Ovarian Failure Research Articles

An overview of different methods to establish a murine premature ovarian failure model.

Premature ovarian failure (POF)is defined as the loss of normal ovarian function before the age of 40 and is characterized by increased gonadotropin levels and decreased estradiol levels and ovarian reserve, often leading to infertility. The incomplete understanding of the pathogenesis of POF is a major impediment to the development of effective treatments for this disease, so the use of animal models is a promising option for investigating and identifying the molecular mechanisms involved in POF patients and developing therapeutic agents. As mice and rats are the most commonly used models in animal research, this review article considers studies that used murine POF models. In this review based on the most recent studies, first, we introduce 10 different methods for inducing murine POF models, then we demonstrate the advantages and disadvantages of each one, and finally, we suggest the most practical method for inducing a POF model in these animals. This may help researchers find the method of creating a POF model that is most appropriate for their type of study and suits the purpose of their research.

Ovulatory Failure in Mares During Breeding Seasons

Abstract In the years 2022 and 2023 we investigated the prevalence of the ovulatory failure in 133 mares of different breed, 3 to 24 years old, brought to the Equine clinic of the University of Veterinary Medicine and Pharmacy (UVMP) in Košice. Our research involved the monitoring of the reproduction cycle in these mares with the aim to determine the prevalence of ovulatory failure during the breeding season, focusing on certain specific parameters that were considered sufficiently relevant with respect to the development of such failure. These parameters included environmental temperature and the amount of daylight the mares were exposed to, attributable to the months of the breeding season. In addition, we also evaluated the size of pre-ovulatory follicles and the influence of age of the investigated mares. During the mentioned years, one of the ovulatory failures occurred in 17 out of 133 mares (12.78 %). Examination by ultrasonography (USG) and the subsequent analysis of the occurrence of failures in relation to the investigated parameters allowed us to conclude that the length of daylight, age, and environmental temperature were the most important factors. Our observations indicated that the 15–16 h category of daylight presented the highest risk of development of cycle disorders with the most rapid increase observed for HAF. With respect to age, the highest occurrence of ovulatory failures was observed in the category of 15–24 years. The external temperature in the range of 18.1–23.0 °C affected the most the development of cycle disorders. Again, the effect was most evident with respect to HAF. This resulted in our recommendations for horse breeders that they should manage reproduction of their mares in a way so that the receptive phase of the cycle does not occur in the months during which the daylight length and environmental temperatures support ovulatory failure. We also recommend that if the owner′s wish is to keep in the breeding the mares older than 15 years, regular thorough gynaecological examination of these animals should be ensured, aimed at early diagnosis of ovulatory failure.

Individualized responses to acupuncture in premature ovarian insufficiency: A study protocol for a nested case-control trial with transcriptome analysis

BackgroundPremature ovarian insufficiency (POI), a modifiable cause of infertility with substantial implications for women's well-being, prompts the exploration of efficacious adjunctive treatments. Acupuncture emerges as a promising therapeutic avenue; however, the nuanced effects of acupuncture in POI warrant more comprehensive investigation. The intricate mechanisms dictating individualized responses remain elusive. This trial seeks to assess the effectiveness of acupuncture as an adjunctive treatment for POI, concurrently delving into the impact of transcriptome analysis on peripheral blood to unravel the underpinnings of these individual variations. The overarching objective is to enrich our comprehension of acupuncture's therapeutic potential in the context of POI, with a view to advancing holistic patient care. Methods/designConstituting an open-label, nested case-control study, this research endeavors to enroll 108 women diagnosed with POI. Participants will be randomly assigned in a 1:1 ratio to either the study group or the control group, each comprising 54 subjects. Ten patients from each group meeting specific criteria will partake in transcriptome analysis. An additional 10 subjects meeting the study criteria will form a healthy control group. The study group will exclusively undergo acupuncture treatment, while the control group will solely receive Fenmutong. Acupuncture sessions, administered thrice weekly across three menstrual cycles from the fifth day of menstruation, constitute the intervention. Primary outcome measurement rests on Follicle-Stimulating Hormone (FSH) levels, supplemented by secondary assessments encompassing biometric features, hormone biomarkers, anxiety and depression scores, and transcriptome analysis. Baseline measurements precede intervention, with post-intervention evaluations following. The study endeavors to discern specific genes linked to individualized responses to acupuncture. Data analysis, employing SPSS 25.0 software, incorporates a meticulous examination of peripheral blood samples for transcriptome analysis. The investigation aspires to shed light on genetic determinants influencing the effects of acupuncture on women with POI, thereby fostering elevated standards in patient care and management. DiscussionThis study pivots on the principal objective of scrutinizing the efficacy of acupuncture as an adjunctive treatment for POI. Beyond effectiveness, it undertakes an exploration of the intricate mechanisms underlying the diverse responses exhibited by individuals in the context of acupuncture, augmenting the depth of understanding in this therapeutic domain.

