Tubo-ovarian cancer represents the most lethal gynecologic malignancy, and its burden is compounded by the absence of effective screening and the substantial lifetime risk carried by women with germline BRCA1 or BRCA2 pathogenic variants. While risk-reducing salpingo-oophorectomy remains the standard for prevention, conferring reduction in tubo-ovarian cancer risk and improved overall survival, it also induces premature menopause with significant effects on quality of life and bone, cardiovascular, and sexual health. These consequences have driven the exploration of alternative preventive strategies, and a paradigm shift toward individualized risk assessment. Emerging data highlight that tubo-ovarian cancer risk among BRCA pathogenic variant carriers is not uniform but influenced by gene type, variant position, family history, and modifiable factors such as parity, breastfeeding, and oral contraceptive use. Modern risk models integrate genetic, familial, and lifestyle data to refine personalized estimates and guide the timing of intervention. Concurrently, the understanding that many high-grade serous carcinomas originate in the fallopian tube has prompted evaluation of risk-reducing salpingectomy with delayed oophorectomy as a staged surgical strategy that may balance oncologic safety with preservation of hormonal function. Ultimately, management of BRCA pathogenic variant carriers must combine genomic precision, reproductive planning, and patient-centered counseling to align cancer prevention with quality of life, supporting truly individualized care in hereditary tubo-ovarian cancer risk reduction. Despite several reviews on hereditary tubo-ovarian cancer prevention, a clinically relevant gap remains in translating contemporary evidence into a practical counseling framework for women with BRCA1/2 pathogenic variants. This narrative review aims to synthesize current evidence on tubo-ovarian cancer risk assessment and risk-reducing strategies in this population, with a focus on individualized counseling and shared decision-making.

Chemotherapeutic agents used in cancer treatment cause damage to both oocytes and granulosa cells, resulting in follicle loss and consequently premature ovarian failure. In this study the animals were randomly assigned to three groups: control (n = 6), chemotherapy (n = 6), and stem cell treatment (n = 6). Ovarian failure was induced in the chemotherapy and stem cell groups by intraperitoneal administration of cyclophosphamide (200 mg/kg) on days 1 and 8. Ovarian stromal stem cells (OSSCs) were isolated from the ovaries of 4-week-old donor rats (n = 2) using the explant culture method. On day 9, isolated stromal cells were transplanted bilaterally into the ovaries of rats in the stem cell group. Surface markers were analyzed by flow cytometry in OSSCs, and their adipogenic, osteogenic, and chondrogenic differentiation potentials were evaluated under appropriate in vitro conditions. The number of follicles and the morphological features of the ovarian tissue were histologically examined using hematoxylin and eosin (H&E) staining. Caspase 3 expression in ovarian tissue was analyzed using TUNEL and immunohistochemistry methods. Flow cytometry analysis of isolated ovarian stromal cells showed that CD54, CD90 and CD45 surface markers were expressed, while CD29 was expressed at a lower level. These findings confirmed the ability of OSSCs to differentiate into adipogenic, osteogenic, and chondrogenic lineages in vitro. Follicle counting, TUNEL and immunohistochemical analysis showed that treatment with ovarian stromal stem cells significantly reduced the number of atretic follicles and increased the number of normally developing follicles in the ovaries of chemotherapy-treated rats. Our research demonstrates the therapeutic effects of (allogeneic) ovarian stromal stem cells present in their niche on ovarian toxicity induced by chemotherapy, suggesting an alternative treatment option for approaches aimed at preserving fertility.

Nutraceuticals represent promising strategies for preventing, delaying and addressing premature aging of the skin, especially as women advance in years (particularly after 30 years of age, when estrogen levels begin to decline, and remarkably after menopause when estrogen production ceases from the ovaries). This review is part of a larger project, and we present this companion review, which provides a detailed examination of the literature beyond polyphenols and/or phytoestrogens for estrogen-deficient skin. This narrative review covers the top-selling nutraceutical, collagen, along with the antioxidants, curcumin and glutathione, in women between 30 to over 65 years of age regarding their effectiveness in enhancing dermal health parameters. There were 23 clinical studies published between 2020 and 2025 that support collagen as an effective nutraceutical treatment. These studies showed improvement in various skin attributes, but investigations are lacking on collagen's effectiveness on scalp hair and nail health, which warrants further examination. Curcumin and glutathione, while these remain popular nutraceutical applications to improve skin health, had only a few clinical studies published; thus, more studies are needed to establish optimal dosing regimens and identify which combination approaches provide the most meaningful dermal benefits, especially in aging women. Trends and future directions in nutraceutical skin applications include the use of collagen (where many clinical studies have been reported), along with antioxidants and bioactives. Therefore, nutraceutical skin applications using collagen and antioxidants such as curcumin and glutathione demonstrate hopeful results for dermal antiaging effects, especially in estrogen-deficient skin. However, more investigations are warranted to expand their applications to meet the evolving dermatological challenges. Finally, there is a need to balance the psychological and ethical considerations in aesthetic medicine, distinguishing between objective beauty and subjective attractiveness, while emphasizing the importance of a patient's self-confidence in ethical practice.Graphical Abstract available for this article.

