Search Results (51)

Male hormonal contraception has been the focus of extensive research efforts aimed at identifying effective and reversible methods for male fertility control. This review summarizes the current state of knowledge, key achievements, and future directions in the development of male hormonal contraception. A review was conducted using the PubMed, Embase, and Scopus databases. The search strategy included terms such as “male hormonal contraception”, “Nestorone”, “7α,11β-Dimethyl-19-nortestosterone 17β-undecanoate (DMAU)” and “11β-methyl-19-nortestosterone 17β-dodecylcarbonate (11β-MNTDC)”. A total of 107 references were analyzed to synthesize the most relevant findings regarding the hormonal contraceptive agents under investigation. The review outlines historical and recent advancements in male hormonal contraception, highlighting compounds that have demonstrated limitations in effectiveness, side effects, or inconvenient administration. Notable candidates under study include 7α-methyl-19-nortestosterone (MENT), DMAU, 11β-MNTDC, and the combination of segesterone acetate with testosterone in gel form. These agents show promise due to their ability to suppress follicle-stimulating hormone (FSH) and luteinizing hormone (LH), leading to effective spermatogenesis inhibition with minimal side effects. Additionally, the phenomenon of spermatogenic rebound is considered. Among the investigated agents, oral DMAU, 11β-MNTDC, and the Nestorone–testosterone gel appear to be the most promising candidates for male hormonal contraception due to their high efficacy, user-friendly administration, and favorable safety profiles. However, further large-scale clinical trials are necessary to confirm their long-term effects on human health and fertility, ensuring their viability as future contraceptive options. Full article

Background/Objectives: Migraines are a common neurological disorder that significantly impact women, especially during their reproductive years. Hormonal, neurological, and lifestyle factors shape migraine patterns, with fluctuations during menstruation, pregnancy, perimenopause, and menopause influencing migraine prevalence and severity. This expert opinion explores current challenges, therapeutic strategies, and future directions for personalized care, addressing the limited inclusion of women in clinical research across different life stages. Methods: In order to focus on hormonal influences, pharmacological and non-pharmacological therapies, including CGRP monoclonal antibodies, neuromodulation, and lifestyle interventions, a comprehensive analysis of literature, in particular on clinical trials, real-world studies, and guidelines on migraine management was performed. Emerging digital tools and AI-based approaches were also evaluated to improve personalized care for women with migraine. Results: Hormonal therapies, including contraceptives and HRTs, present both risks and benefits, particularly for women with migraines with aura, highlighting the need for individualized approaches. Advances in CGRP-targeted therapies have shown effectiveness in preventing refractory migraines. Non-pharmacological treatments, such as neuromodulation, acupuncture, and lifestyle adjustments, further expand the treatment landscape. However, research gaps remain, particularly regarding hormonal influences on migraines during pregnancy and menopause. Conclusions: Future research should prioritize female-specific clinical trials to better understand the impact of hormonal changes on migraines. Tailored therapies combining pharmacological, non-pharmacological, and digital solutions are essential for improving care. A multidisciplinary approach integrating personalized medicine, technological advancements, and patient education is crucial to optimizing outcomes and enhancing quality of life for women with migraine. Full article