Breast cancer survivorship among younger patients: challenges and opportunities-narrative review.

Young women with breast cancer (YWBC) face unique survivorship challenges due to being diagnosed at a more vulnerable stage in life and receiving gonadotoxic and/or antiestrogen therapy during their reproductive years. The purpose of this article is to elaborate on these challenges and demonstrate how specialized supportive care programs tailored specifically for YWBC, can greatly facilitate the provision of interventions to address these challenges. The databases used were PubMed and Medline. Articles included those that involve young women with breast cancer and survivorship care needs. Compared to older breast cancer patients, YWBC generally require more aggressive treatments and are more likely to have a hereditary basis for their disease. Common challenges include childbearing concerns, premature menopause, body image issues, excessive fear of cancer recurrence, difficulties with intimate relationships, and financial toxicity. A possible solution to addressing these needs are longitudinal care in a specialized supportive care program, such as the PYNK Program for Young Women with Breast Cancer in Toronto, Ontario, Canada. Examples of such interventions include fast-tracking fertility preservation, aggressive management of symptoms of iatrogenic menopause, peer support groups, as well as individualized psycho-social support for the patient and her family. By addressing the unique needs of this population, supportive care programs can play a crucial role in empowering young women with breast cancer to cope with the physical, emotional, and practical challenges they may face during and after treatment. The limitation lies in resource availability and funding for sustainability. Ongoing research is required to better understand the needs of YWBC patients in survivorship and ensure the sustainability of programs designed to address these challenges.

Association of Physical Activity Levels with Coronary Artery Disease Risk Factors in Middle aged (40-55) Bangladeshi Women

Background: A sedentary lifestyle is associated with increased risk of Coronary Artery Disease (CAD) in women. At least 150min/wk of moderate activity or 75min/wk of vigorous activity or combination is recommended by American Heart Association (AHA) for primary prevention of CAD. The purpose of this study was to assess the physical activity levels of middle aged women and to find out the association of CAD risk factors with physical activity level. Methods: This cross-sectional analytical study was conducted in Dhaka Medical College Hospital (DMCH) cardiology OPD from May 2019 to April 2020. We interviewed 249 middle aged women (40-55) who attended our OPD during the study period and fulfilled the exclusion and inclusion criteria. Global Physical Activity Questionnaire (GPAQ) was used to assess physical activity level. Blood pressure and BMI was measured. OGTT and fasting lipid profile was done. Subjects with low physical activity was assigned in Group I (n=152), moderate activity in group II (n= 93) and high activity in group III (n= 4). Association between the physical activity levels and presence of CAD risk factors like DM, HTN, dyslipidemia and obesity was evaluated. Results: In this study we found that most of the study subjects (61.0%) were in low active group. Overall 70.2% women were menopausal and premature menopause (≤50 years) was found in 47.8% of subjects. Mean age of menopause was 47±3.8; (44-53) years and mean duration of menopause was 3.1±0.5 years. Overall prevalence of DM, HTN, obesity and dyslipidemia was 62.2%, 50.6%, 39.8% and 53.4% accordingly. Women in low active group were having significant higher proportion of DM (52.6%), HTN (65.8%), obesity (57.9%) and dyslipidemia (75.7%) in comparison to moderate active group. Only 4 women were in highly active group and none of the CAD risk factors was present among them. Bangladesh Heart Journal 2024; 39(2): 127-137

