Premature ovarian insufficiency (POI) is characterized by impaired ovarian endocrine function and reduced ovarian reserve.

Premature ovarian insufficiency (POI) and early menopause (EM) affect millions of women worldwide. Compared with normal menopause, they confer a longer duration of estrogen deficiency and are associated not only with a shorter lifespan, but with a reduced healthspan, owing to an increased risk of cardiovascular, skeletal, cognitive and psychological morbidity, and sexual health concerns. Therefore, interventions in POI/EM represent some of the most actionable opportunities to reduce long-term disability and promote healthy longevity. However, current approaches to hormone therapy (HT) in POI/EM remain fragmented, delayed, and overly influenced by paradigms derived from older postmenopausal populations. We propose a shift toward a life-course model of care. POI and EM should no longer be managed as variants of menopause at normal age but recognized as chronic endocrine conditions and sentinel events for accelerated aging in women. HT should be reframed as a hormonal replacement aimed at preventing long-term disability. Timely initiation, adequate dosing, and long-term continuation of HT should be considered foundational to POI/EM care, alongside integrated preventive strategies. FIGO and IMS, therefore, call for a globally coordinated effort to strengthen awareness, professional education, and research on POI/EM, and to ensure equitable access to multidisciplinary care, with the goal of improving women's health and supporting the long-term sustainability of healthcare systems.

Premature ovarian insufficiency (POI) and early menopause (EM) affect millions of women worldwide. Compared with normal menopause, they confer a longer duration of estrogen deficiency and are associated not only with a shorter lifespan, but with a reduced healthspan, owing to an increased risk of cardiovascular, skeletal, cognitive and psychological morbidity, and sexual health concerns. Therefore, interventions in POI/EM represent some of the most actionable opportunities to reduce long-term disability and promote healthy longevity. However, current approaches to hormone therapy (HT) in POI/EM remain fragmented, delayed, and overly influenced by paradigms derived from older postmenopausal populations. We propose a shift toward a life-course model of care. POI and EM should no longer be managed as variants of menopause at normal age but recognized as chronic endocrine conditions and sentinel events for accelerated aging in women. HT should be reframed as a hormonal replacement aimed at preventing long-term disability. Timely initiation, adequate dosing, and long-term continuation of HT should be considered foundational to POI/EM care, alongside integrated preventive strategies. FIGO and IMS, therefore, call for a globally coordinated effort to strengthen awareness, professional education, and research on POI/EM, and to ensure equitable access to multidisciplinary care, with the goal of improving women's health and supporting the long-term sustainability of healthcare systems.

Menstrual patterns can indicate overall health and reflect changes in endocrine, metabolic, or other systemic functions. Primary amenorrhea, defined as the lifelong absence of menses, warrants evaluation by age 15 years or 3 years postthelarche. Secondary amenorrhea is defined as the cessation of previously regular menses for 3 months or irregular menses for 6 months. Evaluation begins with a focused medical history, including prior menstrual patterns; eating and exercise habits; psychosocial stressors; medication use; chronic illness; and neurologic, vasomotor, or hyperandrogenic symptoms. Physical examination should assess anthropometric trends and pubertal development. Routine laboratory testing includes pregnancy testing and serum estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone (thyrotropin) levels. Additional testing, including karyotyping, serum androgen evaluation, and pelvic or brain imaging, is individualized. Functional hypothalamic amenorrhea may indicate treatment for underlying disordered eating or low bone density. Patients with premature ovarian insufficiency benefit from hormone therapy until the average age of natural menopause. Addressing lifetime metabolic disease and endometrial cancer risk is necessary for patients with polyendocrine metabolic ovarian syndrome (formerly polycystic ovary syndrome).

Long-chain chlorinated paraffins (LCCPs) accumulate in reproductive organs due to their high persistence and bioaccumulation potential; however, the molecular mechanisms underlying their ovarian toxicity remain unclear. In this study, we used primary mouse granulosa cells, a human SVOG cell line, and an oral exposure model in female mice to systematically evaluate the ovarian damage effects of LCCPs and investigate the underlying signaling pathways. The results showed that concentrations of 0.02-2 µg/mL of LCCPs concentration-dependently reduced granulosa cell survival rates (by 12%-58%, P < 0.05), while significantly upregulating oxidative stress (MDA, ROS), inflammatory cytokines (IL-6, TNF-α), and aging markers (SA-β-gal activity). In vivo exposure led to morphological degeneration of ovarian tissue and a reduction in the number of primordial follicles, accompanied by decreased serum estradiol and elevated follicle-stimulating hormone (FSH) levels; these changes resemble the phenotype of clinical ovarian dysfunction. At the mechanistic level, LCCPs induce excessive mitochondrial fission by blocking the interaction between Drp1 and Parkin, leading to the leakage of mitochondrial DNA into the cytoplasm, which in turn activates the cGAS-STING pathway and ultimately drives granulosa cell senescence. These findings reveal a novel mechanism by which LCCPs mediate ovarian toxicity via the "excessive mitochondrial fragmentation- mtDNA leakage- cGAS- STING- cellular senescence" axis, providing direct experimental evidence for assessing the risks of persistent organic pollutants to female reproductive health.