Background/Objectives: This study aims to assess the effects of combined hormonal contraceptives (CHCs) on bone metabolism markers. It primarily measures osteocalcin and additionally examines other bone health markers, seeking to determine their responses to estrogen–progestogen treatments. Methods: This study involved a comprehensive evaluation of the pertinent literature and a meta-analysis explicitly conducted on data describing women of reproductive age. The analysis encompassed accessible papers ranging to December 2024 (i.e., those listed in PubMed/Medline, Embase, Scopus, the Cochrane Database, International Clinical Trials Registry, and ClinicalTrials.gov). We examined published randomized controlled trials (RCTs) and prospective studies. The quality of the studies was assessed using the Cochrane tool for RCTs and the Newcastle–Ottawa Scale for prospective studies. The selected indicators for primary and secondary outcomes were ascertained by standardized mean change (SMC), displaying the difference between conditions before and after treatment. Trends were evaluated using meta-regressions. Results: Ultimately, 34 articles out of 1924 identified items met the inclusion criteria, covering 33 unique studies. In EE/E4 combinations, osteocalcin dropped significantly (SMC −0.54 (CI.95 −0.64/−0.43) and −0.43 (CI.95 −0.76/−0.10)). Similar effects were observed for other bone-formation and reabsorption markers, with less significant reductions observed in E2-containing CHC (e.g., alkaline phosphatase (bone) EE combinations, SMC −0.39 (CI.95 −0.67/−0.11); P1NP E2 combination, 0.12 (CI.95 −0.10/0.33); and EE combinations, −0.55 (CI.95 −0.83/−0.26)). The reduction patterns also exhibited differences according to the women’s age (e.g., osteocalcin in EE combinations ≤21, SMC −0.63 (CI.95 −0.77/−0.49) and >21, SMC −0.42 (CI.95 −0.61/−0.24); alkaline phosphatase (bone) EE combinations ≤21, SMC −0.55 (CI.95 −0.86/−0.24) and >21, SMC −0.06 (CI.95 −0.47/0.35)). This analysis found that CHC maintains or reduces bone turnover in childbearing women, with effects varying by age and hormone combination. Moreover, bone-formation and reabsorption markers correlated positively to pro-androgenic progestins (p < 0.05). Thus, estrogen–progestogen combinations reduce bone turnover less when weak estrogens and a pro-androgenic or neutral progestin are present. Conclusions: This study found that CHCs reduce bone turnover, with natural estrogens and androgenic progestins appearing to be more beneficial than EE and anti-androgenic types. These findings would potentially influence decisions relevant to CHC prescriptions during a woman’s reproductive phases, emphasizing the need for additional research to tailor CHC usage to bone health. Full article

Background/Objectives: Achilles and hamstring tendinopathies are common injuries in runners, and extracorporeal shockwave therapy (ESWT) may be an effective treatment. Runners are at risk for lower extremity tendinopathies and the Male and Female Athlete Triad (Triad). The purpose of this study is to evaluate the association of sex, exposure to hormonal contraceptives, menopause, and Triad-related risk factors with ESWT outcomes in the treatment of Achilles and hamstring tendinopathy. Methods: This is a retrospective cohort study of runners with either Achilles or hamstring tendinopathy who received radial or combined radial and focused ESWT. Tendon function was measured using Victorian Institute of Sport Assessment (VISA) questionnaires completed before and following treatment. Treatment success was defined by a change in VISA score that met the minimal clinically important difference (MCID). Results: There were 88 runners (54.5% female, 45.5% male) with Achilles (52.3%) or hamstring (47.7%) tendinopathy. No measurable difference was found in the proportion of females and males overall that achieved the MCID (57.1% and 72.5%, p = 0.17). Similar rates of females and males met MCID for Achilles (77.8% and 75.0%, p = 0.83) and hamstring tendinopathy (46.7% and 66.7%, p = 0.24). However, females with Achilles or hamstring tendinopathy who used oral contraceptive pills (OCPs) were less likely to meet the MCID compared to females not on OCPs (p = 0.031); this finding was present in a subgroup analysis of runners with only Achilles tendinopathy (p = 0.025). No associations were found between achieving the MCID and Triad risk factors, including body mass index, energy availability, weight-related behaviors, bone health, or menstrual function (all p > 0.05). Conclusions: Female and male runners reported similar success rates for ESWT, and Triad risk factors were not found to impact outcomes. However, females who used oral contraceptive pills were less likely to achieve the MCID from ESWT. Full article

Background: Abnormal uterine bleeding (AUB) is a common gynecological complaint affecting women of reproductive age. This study aimed to explore the management of AUB using the FIGO PALM-COEIN classification system. Methods: A cross-sectional study was conducted at King Abdullah bin Abdulaziz University Hospital, reviewing 500 medical records of women aged 20–50 years with AUB. Data on demographics, clinical characteristics, PALM-COEIN classification, and treatment modalities were collected and analyzed. Results: The majority of participants were aged 20–29 years (43%) and overweight or obese (64.2%). Ovulatory dysfunction (31.6%) was the most common identifiable cause of AUB, followed by leiomyoma (16.8%). Hormonal treatments, particularly combined oral contraceptive pills, were associated with improved outcomes (OR = 2.15, p < 0.001) and reduced anemia prevalence (p = 0.042). Age (OR = 0.95, p = 0.015) and BMI (OR = 1.10, p = 0.005) were significant predictors of treatment response. The presence of leiomyoma decreased the odds of treatment success (OR = 0.55, p = 0.007), while ovulatory dysfunction increased the likelihood of response (OR = 1.75, p = 0.003). Conclusions: The study highlights the complex nature of AUB and the effectiveness of hormonal treatments in its management. Findings emphasize the need for individualized treatment approaches based on the underlying etiology and patient characteristics. Future research should focus on long-term outcomes and optimizing management strategies for complex cases. Full article