Abstract P171: 2-Methoxyestradiol By Inhibiting Central Action of 12S-Hydroxyeicosatetraenoic Acid Protects Ovariectomized Mice From Hypertension

Previously, we reported that 17β-estradiol (E2)- cytochrome P450 (CYP) 1B1-generated metabolite 2-methoxyestradiol (2-ME) in the paraventricular nucleus (PVN) protects from angiotensin (Ang) II-induced hypertension. Recently, we showed that intracerebroventricular (ICV) administration of 12(S)-hydroxyeicosatetraenoic acid (12S-HETE), an arachidonic acid-12/15-lipoxygenase (LO) metabolite produces a greater increase in blood pressure (BP) in ovariectomized (OVX) than intact LO knockout (KO) mice. These observations led to the hypothesis that 2-ME protects from Ang II-induced hypertension by inhibiting the production and action of 12S-HETE in the brain in female mice. ICV 2-ME (1.5 µg/2 µL/ alternate day) but not its vehicle (20% w/v hydroxypropyl-β-cyclodextrin) minimized the effect of Ang II (700 ng/kg/min, subcutaneous, osmotic pump, two weeks) to increase mean arterial blood pressure (MAP: Day 0 vs Day 12; 105±3 to 121±2 vs 105±3 to 153±8, mmHg) measured by radiotelemetry, urinary norepinephrine level (ELISA, 445±27 vs 898±20, ng/mL), lo mRNA expression (RT-PCR, 1.5±0 vs 2.0±1, arbitrary unit), 12S-HETE level (ELISA, 136±26 vs 285±44, pg/mg protein), and GFAP+ (immunostaining, astrocyte marker, 35±3 vs 67±3, number of cells per PVN section) cells in PVN and kidney fibrosis (histochemical-staining, 4.0±0.3 vs 9.8±0.7, arbitrary unit) in OVX-LOKO mice transduced with ICV-adenovirus-LO-DNA (1.28X10 11 pfu/ml, 2 µL, single injection) that have 12S-HETE in the brain (PVN) but not in plasma (n=4/group; P<0.05). ICV siRNA (0.4 nM, 2 µL, single injection) against 12S-HETE receptors LTB4 and GPR31 minimized Ang II-induced increased systolic BP measured by tail-cuff in intact CYP1B1 KO mice that have E2 but lacks 2-ME (mmHg, control: 108±3 to 175±6, siRNA-LTB4r2: 110±5 to 141±3, siRNA-GPR31: 114±1 to 145±2; n=8 per group). Moreover, the actions of ICV 12S-HETE (50 ng/2 µL every 3rd day) to enhance the effect of Ang II-induced increase in MAP were also minimized by ICV siRNA-LTB4 and GPR31 respectively in OXV-LOKO mice (mmHg, control: 102±2 to 168±1, siRNA-LTB4r2: 101±2 to 122±6, siRNA-GPR31: 101±3 to 129±3; n=4 per group). These data suggest that E2-CYP1B1 metabolite 2-ME, by inhibiting the production and action of 12S-HETE in the brain via LTB4r2 and GPR31 receptors protect from Ang II-induced hypertension in female mice. Thus, 2-ME and/or 12S-HETE receptor blockers could be useful for treating hypertension and its pathogenesis in females with ovarian failure.

Preliminary Report of the Effects of Platelet-Rich Plasma on the Ovarian Function and Oocyte Quality in Women with Ovarian Failure

This study investigated the effects of platelet-rich plasma (PRP) treatment on ovarian function and pregnancy outcomes in three patients with severe reduction of ovarian reserve. The patients had previously undergone multiple cycles of assisted reproductive technology (ART) without favorable results. Prior to PRP treatment, follicle-stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH) levels were assessed. PRP was administered through intraovarian injection. Hormonal assessments were performed at 6–7 months after the first PRP injection. The results showed major improvements in ovarian function, as evidenced by decreased FSH levels and increased AMH levels in all three patients. The number of mature oocytes retrieved per cycle and the ovum-to-blastocyst rate were also improved. All the patients achieved successful pregnancies and gave birth to healthy infants. These findings suggest that PRP may enhance ovarian function, oocyte quality, and pregnancy outcomes in patients with severely reduced ovarian reserve. Further research is necessary to validate these results and explore the underlying mechanisms.