Given concerns about the reproductive safety of aspartame, this study investigated aspartame-induced premature ovarian failure (POF) using integrated computational biology, in vitro, and in vivo approaches. Network toxicology identified 182 overlapping targets, which were mainly enriched in oxidative stress (OS), apoptosis, and the PI3K/AKT/mTOR pathway. Molecular dynamics (MD) simulations initially predicted that SIRT1 had the highest binding affinity for aspartame, and this interaction was further validated by surface plasmon resonance (SPR) analysis. In vitro experiments using KGN cells showed that aspartame suppressed cell proliferation in a time- and concentration-dependent manner. RNA sequencing (RNA-seq) revealed SIRT1 downregulation and enrichment of related pathways. Further in vitro experiments demonstrated that aspartame inhibited SIRT1 and the PI3K/AKT/mTOR pathway, increased ROS levels, and promoted apoptosis; these effects were reversed by SIRT1 overexpression. Parallel in vivo studies showed that oral administration of aspartame to rats at 30-120 mg/kg for 8 weeks disrupted the estrous cycle, induced hormonal imbalance, caused follicular dysplasia, increased follicular atresia, and reduced ovarian reserve. Ovarian immunohistochemistry (IHC) further confirmed apoptotic damage. To further clarify the driving role of OS, assays utilizing serum from aspartame-treated mice combined with N-acetylcysteine (NAC) showed that ROS elevation and subsequent apoptosis were significantly reversed by NAC treatment. Collectively, these findings suggest that aspartame exposure contributes to POF, with direct suppression of the SIRT1/PI3K/AKT/mTOR pathway representing a key molecular mechanism underlying its intrinsic toxicity and aggravating OS-related apoptosis. This study provides mechanistic evidence for the reproductive toxicity of aspartame and supports the need for further risk assessment and exposure control to reduce the risk of POF.

We report a woman in her 20s with congenital adrenal hyperplasia (CAH) due to a clinical diagnosis of 11β-hydroxylase deficiency, bilateral ovarian adrenal rest tumours (OARTs), autoimmune Addison's disease and premature ovarian insufficiency. Despite the combination of CAH and OARTs, she conceived spontaneously twice, with complete regression of the tumours under glucocorticoid therapy. Years later, she developed an Addisonian crisis confirmed by positive 21-hydroxylase antibodies and subsequently manifested ovarian failure and mineralocorticoid deficiency. This case illustrates the rare coexistence of distinct adrenal and ovarian pathologies, highlights the potential reproductive impact of OARTs and underscores the need for further study and standardised management strategies.

Platelet-rich plasma (PRP) is an autologous regenerative therapy investigated for improving endometrial receptivity, ovarian function, and reproductive outcomes. To address inconsistent findings across existing reviews, we conducted an umbrella review of systematic reviews and meta-analyses identified from PubMed, Embase, Web of Science, and the Cochrane Library, with evidence appraised using AMSTAR-2 and GRADE. Twenty-one reviews were included. In women with recurrent implantation failure, intrauterine PRP was associated with improved live birth, clinical pregnancy, and biochemical pregnancy rates. Similar benefits were observed in women with previous implantation failure and in assisted reproductive technology (ART) populations. PRP also modestly increased endometrial thickness and implantation rates. In women with thin endometrium or intrauterine adhesions, PRP improved pregnancy outcomes and reduced cycle cancellation, while miscarriage rates were largely unchanged. Intra-ovarian PRP improved ovarian reserve markers, hormone profiles, oocyte yield, and embryo quality in women with poor ovarian response, premature ovarian insufficiency, or diminished ovarian reserve, although effects on pregnancy and live birth were variable. Overall, PRP shows potential benefits, but the certainty of evidence ranged from very low to moderate due to heterogeneity and methodological limitations. High-quality randomized controlled trials are required to confirm efficacy and guide clinical practice.

The management of menopausal symptoms in healthy women carrying BRCA1 or BRCA2 mutations is clinically challenging, particularly in those undergoing risk-reducing salpingo-oophorectomy. This preventive surgery is recommended because it lowers the risk of ovarian cancer, halves the risk of breast cancer and decreases the risk of all-cause mortality; nevertheless, it induces premature menopause, which does have health consequences. Given the negative impact of premature surgical menopause on BRCA1 and 2 mutation carriers' health and quality of life, this population could greatly benefit from hormone replacement therapy. However, its use in this context remains limited, mainly due to patients' and physicians' concerns about its oncological safety. Current evidence suggests that a short course of hormone replacement therapy does not increase breast cancer risk in BRCA mutation carriers after risk-reducing salpingo-oophorectomy. Therefore it can be proposed to BRCA mutation carriers until the age of natural menopause. This review represents a guide to daily practice by answering questions - the 5 Ws (why, when, who, what and where) and 2 Hs (how and how much) - to help physicians in their counselling on hormone replacement therapy and its prescription for this special population.

Plastics are ubiquitous in the environment and are widely used in food packaging, medicine, agriculture, construction and other sectors. However, the plasticizers they contain pose a substantial threat to environmental safety and human health. Phthalates represent the most important class of plasticizers and are classified as endocrine-disrupting chemicals (EDCs), capable of causing adverse effects even at very low exposure levels. Extensive in vitro and in vivo studies have demonstrated that phthalates and their metabolites exhibit reproductive toxicity, leading to reduced sperm motility and count, hormonal dysregulation, ovarian failure, preterm birth and other detrimental outcomes. This review synthesizes current evidence on the association between phthalate exposure and various reproductive system disorders. Epidemiological studies show that phthalate exposure is linked to impaired sperm quality, prostate disease and erectile dysfunction in males, suggesting a contributing role in the pathogenesis of infertility. However, the association with shortened anogenital distance remains unclear. In females, phthalate exposure has been associated with endometriosis, polycystic ovary syndrome, premature ovarian failure, infertility and miscarriage, although the epidemiological evidence is inconsistent. In conclusion, paying attention to the reproductive health risks posed by phthalate exposure is of critical importance, particularly for vulnerable groups including women of childbearing age, pregnant women, and children.