Background/Objectives: Endometriosis is a chronic condition that affects 6–10% of women of reproductive age, with pain and infertility being its primary symptoms. The most common aspects of pain are overall pelvic pain, dysmenorrhea, and dyspareunia. Our aim was to compare the available medical treatments for endometriosis-related pain. Methods: A systematic search was conducted in three medical databases to assess available drug options for pain management. Randomized controlled trials (RCTs) investigating various medical treatments for endometriosis-related pain on different pain scales were included. Results were presented as p-scores and, in cases of placebo controls, as mean differences (MD) with 95% confidence intervals (CI). From the available data, a network meta-analysis was carried out. Results: The search yielded 1314 records, of which 45 were eligible for data extraction. Eight networks were created, and a total of 16 treatments were analyzed. The highest p-score, meaning greatest pain relief (p-score: 0.618), for the treatment of dysmenorrhea was achieved using gonadotropin-releasing hormone (GnRH) agonists for 3 months on a scale of 0–100. Additionally, a p-score of 0.649 was attained following a 6-month treatment with GnRH agonists combined with hormonal contraceptives (CHCs). In the case of dyspareunia on a scale of 0–100 following 3 months of treatment, CHCs (p-score: 0.805) were the most effective, and CHCs combined with aromatase inhibitors (p-score: 0.677) were the best treatment option following 6 months of treatment. In the case of overall pelvic pain, CHCs (p-score: 0.751) yielded the highest p-score on a scale of 0–100 following 3 months of treatment, and progestins combined with aromatase inhibitors (p-score: 0.873) following 6 months of treatment. Progestins (p-score: 0.901) were most effective in cases of overall pelvic pain on a scale of 0–3 following 3 months of treatment. Conclusions: Our network meta-analysis showed that in cases of dysmenorrhea, GnRH agonists supplemented with CHCs reduced pain the most following 3 months of treatment. Regarding dyspareunia CHCs were most effective, and in the case of overall pelvic pain, CHCs or progestins combined with aromatase inhibitors yielded the most desirable results. Full article

Introduction: Currently, progesterone is notably absent from conventional feminizing hormone therapies for transgender women. Anecdotal reports indicate the potential for health advantages following the incorporation of progesterone into treatment regimens. The primarily female hormone, progesterone naturally surges in women during the menstrual luteal phase. When administered exogenously, it may expedite bodily changes that are pivotal for gender transition. Progesterone holds promise as a potential remedy for various health conditions prevalent in the transgender woman population. Methods: This narrative review synthesizes existing literature and presents a comprehensive account of the administration of exogenous progesterone in transgender women. A literature search was conducted using the PubMed, Embase, ScienceDirect, and ResearchGate databases. The following keywords were used in the search: progesterone, transgender, breast neoplasms, lactation, prostate, testicular neoplasms, and thrombosis. These terms were combined using Boolean operators. The results of the initial search were screened by three independent reviewers based on their relevance to the topic under study. Results: A total of 104 studies were initially identified as meeting the criteria for inclusion. Following an assessment based on the contents of the title, abstract, and full text, 39 studies were deemed eligible for inclusion. A critical examination of health outcomes was conducted across key sections, including breast development, mental health, lactation, cancer risk (breast and prostate), thrombosis, and nervous and other systems. Discussion: The use of progesterone in the transgender woman population is a topic that has yet to be sufficiently researched. The limited sample size, short follow-up periods, and lack of randomization restrict the potential for achieving a robust scientific evidence base. In order to gain a fuller understanding of this topic, findings from studies on contraception, hormone replacement therapy, and animal models were considered. Conclusions: Progesterone may have a beneficial effect on the bodies of transgender women without significant adverse health effects. Further investigation through well-designed studies is recommended. Randomized controlled trials that include various dosages, broad and long-term effects, and precise demographics are needed. There is an immediate need for more knowledge to create appropriate patent and clinical practice guidelines. Full article