A local audit evaluating bone health in patients with functional hypothalamic amenorrhoea secondary to an eating disorder and a review of the application of hormone therapy in this clinical setting.

It is widely known that estrogen has a fundamental role to play in skeletal homeostasis. In the most reductionist sense, the action of estrogen can be surmised as anti-resorptive. Estrogen prevents the break-down of bone. It therefore follows that estrogen deficiency states, such as the menopause and functional hypothalamic amenorrhoea (FHA), are often characterised by increased bone remodelling and disrupted skeletal homeostasis. FHA is the cessation of menstruation secondary to abnormal signalling between the hypothalamus and pituitary gland due to deficient pulsatile secretion of Gonadotrophin Releasing Hormone (GnRH). Functional hypothalamic amenorrhoea is frequently a consequence of women suffering with eating disorders. The development of FHA secondary to eating disorders is an evolutionary adaptive response to chronic metabolic energy deficiency. Fundamentally, preservation of life is biologically prioritised over dispensable physiological process such as reproduction. Consequently, the hypothalamic-pituitary-ovarian (HPO) axis fails, which disrupts menstrual function and ovulation, culminating in a state of estrogen deficiency. One of the most important and long-lasting deleterious consequences of FHA is disrupted skeletal homeostasis and bone loss. Estrogen replacement, most commonly in the form of combined hormone replacement therapy (HRT) or the combined oral contraceptive pill (COCP), is advised for women with an early menopause to prevent bone loss. Arguably, estrogen replacement should also be utilised in the context of FHA. However, the optimum estrogen regime for women with FHA remains under-researched and so management is not evidence-based.

ЭКСПЕРИМЕНТАЛЬНЫЕ МЕТОДЫ МОДЕЛИРОВАНИЯ ПРЕЖДЕВРЕМЕННОЙ НЕДОСТАТОЧНОСТИ ЯИЧНИКОВ: ПРЕИМУЩЕСТВА И НЕДОСТАТКИ

Premature ovarian insufficiency (POI) is a disorder of ovarian function in women under 40 years of age accompanied by amenorrhea or oligomenorrhea for more than 4-6 months with biochemical confirmation of follicle-stimulating hormone (FSH) levels >25 IU/L when assessed twice at 4-week intervals. There are four main types of mouse models of PND: the "chemotherapy" model, the "autoimmune" model, the "psychological stress" model, and the "natural aging" model. The most commonly used is the chemotherapeutic model of NPT induced by cyclophosphamide. Also, such a model can be obtained by induction with trypterigium glycosides (TG), busulfan (BF), DOX, etc. An autoimmune model is developed using ZP3 glycoproteins, a stress mouse model of PNJ is obtained using CUMS, MS, etc. methods. By subcutaneous injection of D-Gal, a natural aging model is generated. Each has its own advantages and disadvantages, relative to ideal criteria mouse models of premature ovarian failure. Based on such considerations, chemotherapeutic models are leading so far, but this mode of induction has a number of side effects such as myelosuppression and bleeding. The aim of this review is to analyze the current data on different murine models of PND, their advantages disadvantages, as well as subtypes and modes of induction.

Icariin inhibits cisplatin-induced ovarian toxicity via modulating NF-κB and PTEN/AKT/mTOR/AMPK axis.

