecological and non-breast cancer who underwent hormone replacement therapy (HRT) using various preparations (oestrogens alone or in combination with a progestogen, tibolone, or tissue selective oestrogen complex) and different routes of administration (including oral, transdermal, vaginal, or intra-nasal). We focused on randomized controlled trials as well as relevant extension studies or follow-up reports, specifically examining recurrence and mortality outcomes. Results: Women colorectal cancer survivors who use MHT have a lower risk of death from any cause than those survivors who do not use MHT. Women who are skin melanoma survivors using MHT have a longer survival rate than non-MHT survivors. There is no evidence that women lung cancer survivors who use MHT have a different survival rate than those who do not use MHT. Conclusions: MHT is safe for women who have a history of colorectal, lung, or skin melanoma cancers. Full article

Combined oral contraceptives (COC), are among the most widely used contraceptive methods in the world today. Despite the different changes in terms of estrogen/progestogen combinations and dosages, the thromboembolic risk for a woman who takes combined oral contraceptives persists to date. Methods: The review of relevant literature and international guidelines on prescription of combined oral contraceptives made it possible to create a proposal for informed consent to be used for prescribing. Results: The several sections of our consent proposal were designed according to a rationale in order to cover all the aspects presented by worldwide guidelines: how to take, adverse effects, advertisements, extra-contraceptive benefits and effects, a checklist for condition at risk of thromboembolism, the signature of the woman. Conclusions: An informed consent to standardize combined oral contraceptives prescription can improve women’s eligibility, mitigate thromboembolic risk, and assure legal protection to healthcare providers. In this systematic review in particular, we refer to the Italian medical–legal scenario, to which our group of researchers belongs. However, the model proposed was designed in the respect of main healthcare organization guidelines, and it could be easily used by any center in the world. Full article

Recent studies suggest estradiol (E₂)/natural progesterone (P) confers less breast cancer risk compared with conjugated equine estrogens (CEE)/synthetic progestogens. We investigate if differences in the regulation of breast cancer-related gene expression could provide some explanation. This study is a subset of a monocentric, 2-way, open observer-blinded, phase 4 randomized controlled trial on healthy postmenopausal women with climacteric symptoms (ClinicalTrials.gov; EUCTR-2005/001016-51). Study medication was two 28-day cycles of sequential hormone treatment with oral 0.625 mg CEE and 5 mg of oral medroxyprogesterone acetate (MPA) or 1.5 mg E₂ as percutaneous gel/day with the addition of 200 mg oral micronized P. MPA and P were added days 15–28/cycle. Material from two core-needle breast biopsies in 15 women in each group was subject to quantitative PCR (Q-PCR). The primary endpoint was a change in breast carcinoma development gene expression. In the first eight consecutive women, RNA was extracted at baseline and after two months of treatment and subjected to microarray for 28856 genes and Ingenuity Pathways Analysis (IPA) to identify risk factor genes. Microarray analysis showed 3272 genes regulated with a fold-change of >±1.4. IPA showed 225 genes belonging to mammary-tumor development function: 198 for CEE/MPA vs. 34 for E₂/P. Sixteen genes involved in mammary tumor inclination were subject to Q-PCR, inclining the CEE/MPA group towards an increased risk for breast carcinoma compared to the E₂/P group at a very high significance level (p = 3.1 × 10⁻⁸, z-score 1.94). The combination of E₂/P affected breast cancer-related genes much less than CEE/MPA. Full article

Hormonal contraception (HC) can influence the migraine burden and should be considered in the comprehensive management of women with migraine. In this study, we aim to investigate the influence of migraine and migraine aura on the prescribing behavior of combined oral contraception (COC) and progestogen monotherapy (PM) in gynecological outpatient care. From October 2021 to March 2022, we performed an observational, cross-sectional study using a self-administered online-based survey. The questionnaire was distributed by mail and e-mail among 11,834 practicing gynecologists in Germany using the publicly available contact information. A total of 851 gynecologists responded to the questionnaire, of whom 12% never prescribe COC in the presence of migraine. Further 75% prescribe COC depending on the presence of limiting factors such as cardiovascular risk factors and comorbidities. When deciding to start PM, migraine appears to be less relevant, as 82% prescribe PM without restrictions. In the presence of aura, 90% of gynecologists do not prescribe COC at all, while PM is prescribed in 53% without restrictions. Almost all gynecologists reported to be actively involved in migraine therapy by having already initiated (80%), discontinued (96%), or changed (99%) HC due to migraine. Our results reveal that participating gynecologists actively consider migraine and migraine aura before and while prescribing HC. Gynecologists appear cautious in prescribing HC in patients with migraine aura. Full article

Progesterone is well known for its numerous endocrinologic roles in pregnancy but is also endowed with fascinating immunomodulatory capabilities. It can downregulate the induction of inflammatory reactions, the activation of immune cells and the production of cytokines, which are critical mediators of immune responses. These features appear to be critical to the success of pregnancy, given the ability of maternal immune reactivity to interfere with pregnancy and to contribute to several pregnancy complications. This review summarizes the contribution of maternal immune effectors in general, and cytokines in particular, to pregnancy complications such as recurrent miscarriage, pre-eclampsia and preterm labor; it describes the promise offered by supplementation with progesterone and the oral progestogen dydrogesterone, as well as the progesterone-induced blocking factor in the prevention and/or treatment of these serious complications. Full article

To evaluate the effectiveness of a new class of medical drugs, namely oral gonadotropin-releasing hormone (GnRH) antagonists, in the management of premenopausal women with endometriosis-associated pelvic pain. We reviewed the most relevant papers (n = 27) on the efficacy of new medical alternatives (oral GnRH antagonists) as therapy for endometriosis. We first briefly summarized the concept of progesterone resistance and established that oral contraceptives and progestogens work well in two-thirds of women suffering from endometriosis. Since clinical evidence shows that estrogens play a critical role in the pathogenesis of the disease, lowering their levels with oral GnRH antagonists may well prove effective, especially in women who fail to respond to progestogens. There is a need for reliable long-term oral treatment capable of managing endometriosis symptoms, taking into consideration both the main symptoms and phenotype of the disease. Published studies reviewed and discussed here confirm the efficacy of GnRH antagonists. There is a place for GnRH antagonists in the management of symptomatic endometriosis. Novel algorithms that take into account the different phenotypes are proposed. Full article

Progestogens are frequently administered during early pregnancy to patients undergoing assisted reproductive techniques (ART) to overcome progesterone deficits following ART procedures. Orally administered dydrogesterone (DG) shows equal efficacy to other progestogens with a higher level of patient compliance. However, potential harmful effects of DG on critical pregnancy processes and on the health of the progeny are not yet completely ruled out. We treated pregnant mice with DG in the mode, duration, and doses comparable to ART patients. Subsequently, we studied DG effects on embryo implantation, placental and fetal growth, fetal-maternal circulation, fetal survival, and the uterine immune status. After birth of in utero DG-exposed progeny, we assessed their sex ratios, weight gain, and reproductive performance. Early-pregnancy DG administration did not interfere with placental and fetal development, fetal-maternal circulation, or fetal survival, and provoked only minor changes in the uterine immune compartment. DG-exposed offspring grew normally, were fertile, and showed no reproductive abnormalities with the exception of an altered spermiogram in male progeny. Notably, DG shifted the sex ratio in favor of female progeny. Even though our data may be reassuring for the use of DG in ART patients, the detrimental effects on spermatogenesis in mice warrants further investigations and may be a reason for caution for routine DG supplementation in early pregnancy. Full article