Background/Objectives: Endometriosis is characterized by the presence of ectopic endometrial-like glands and stroma outside the endometrial cavity, which mainly occurs in the pelvic cavity. Pulmonary endometriosis, or thoracic endometriosis syndrome (TES), describes the rare presence of endometrial-like cells in the thoracic cavity and includes catamenial pneumothorax, catamenial hemothorax, hemoptysis, and lung nodules. Our aim is to summarize the results of all reported cases of TES. Methods: Extensive research was conducted through MEDLINE/PUBMED using the keywords “thoracic endometriosis”, “thoracic endometriosis syndrome”, “catamenial pneumothorax”, “catamenial hemoptysis”, and “TES”. Following PRISMA guidelines, all published cases of TES between January 1950 and March 2024 were included. A systematic review of 202 studies in English, including 592 patients, was performed. Results: The median age of women with TES is 33.8 years old. The most common clinical presentation is catamenial pneumothorax (68.4%), while lesions are mainly found in the right lung unilaterally (79.9%). Chest computed tomography (CT) was used alone or after an X-ray to determine the pathological findings. Ground-glass opacity nodules and cystic lesions represent the most common finding in CT, while pneumothorax is the most common finding in X-rays. Video-assisted thoracoscopic surgery (VATS) is the main therapeutic approach, usually in combination with hormonal therapy, including GnRH analogues, progestins, androgens, or combined oral contraceptives. Hormonal therapy was also administered as monotherapy. Symptom recurrence was reported in 10.1% of all cases after the treatment. Conclusions: High clinical awareness and a multidisciplinary approach are necessary for the best clinical outcome for TES patients. More studies are required to extract safer conclusions. 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

Polycystic Ovary Syndrome (PCOS) is a complex hormonal disorder that is associated with heightened metabolic risks. While oxidative stress (OS) is known to play a role in PCOS, the precise nature of the relationship between PCOS and increased OS remains not entirely understood. Combined oral contraceptives (COCs) are the first-line treatment to regulate menstrual cycles and androgen levels, but their impact on oxidative stress requires further study. We conducted a transcriptomic analysis using RNAseq and assessed the levels of various oxidative stress (OS) markers in serum samples from women with PCOS and controls and whether they were using combined oral contraceptives (COCs), including enzymatic activities, FRAP, and 8-isoprostane (8-iso). A total of 359 genes were differentially expressed in women with PCOS compared to control women. Genes differentially expressed were enriched in functions related to inflammation and, interestingly, oxidative stress response. In controls, 8-iso levels were increased in women using COCs, whereas in women with PCOS, 8-iso levels were reduced in those using oral contraceptives (191.1 ± 97 vs. 26.4 ± 21 pg/mL, p: <0.0001). Correlation analyses showed a trend for a negative correlation between 8-iso and Ferriman score in women with PCOS consuming COCs (r = −0.86, p = 0.06) and a negative correlation between GSH and hyperandrogenism in women with PCOS (r = −0.89, p = 0.01). These results reveal the presence of lipid peroxidation in women with PCOS, which was modified by the use of COCs, providing new insights into the pathophysiology of PCOS in the Chilean population. Full article

Background: Levonorgestrel implant is a highly effective hormonal contraceptive, but its efficacy may be compromised when used with cytochrome enzyme inducers such as efavirenz. The primary aim of this study was to evaluate methods of mitigating the drug interaction. Methods: Using a physiologically-based pharmacokinetic (PBPK) model for levonorgestrel that we developed within the Simcyp^® program, we evaluated a higher dose of levonorgestrel implant, a lower dose of efavirenz, and the combination of both, as possible methods to mitigate the interaction. In addition, we investigated the impact on levonorgestrel total and unbound concentrations of other events likely to be associated with efavirenz coadministration: changes in plasma protein binding of levonorgestrel (as with displacement) and high variability of efavirenz exposure (as with genetic polymorphism of its metabolism). The range of fraction unbound tested was 0.6% to 2.6%, and the range of efavirenz exposure ranged from the equivalent of 200 mg to 4800 mg doses. Results: Levonorgestrel plasma concentrations at any given time with a standard 150 mg implant dose are predicted to be approximately 68% of those of control when given with efavirenz 600 mg and 72% of control with efavirenz 400 mg. With double-dose levonorgestrel, the predictions are 136% and 145% of control, respectively. A decrease in levonorgestrel plasma protein binding is predicted to primarily decrease total levonorgestrel plasma concentrations, whereas higher efavirenz exposure is predicted to decrease total and unbound concentrations. Conclusions: Simulations suggest that doubling the dose of levonorgestrel, particularly in combination with 400 mg daily efavirenz, may mitigate the drug interaction. Changes in levonorgestrel plasma protein binding and efavirenz genetic polymorphism may help explain differences between model predictions and clinical data but need to be studied further. Full article