Cisplatin (CP) is a highly effective broad-spectrum chemotherapeutic agent for several solid tumors. However, its clinical use is associated with ovarian toxicity. Icariin (ICA) is a bioactive flavonoid of Epimedium brevicornum with reported protective activities against inflammation, oxidative stress and ovarian failure. This study aimed to explore the protective effects of ICA against CP-associated ovarian toxicity in rats. Rats were randomized into five groups and treated for 17 days: control, ICA (10 mg/kg/day, for 17 days. p.o.), CP (6 mg/kg, i.p. on days 7 and 14), CP + ICA (CP 6 mg/kg i.p. on days 7 and 14 and ICA 5 mg/kg p.o. daily), and CP + ICA (CP 6 mg/kg i.p. on days 7 and 14 and ICA 10 mg/kg p.o. daily). Our results indicated that ICA effectively improved ovarian reserve as indicated by attenuating CP-induced histolopathological changes and enhancing serum anti-müllerian hormone (AMH). Furthermore, co-administration of ICA with CP showed restoration of the oxidant-anti-oxidant balance in ovarian tissues, evidenced by decreased malondialdehyde (MDA) concentrations and elevated superoxide dismutase (SOD) and catalase (CAT) activities. Also, ICA suppressed ovarian inflammation as evidenced by down-regulation of the expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nuclear factor kappa B (NF-κB). ICA inhibited ovarian apoptosis in CP-treated rats by down-regulation of CASP3 and Bax and up-regulation of Bcl-2 mRNA expression. Further, ICA enhanced PTEN, p-AKT, p-mTOR, and p-AMPKα expression. In conclusion, ICA possesses a protective activity against CP-induced ovarian toxicity in rats by exhibiting antioxidant, antiinflammatory, anti-apoptotic activities and modulating NF-κB expression and PTEN/AKT/mTOR/AMPK axis in ovarian tissues.

Serum anti-Mullerian hormone levels in Turkish girls aged 18 and younger for ovarian reserve determination

Our aim was to show that anti-Mullerian hormone (AMH) may be used as a quantitative marker of ovarian reserve in Turkish girls aged 18 years and younger and establish the reference values for AMH in Turkish girls. This retrospective study included girls between 8-18 years old, without premature ovarian failure or without genetic factors resulting in ovarian dysgenesis. Blood specimens were collected after overnight fasting early in the morning during the early follicular phase. Measurement of serum levels of gonadotropins and AMH was done. Mean serum AMH levels of different age groups and best fitting curve representing AMH percentiles (10th, 25th, 50th, 75th, 90th) were calculated. In total 785 girls with a mean age of 16.16±1.90 years were included, divided into seven age groups. The mean serum AMH level for the total cohort was 5.20±4.19 ng/mL. There was a significant difference between the mean values of AMH in age groups as follows: ≤12 and 17-≤18 (p=0.011). The best fitting curves for AMH percentiles were 4th order polynomial functions. There was a significant correlation between AMH and age and follicle stimulating hormone levels (r=0.148, p<0.001 and r=-0.092, p=0.010). Our results reflect the real-life data for serum AMH values in Turkish girls. Our nomogram may be useful for counseling adolescents about their ovarian reserve and diagnosing other gynecological diseases. A longitudinal study is necessary for improving the predictive value of AMH values in girls aged 18 and younger.

Association of Polymorphisms in FSHR, ESR1, and BMP15 with Primary Ovarian Insufficiency and Meta-Analysis.

Primary ovarian insufficiency (POI) can lead to menstrual disturbance, resulting in ovarian dysfunction before age 40. Prevalence of POI is usually less than 1%; however, ethnicity or population characteristics may affect prevalence. POI is a heterogeneous disease that results from abnormalities in immunological and hormonal factors. Genetic factors can also contribute to POI. Here, we examine FSHR, ESR1, and BMP15 polymorphisms in patients with POI, and controls. We examined a hormonal gene that is important for pregnancy, follicle-stimulating hormone receptor (FSHR), as well as estrogen receptor 1 (ESR1), and associated it with FSHR expression, ovulation rate, and bone morphogenetic protein 15 (BMP15). We examined 139 Korean patients under age 40 with POI, and 350 Korean control participants without POI. Genotyping was performed by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan assays. Each identified genotype was subjected to statistical analysis to determine the odds ratios (ORs) and 95% confidence intervals (CIs). In combination genotype analyses, FSHR rs6165 A > G combined with ESR1 rs9340799 A > G, AG/GG (OR: 5.693; 95% CI: 1.088-29.792), as well as FSHR rs6166 A > G combined with ESR1 rs9340799 C > T, AG/GG (OR: 5.940; 95% CI: 1.134-31.131), were significantly associated with POI prevalence. Furthermore, an FSHR rs6165 A > G and BMP rs17003221 C > T, AG/CC combination was associated with POI prevalence (OR: 1.874; 95% CI: (1.059-3.316; p-value: 0.031)). In meta-analysis, FSHR rs6165 AA vs. AG + GG is associated with POI (p = 0.0013), and ESR1 rs2234693 AA vs. AG + GG is also associated with POI (p = 0.0101). Here, we compared the genotypes of FSHR, ESR1, and BMP15 in patients with POI, and controls. We found significant differences in genotype combinations between polymorphisms in FSHR and other genes. Through meta-analysis, we found that ESR1 rs9340799 and rs2234693 are associated with POI prevalence, and that BMP15 rs17003221 increases POI risk. These findings help to improve POI diagnosis in Korean women.

