Search Results (82)

Understanding hormone patterns in free-ranging African elephants can provide critical insights for the management of elephants in human care, particularly in addressing reproductive anomalies and the rising prevalence of obesity in zoo populations. This study is the first to establish baseline values for glucose, insulin, and leptin, and their potential relationships with reproductive and stress hormones. We measured the hormones in serum samples collected opportunistically in Kruger National Park between 2000 and 2016. Endocrine profiles were compared across age groups in both male and female elephants and between the wet and dry seasons. In females, progestogen and prolactin levels were highest in adults, and were not significantly correlated with the glucose-to-insulin (G/I) ratio or leptin. In males, testosterone levels were higher in adults, and the G/I ratio was a significant predictor of testosterone concentrations. Seasonal variations revealed that, in males, testosterone levels were higher, and cortisol concentrations were lower during the rainy season. In females, cortisol concentrations were negatively associated with progestogen levels during the dry season. These benchmarks offer zoos a reference point to assess whether current management approaches are effective, and how natural variation with the season may impact hormone levels. Full article

Background: Gestrinone is a synthetic hormone derived from 19-nortestosterone, exhibiting androgenic, anabolic, anti-progestogenic, and antiestrogenic effects. Gestrinone subcutaneous implants have been used “off label” for aesthetic purposes due to their anabolic action, promoting accelerated metabolism and muscle gain. Objective: Our goal is to conduct a systematic review focused exclusively on identifying the safety profile of gestrinone use, without addressing efficacy. Methods: This systematic review was performed according to the Joanna Briggs Institute and Cochrane Collaboration recommendations and is reported following the Preferred Reporting Items for Systematic Reviews and Network Meta-Analyses. This article’s searches were carried out in the PubMed, Embase, and Web of Science databases. Results: A total of 32 articles were included in this study. The reported adverse events associated with the use of gestrinone were amenorrhea (41.4% of cases), acne, seborrhea (42.7% of reports), decreased libido (26.5%), and hot flushes (24.2%). Other nonspecific symptoms such as hoarseness and cramps were also fairly reported (3.5% and 18.6%, respectively). Other reported effects were associated with breast size reduction (23.7% of patients) and increased transaminases (15.1%). Most studies (40%, n = 24 studies) found significant weight gain (ranging from 0.9 to 8 kg per patient). Abnormalities in bone mineral density were reported in four studies. Conclusions: The evidence remains insufficient to fully understand the risks of gestrinone uses associated with its widespread, unregulated use. Thus, further standardized studies and regulatory oversight to ensure patient safety are needed to mitigate potential health risks. Full article

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. 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

Progestogens’ anti-anxiety and anti-depressive effects and mechanisms are not well-understood. Progestogens are hypothesized to have anti-anxiety and anti-depressive effects on behavior, independent of actions at nuclear progestin receptors (NPRs) and dependent on allopregnanolone (5α-pregnan-3α-ol-20-one; 3α,5α-THP), a 5α-reduced, neuroactive metabolite of progesterone (P₄). Adult c57 mice in behavioral estrus (proestrus; pro) showed more anti-anxiety-like and anti-depressant-like behavior and higher levels of estradiol (E₂), P₄, and allopregnanolone in the hippocampus/amygdala complex. Proestrus c57 > 5α-reductase knockout (5αRKO) mice made more central entries in an open field than diestrus c57 and 5αRKO mice that were not different. Ovariectomized (OVX) c57 mice administered 1, 2, or 4 mg/kg P₄ SC showed dosage-dependent increases in central entries in an open field (more anti-anxiety-like behavior); 5αRKO mice had maximal increases at 1–2 mg/kg P₄. OVX c57 and 5αRKO mice showed maximum increases in central entries with SC 3α,5α-THP (4 mg/kg), and c57s showed a similar maximal response to P₄ (4 mg/kg), but 5αRKOs response was half at that dosage. P₄ (4 mg/kg SC to OVX c57 or progestin receptor knockout (PRKO) mice decreased immobility (depression-like behavior) in the forced swim task. Effects of E₂ and veh were similar in both groups. Levels of 3α,5α-THP in the hippocampus/amygdala were consistent with effects on central entries in the open field. Levels of brain-derived neurotrophic factor (BDNF) in the hippocampus/amygdala were greater among E₂-primed (0.09 mg/kg, SC) vs vehicle-administered mice. In sum, adult female mice can be responsive to P₄ for anti-anxiety/anti-depressant-like behavior; such effects may be independent of NPRs but require 5α-reduction and E₂’s priming actions at BDNF in the hippocampus/amygdala complex. Full article