Intravaginal rings (IVRs) represent a well-established, woman-controlled and sustained vaginal drug delivery system suitable for a wide range of applications. Here, we sought to investigate the differences in etonogestrel (ENG) and ethinyl estradiol (EE) release from a 3D-printed IVR utilizing continuous liquid interface production (CLIP™) (referred to as CLIP_LOW for low drug loading and CLIP_HIGH IVRs for high drug loading) and NuvaRing, a commercially available injection molded IVR. We conducted in vitro release studies in simulated vaginal fluid to compare the release of ENG and EE from CLIP_LOW IVRs and NuvaRing. CLIP_LOW IVRs had a similar hormone dose to NuvaRing and exhibited slightly slower ENG release and greater EE release in vitro compared to NuvaRing. When administered to female sheep, NuvaRing demonstrated greater ENG/EE levels in plasma, vaginal tissue and vaginal fluids compared to CLIP_LOW IVR despite similar drug loadings. Leveraging observed hormones levels in sheep from NuvaRing as an effective contraceptive benchmark, we developed a long-acting CLIP_HIGH IVR with increased ENG and EE doses that demonstrated systemic and local hormone levels greater than the NuvaRing for 90 days in sheep. No signs of toxicity were noted regarding general health, colposcopy, or histological analysis in sheep after CLIP_HIGH IVR administration. Our results provided (1) a comparison of ENG and EE release between a 3D-printed IVR and NuvaRing in vitro and in vivo, (2) a preclinical pharmacokinetic benchmark for vaginally delivered ENG and EE and (3) the generation of a 90-day CLIP IVR that will be utilized in future work to support the development of a long-acting ENG/EE IVR combined with an antiretroviral for the prevention of HIV and unplanned pregnancy. Full article

In this narrative review, we attempt to provide an overview of the evidence regarding the role of estrogen (receptors) in cutaneous melanoma (CM). We reviewed 68 studies and 4 systematic reviews and meta-analyses published from 2002 up to and including 2022. The prevailing presence of estrogen receptor β (ERβ) instead of estrogen receptor α (ERα) in CM is notable, with ERβ potentially playing a protective role and being less frequently detected in progressive cases. While men with CM generally experience a less favorable prognosis, this distinction may become negligible with advancing age. The role of oral contraceptives (OC) and hormone replacement therapy (HRT) in CM remains controversial. However, recent studies tend to associate the use of these exogenous hormones with a heightened risk of CM, mostly only when using estrogen therapy and not in combination with progesterone. On the contrary, the majority of studies find no substantial influence of in vitro fertilization (IVF) treatment on CM risk. Reproductive factors, including younger age at first childbirth, higher parity, and shorter reproductive life, show conflicting evidence, with some studies suggesting a lower CM risk. We suggest an important role for estrogens in CM. More research is needed, but the integration of estrogens and targeting the estrogen receptors in melanoma therapy holds promise for future developments in the field. 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 synthetic hormone 17α ethinyl estradiol (EE2) is a molecule widely used in female contraceptives and recognized as a contaminant of attention (Watch List) in the European Union due to its high consumption, endocrine effects and occurrence in aquatic environments. Its main source of introduction is domestic sewage where it can be associated with other contaminants such as microplastics (MPs). Due to their characteristics, they can combine with each other and exacerbate their isolated effects on biota. This study evaluated the combined effects of microplastics (MPs) and 17α ethinylestradiol (EE2) on two tropical estuarine invertebrate species: Crassostrea gasar and Ucides cordatus. Polyethylene particles were spiked with EE2 and organisms were exposed to three treatments, categorized into three groups: control group (C), virgin microplastics (MPs), and spiked microplastics with EE2 (MPEs). All treatments were evaluated after 3 and 7 days of exposure. Oysters exhibited changes in phase 2 enzymes and the antioxidant system, oxidative stress in the gills, and reduced lysosomal membrane stability after exposure to MPs and MPEs. Crabs exposed to MPs and MPEs after seven days showed changes in phase 1 enzymes in the gills and changes in phases 1 and 2 enzymes in the hepatopancreas, such as disturbed cellular health. The combined effects of microplastics and EE2 increased the toxicity experienced by organisms, which may trigger effects at higher levels of biological organization, leading to ecological disturbances in tropical coastal ecosystems. Full article