A Review of the Types of Chemotherapy Drugs Used to Induce Premature Ovarian Failure in Mice

Introduction: The most common complication of chemotherapy is infertility due to premature ovarian failure (POF). POF is defined as the loss of normal ovarian function before age 40, characterized by increased gonadotropin levels, decreased estradiol levels, and diminished ovarian reserve, often leading to infertility. Despite the high impact of POF on general health and quality of life, the pathophysiology of this disease is unclear. For this purpose, animal models provide us with the opportunity to hypothetically investigate the pathogenesis of the disease comprehensively. The most common method of creating an animal model of premature ovarian failure is the use of chemotherapy drugs. In this study, the types of chemotherapy drugs and the relevant molecular pathways that play a role in creating the premature ovarian failure model in mice will be investigated Conclusion: According to the studies, cyclophosphamide drug is introduced as the most common gonadotoxic drug in order to induce POF model in mice.

Metabolic Risk in Patients with a Diminished Ovarian Reserve and Premature Ovarian Insufficiency.

Objective: Diminished ovarian reserve (DOR) and premature ovarian insufficiency (POI) represent conditions of different severity, characterized by an earlier-than-expected decrease in ovarian activity. The present study aims to compare metabolic disturbances between women with DOR and patients with POI from a different origin. Materials and methods: A total of 226 women (28 healthy women; 77 individuals with DOR, and 121 patients with POI/36 with Turner syndrome [TS] and 85 with non-TS POI/) have been studied retrospectively. Data concerning anthropometric indices, and metabolic parameters were collected. Results: Patients with DOR, non-TS POI, and TS had increased blood pressure and liver enzymes, pronounced insulin resistance, and worse lipid profiles than controls (p < 0.008 for all). TS patients had significantly higher ASAT, GGT, and TSH levels compared to non-TS POI and DOR individuals. The prevalence of type 2 diabetes tended to be higher in TS women compared to other groups. The prevalence of previously diagnosed polycystic ovarian syndrome was lower in the non-TS POI patients than in the DOR patients (p = 0.005). Conclusions: patients with decreased ovarian function suffer from insulin resistance, abnormal lipid profile, and subtle hepatic disturbances, irrespective of the severity of the condition and the presence of chromosomal aberrations.

Galaxamide alleviates cisplatin-induced premature ovarian insufficiency via the PI3K signaling pathway in HeLa tumor-bearing mice

BackgroundIt is challenging to improve the effects of chemotherapy and reduce its adverse impact on the ovaries. Our previous study suggested that the combination of galaxamide could enhance the antitumor effect of cisplatin (CIS) in HeLa cell xenograft mice. However, their potential effects on ovarian tissues remain unknown.MethodsThe Hela tumor-bearing female BALB/c mice model was established and randomly divided into three groups: control group (PBS group), CIS group (0.3 mg/kg CIS group) and galaxamide group (0.3 mg/kg CIS + 3 mg/kg galaxamide-treated group). The serum sex hormones levels, ovarian morphology, functional and molecular characterisation were determined and compared with those of the control group.ResultsThe hormonal effects indicated premature ovarian insufficiency (POI) associated with CIS-induced tumor-bearing mice. CIS induces the apoptosis in primordial and developing follicles and subsequently increases follicular atresia, eventually leading to follicle loss. After cotreatment, galaxamide significantly increased anti-Mullerian hormone (AMH) and follicle-stimulating hormone receptor (FSHR) expression and prevented the CIS-induced PI3K pathway, which triggers follicle activation, apoptosis or atresia.ConclusionThese findings demonstrate that galaxamide could attenuate CIS-induced follicle loss by acting on the PI3K signaling pathway by stimulating AMH and/or FSHR and thus provides promising therapeutic options for patients with cervical cancer.