Endometriosis afflicts 10% of women in their reproductive years and nearly half of women with infertility, and its etiology is not yet clear. Pharmacological therapy is generally based on progestins like progestogen. This drug binds to progesterone receptors with many known side effects. Here, we describe the case of a 33-year-old woman surgically treated for endometriosis who continued with drug therapy based on estradiol valerate and dienogest. Approximately 21 months after treatment, she reported ocular symptoms with vision alteration, diplopia, and metamorphopsia related to central serous chorioretinopathy (CSC). After the discontinuation of combined progestin-based treatment, the CSC fully subsided. Semeiological, clinical, and laboratory approaches were adopted, and urinary steroids were measured. A slight increase in prolactinemia in the absence of macro-prolactinemia was reported. The steroidal profile appeared without abnormalities, although a slight alteration of estrogen balance was noted. Considering the pharmacodynamics of dienogest versus selective progesterone receptor modulators, it can be assumed that patients’ clinical events are related to specific site response to steroids that bind the progesterone receptor. Dienogest may have induced the CSC as a not yet characterized side effect of the drug. Undoubtedly, further specific studies are needed concerning the metabolic and pharmacodynamic aspects that cannot be exhaustively covered here. Full article

Introduction and importance: Extrapelvic endometriosis, confined exclusively to the body of the rectus abdominis muscle, is a rare form of abdominal wall endometriosis. While its etiopathology remains unclear, it is often diagnosed in healthy women who present with atypical symptoms and localization unrelated to any incision site, or in the absence of a history of endometriosis or previous surgery. Presentation of the case: Here, we describe a unique case of intramuscular endometriosis of the rectus abdominis muscle in a healthy 39-year-old Caucasian woman. The condition was located away from any prior incisional scars and presented without typical symptoms or concurrent pelvic disease, making diagnostic imaging unclear. After partial surgical resection of the endometriotic foci, the diagnosis was confirmed histologically. Progestogen-based supportive medication was initiated to prevent the need for additional surgeries and to reduce the risk of recurrence. After 6 years of follow-up and continued progestogen treatment, the patient remains symptom-free and has shown no recurrence of the disease. Clinical discussion: Endometriosis of the rectus abdominis muscle exhibits specific characteristics in terms of localization, etiopathology, symptomatology, and diagnostic imaging, suggesting that it should be considered a distinct clinical entity. Conclusions: Although rare, primary endometriosis of the rectus abdominis muscle should be included in the differential diagnosis for women of childbearing age. Early diagnosis is essential to avoid delayed recognition, tissue damage, and to minimize the risk of recurrence or malignant transformation. Given the increasing frequency of gynecologic and laparoscopic surgeries worldwide, it is crucial to establish standardized reporting protocols, follow-up timelines, and imaging assessments during specific phases of the menstrual cycle. Standardization will help raise awareness of this disease, and further our understanding of its pathogenesis, risk factors, recurrence patterns, and potential for malignant transformation—factors that are still not fully understood. 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/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

Gonadal steroids exert different effects on the central nervous system (CNS), such as preserving neuronal function and promoting neuronal survival. Estradiol, progesterone, and testosterone reduce neuronal loss in the CNS in animal models of neurodegeneration. However, hormone replacement therapy has been associated with higher rates of endometrial, prostate, and breast cancer. Tibolone (TIB), the metabolites of which show estrogenic and progestogenic effects, is an alternative to reduce this risk. However, the impact of TIB on memory and learning, as well as on choline acetyltransferase (ChAT) and tryptophan hydroxylase (TPH) levels in the hippocampus of aging males, is unknown. We administered TIB to aged C57BL/6J male mice at different doses (0.01 or 1.0 mg/kg per day for 12 weeks) and evaluated its effects on memory and learning and the content of ChAT and TPH. We assessed memory and learning with object recognition and elevated T-maze tasks. Additionally, we determined ChAT and TPH protein levels in the hippocampus by Western blotting. TIB administration increased the percentage of time spent on the novel object in the object recognition task. In addition, the latency of leaving the enclosed arm increased in both TIB groups, suggesting an improvement in fear-based learning. We also observed decreased ChAT content in the group treated with the 0.01 mg/kg TIB dose. In the case of TPH, no changes were observed with either TIB dose. These results show that long-term TIB administration improves memory without affecting locomotor activity and modulates cholinergic but not serotonergic systems in the hippocampus of aged male mice. Full article