Female reproductive disorders present significant challenges worldwide. Transfer RNA-derived small RNAs (tsRNAs), a structurally diverse class of non-coding RNAs mainly comprising tRNA halves (tiRNAs) and tRNA-derived fragments (tRFs), have emerged as key regulators in human health and disease. This review outlines the biogenesis and functions of tsRNAs and summarizes their mechanistic involvement and clinical implications across a range of reproductive pathologies. In pregnancy-related complications, such as embryo implantation failure and recurrent spontaneous abortion, aberrant tsRNA profiles perturb trophoblast behavior, endometrial decidualization, and maternal-fetal crosstalk, thereby compromising placental development and pregnancy outcome. In benign gynecological conditions including premature ovarian failure and endometriosis, dysregulated tsRNAs disrupt granulosa cell survival, promote stromal proliferation, and reshape inflammatory signaling, ultimately altering follicular development and uterine homeostasis. As our understanding of tsRNA-mediated pathways deepens, these molecules offer promising potential as diagnostic biomarkers and therapeutic targets for precision medicine in female reproductive disorders.

Premature ovarian insufficiency (POI) is defined as the loss of ovarian function before the age of 40 years, characterized by elevated gonadotrophin and low oestradiol concentrations. Although the probability of pregnancy is markedly reduced in women with POI, natural conception remains possible, with reported rates of approximately 5-10%. Premature ovarian insufficiency has been associated with increased risks of cardiovascular disease, autoimmune disorders and accumulation of unrepaired DNA damage. On the basis of these associations, a higher risk for developing early pregnancy complications, late pregnancy complications, or both, was hypothesized. Obstetric and neonatal risks in this population, however, have received limited attention to date. The aim of this systematic review was to summarize and evaluate studies primarily investigating pregnancy outcomes in women with idiopathic POI compared with women without POI, following both natural and assisted conceptions. Despite screening 3640 articles, none met predefined inclusion criteria. Nevertheless, comparison of available data on POI pregnancies with outcomes in the general population suggests an increased risk of early pregnancy loss, after (non-) donor ART. Given that POI is a complex condition with profound effects on physical and mental health, it is essential to further explore its potential effect on pregnancy. The need for well-designed future studies in this field, is therefore, emphasized.

Premature ovarian failure (POF) is a significant cause of infertility and is often linked to autoimmune aetiologies. Lipopolysaccharide (LPS)-induced inflammation is a well-established model of autoimmune POF in rodents. Immunomodulatory treatments involving corticosteroids, frankincense, and targeted secondary antibodies have been hypothesised to mitigate the autoimmune response, reduce anti-ovarian antibody (AOA) levels, and restore ovarian function in an LPS-induced POF rat model. A POF model was established in female albino rats via the intraperitoneal injection of LPS. The rats were then divided into groups that received no treatment (LPS control), dexamethasone (DEX-treated LPS-treated rats), methylprednisolone (MP-treated LPS-treated rats), frankincense (Frankincense-treated LPS-treated rats), or secondary anti-ovarian antibodies (secondary Ab-treated LPS-treated rats) for 3 to 4 weeks. The serum levels of AOA, 17β-oestradiol, follicle-stimulating hormone (FSH), and luteinising hormone (LH) were assayed via commercial enzyme-linked immunosorbent assay (ELISA) kits. Ovarian tissues were examined histopathologically to assess structural damage and recovery. LPS induction successfully created a POF phenotype, as evidenced by significantly elevated AOA levels (P < 0.001), reduced 17β-oestradiol (P < 0.001), elevated FSH/LH (P < 0.001 and P < 0.05, respectively), and severe histopathological damage, including follicular atresia. All the treatments restored 17β-oestradiol levels. Secondary antibody therapy was most effective, normalising all hormonal parameters, significantly reducing AOA levels, and demonstrating complete histological recovery with healthy follicles and corpora lutea. MP potently suppressed AOA but paradoxically elevated FSH, without improving ovarian histology. DEX and frankincense showed intermediate efficacy, improving some hormonal and serological markers but failing to achieve full histological restoration. These findings demonstrate that targeted immunotherapy using secondary antibodies is superior to broad immunosuppression or anti-inflammatory treatment for restoring ovarian function in patients with autoimmune POF. While corticosteroids effectively reduce AOA titres, they may not reverse ovarian damage and can disrupt the hormonal balance. This underscores the need for precise, biomarker-guided therapies over nonspecific immunosuppression in patients with autoimmune ovarian insufficiency.

The ovaries are vital components of the female reproductive system. Ovarian aging, driven by oxidative stress, chronic inflammation and hormonal dysregulation, severely compromises female fertility. The receptor for advanced glycation end products (RAGE) serves as a critical regulator of ovarian physiology and pathology. linking metabolic dysfunction to reproductive decline. This Review synthesizes evidence that RAGE hyperactivation, during the process of ovarian aging, disrupts folliculogenesis, granulosa cell function and steroidogenesis via MAPK-ERK, PI3K-AKT-mTOR and NF-κB pathways, exacerbating conditions such as premature ovarian failure, polycystic ovary syndrome and ovarian cancer. Furthermore, we summarizes existing therapeutic strategies targeting RAGE and underscores their potential in mitigating ovarian aging and treating ovarian pathologies, providing novel perspectives for preserving female reproductive capacity. We highlight therapeutic strategies targeting RAGE, including small-molecule inhibitors (Azeliragon and FPS-ZM1), soluble RAGE decoys and natural compounds, which show promise in restoring ovarian reserve and hormonal balance in preclinical models. These interventions mitigate advanced glycation end products (AGE)-RAGE-induced damage, offering novel avenues to preserve fertility. Beyond reproductive health, RAGE's role in aging and metabolic disorders underscores its potential as a cross-disciplinary biomarker and therapeutic target. By bridging molecular mechanisms with clinical applications, this work provides a framework for developing precision therapies to combat ovarian aging, with implications for endocrinology, oncology and geroscience.