Cardiometabolic risk factors in women: what's sauce for the goose is not sauce for the gander.

The aim of this review was to discuss cardiometabolic risk factors that affect women. Recent calls to action to address cardiometabolic risk factors specific to women relate to increasing evidence of sex-specific differences in patient-related, drug-related, and socio-demographic factors leading to sub-optimal care of women. Certain aspects of common modifiable cardiovascular risk factors (e.g. smoking, hypertension, dyslipidaemia and diabetes) affect female individuals more adversely. Additionally, there are risk factors or enhancers that particularly affect cardiometabolic health in women [e.g. premature menopause, polycystic ovarian syndrome (PCOS), familial partial lipodystrophy, socio-cultural factors]. Understanding these risk factors may provide insight on how to improve cardiometabolic outcomes in women.

Evaluation of the Effect of Different Inhalation Agents on Ovaries with Hyperthermic Intraperitoneal Chemotherapy: An Experimental Study.

Background and Objectives: Cisplatin is a chemotherapeutic drug that is frequently used with hyperthermic intraperitoneal chemotherapy (HIPEC). Cisplatin-induced gonadotoxicity leads to a depletion of the ovarian reserve, causing premature ovarian insufficiency. This study aimed to investigate the impact of hyperthermia on cisplatin-induced ovarian toxicity and to determine whether sevoflurane or desflurane could be a more appropriate choice of anesthetic for reducing ovarian toxicity in HIPEC procedures. Materials and Methods: A total of 24 New Zealand rabbits were randomly divided into 4 groups as follows: Group H: HIPEC (cisplatin 7 mg/kg), Group HS: HIPEC (cisplatin 7 mg/kg) + 3% sevoflurane (2 h), Group HD: HIPEC (cisplatin 7 mg/kg) + 6% desflurane (2 h), and Group C: Control (Saline). Two catheters were placed in the abdominal cavity, the upper and lower quadrants. The perfusate was heated to 42 °C and given intraperitoneally for 90 min at a rate of 4 mL/min by catheters. Ovarian tissues were collected for Hematoxylin and Eosin staining and immunohistochemical analysis. Results: The primary follicle number was significantly decreased in Group H and HD compared to the C group (p < 0.05). Bax expression was high in Group H, according to all groups (p < 0.0001). Bax expression significantly decreased after sevoflurane, compared to group H (p = 0.012). The bcl-2 expression decreased in all groups compared to the C group. Bcl-2 expression was increased with sevoflurane compared to the H group (p = 0.001). Caspase 3 and p53 expression increased in all groups compared to the C group. p53 expression was decreased with sevoflurane and desflurane compared to the H group (p = 0.002, p = 0.008, respectively). Conclusions: The application of cisplatin with the intraoperative HIPEC method caused ovarian damage. According to our results, sevoflurane anesthesia could be a better option in mitigating cell death I the n ovarian reserve (follicle count) and apoptosis in the HIPEC procedures. We think that our findings should be supported by large series of clinical and experimental studies.

Homozygosity for a stop-gain variant in CCDC201 causes primary ovarian insufficiency

Age at menopause (AOM) has a substantial impact on fertility and disease risk. While many loci with variants that associate with AOM have been identified through genome-wide association studies (GWAS) under an additive model, other genetic models are rarely considered1. Here through GWAS meta-analysis under the recessive model of 174,329 postmenopausal women from Iceland, Denmark, the United Kingdom (UK; UK Biobank) and Norway, we study low-frequency variants with a large effect on AOM. We discovered that women homozygous for the stop-gain variant rs117316434(A) in CCDC201 (p.(Arg162Ter), minor allele frequency ~1%) reached menopause 9 years earlier than other women (P = 1.3 × 10−15). The genotype is present in one in 10,000 northern European women and leads to primary ovarian insufficiency in close to half of them. Consequently, homozygotes have fewer children, and the age at last childbirth is 5 years earlier (P = 3.8 × 10−5). The CCDC201 gene was only found in humans in 2022 and is highly expressed in oocytes. Homozygosity for CCDC201 loss-of-function has a substantial impact on female reproductive health, and homozygotes would benefit from reproductive counseling and treatment for symptoms of early menopause.