The endometrium is crucial for the perpetuation of human species. It is a complex and dynamic tissue lining the inner wall of the uterus, regulated throughout a woman’s life based on estrogen and progesterone fluctuations. During each menstrual cycle, this multicellular tissue undergoes cyclical changes, including regeneration, differentiation in order to allow egg implantation and embryo development, or shedding of the functional layer in the absence of pregnancy. The biology of the endometrium relies on paracrine interactions between epithelial and stromal cells involving complex signaling pathways that are modulated by the variations of estrogen and progesterone levels across the menstrual cycle. Understanding the complexity of estrogen and progesterone receptor signaling will help elucidate the mechanisms underlying normal reproductive physiology and provide fundamental knowledge contributing to a better understanding of the consequences of hormonal imbalances on gynecological conditions and tumorigenesis. In this narrative review, we delve into the physiology of the endometrium, encompassing the complex signaling pathways of estrogen and progesterone. Full article

Background: Immunological imbalances characteristic of endometriosis may develop as early as the primary manifestations of the disease in adolescence. Objective: To evaluate subpopulation dynamics of monocytes and lymphocytes in peripheral blood and peritoneal fluid of adolescents with peritoneal endometriosis at diagnosis and after 1-year progestogen therapy. Methods: This study included 70 girls, 13–17 years old, diagnosed laparoscopically with peritoneal endometriosis (n = 50, main group) or paramesonephric cysts (n = 20, comparison group). Phenotypes of monocytes and lymphocytes of the blood and macrophages of the peritoneal fluid were analyzed by flow cytometry at diagnosis and during progestogen therapy. Results: Differential blood counts of CD16⁺ (p < 0.001) and CD86⁺ (p = 0.017) monocytes were identified as independent risk factors for peritoneal endometriosis in adolescents. During the treatment, cytotoxic lymphocytes CD56dimCD16bright (p = 0.049) and CD206+ monocytes (p < 0.001) significantly increased while CD163+ monocytes decreased in number (p = 0.017). The CD56dimCD16bright blood counts before (p < 0.001) and during progestogen therapy (p = 0.006), as well as CD206⁺ blood counts during the treatment (p = 0.038), were associated with the efficacy of pain relief after 1-year progestogen therapy. Conclusions: Adolescents with peritoneal endometriosis have altered counts of pro- and anti-inflammatory monocytes and lymphocytes both before and after 1-year progestogen therapy, correlating with treatment efficacy and justifying long-term hormonal therapy. Full article

We evaluated the long-term risks of overall cancer and all-cause mortality associated with five types of phytopharmaceuticals and the most commonly used estrogen-progestogen medications for the treatment of postmenopausal syndrome in women. Using data from Taiwan’s National Health Insurance Research Database (NHIRD) from 1 January 2000 to 31 December 2018, we conducted a 1:2 matched cohort study with 12,087 eligible patients. We compared phytopharmaceuticals -only users (n = 4029, phytopharmaceuticals group) with HRT-only users (n = 8058, HRT group) with a washout period of ≥6 months. The phytopharmaceuticals group had significantly lower risks of overall cancer and all-cause mortality than the HRT group (adjusted hazard ratio [95% confidence interval]: 0.60 [0.40–0.9] and 0.40 [0.16–0.99], respectively) after over 180 days of use. Bupleurum and Peony Formula were associated with lower risks of overall cancer and all-cause mortality (aHR: 0.57 [0.36–0.92] and 0.33 [0.11–1.05], respectively). In conclusion, phytopharmaceuticals may serve as an alternative therapy to HRT for alleviating menopausal symptoms and reducing health risks, leading to more favorable long-term health outcomes. Further randomized control trials are necessary to validate the findings of this study. 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