Intergenerational Occurrence of Premature Birth and Reproductive Health in Prematurely-Born Women in the Women’s Health Initiative

ObjectiveTo compare reproductive history and postmenopausal health by birth status (preterm vs. full term) in a U.S. longitudinal study of postmenopausal women. Birth status was examined according to region of residence, household, and neighborhood socioeconomic status (SES).MethodsIn the Women’s Health Initiative Observational Study, 2271 women were born prematurely (< 37 weeks). ANOVA and Chi-square determined birth status differences of reproductive history, pregnancy, and postmenopausal health. Odds ratios were calculated using either binary logistic or multinomial logistic regression. SES and U.S. region of residence were examined as potential effect modifiers.ResultsPreterm-born women compared to term-born women had higher risk of delivering a premature infant (aOR 1.68, 95% CI [1.46, 1.93]), higher odds of later-age first pregnancy (aOR 1.27 95% CI [1.02, 1.58]), longer duration to become pregnant (> 1 year to pregnancy) (aOR 1.10 95% CI [1.01, 1.21]), more miscarriages (aOR 1.23 95% CI [1.11, 1.37]), and more pregnancy complications including hypertension (aOR 1.58 95% CI (1.13, 2.21)], preeclampsia (aOR 1.64 95% CI [1.24, 2.16]), and gestational diabetes (aOR 1.68 95% CI [1.11, 2.53]). Preterm-born women had higher odds of menopause before age 50 (aOR 1.09 95% CI [1.05, 1.14]). Post-menopause, they had higher rates of diabetes (p = .01), hypertension (p = .01), hysterectomy (p = .045), and higher Charlson Comorbidity Index scores (p = .01).ConclusionsPreterm-born women had higher reproductive and pregnancy risks which when coupled with early menopause, may indicate a shorter childbearing period than term-born women. Guidelines for integration of preterm history in women’s health care across the life course are needed to identify and manage their higher risk.

Associations of Early Prolonged Secondary Amenorrhea in Women With and Without HIV

Abstract Background The menstrual cycle is a critical indicator of women's health. Early prolonged secondary amenorrhea increases risks for morbidity and mortality. Menstrual cycle research in women with HIV is inconsistent and often lacks an adequate comparison sample. We aimed to determine whether women with HIV have a higher lifetime prevalence of amenorrhea and whether this is independently associated with HIV and/or other biopsychosocial variables. Methods With data from 2 established HIV cohorts, participants assigned female at birth were eligible if aged ≥16 years, not pregnant/lactating, and without anorexia/bulimia nervosa history. Amenorrhea was defined by self-reported history of (1) no menstrual flow for ≥12 months postmenarche not due to pregnancy/lactation, medications, or surgery or (2) early menopause or premature ovarian insufficiency. Multivariable logistic regression models explored biopsychosocial covariates of amenorrhea. Results Overall, 317 women with HIV (median age, 47.5 years [IQR, 39.2–56.4]) and 420 women without HIV (46.2 [32.6–57.2]) were included. Lifetime amenorrhea was significantly more prevalent among women with HIV than women without HIV (24.0% vs 13.3%). In the multivariable analysis, independent covariates of amenorrhea included HIV (adjusted odds ratio, 1.70 [95% CI, 1.10–2.64]), older age (1.01 [1.00–1.04]), White ethnicity (1.92 [1.24–3.03]), substance use history (6.41 [3.75–11.1]), and current food insecurity (2.03 [1.13–3.61]). Conclusions Nearly one-quarter of women with HIV have experienced amenorrhea, and this is associated with modifiable risk factors, including substance use and food insecurity. Care providers should regularly assess women's menstrual health and advocate for actionable sociostructural change to mitigate risks.