Ovarian function recovery in breast cancer patients receiving adjuvant anastrozole treatment: updated results from the phase 3 DATA trial.

PURPOSE: Patients with chemotherapy-induced ovarian function failure (CIOFF) may experience ovarian function recovery (OFR). Earlier, we showed that OFR during treatment with anastrozole impacted the prognosis of hormone receptor-positive (HR+) breast cancer (BC) patients with CIOFF. Here, we present the long-term follow-up results. METHODS: Postmenopausal women with HR+ BC who were 45-57 years of age and received chemotherapy were identified from the phase 3 DATA study (NCT00301457) on the extended use of anastrozole. Eligible patients were categorised into two groups: patients with CIOFF and definitely postmenopausal patients. Patients with CIOFF were monitored for OFR. Disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS) were compared between patients with OFR and patients without OFR using multivariable Cox regression analyses, including OFR as a time-dependent covariate. BC-specific mortality (BCSM) was compared between groups using the Fine and Gray method. RESULTS: This study included 656 patients: 395 patients with CIOFF and 261 definitely postmenopausal patients. OFR occurred in 39 (12%) of 329 patients with CIOFF who were monitored for OFR. The median follow-up time was 13.3 years. Patients with OFR experienced a deterioration in DFS (hazard ratio (HR) = 1.54; 95% confidence interval (CI) 0.85-2.81), DRFS (HR = 1.51; 95% CI 0.73-3.11), OS (HR = 1.64; 95% CI 0.75-3.55), and BCSM (subdistribution HR = 1.98; 95% CI 0.84-4.63) when compared with patients without OFR. CONCLUSION: In patients with CIOFF, OFR during treatment with anastrozole was associated with a deterioration in BC outcomes. These findings underscore the importance of adequate ovarian function suppression in this subgroup of patients.

Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study.

PURPOSE: This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed. PATIENTS AND METHODS: Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison. RESULTS: Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018]. CONCLUSION: Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.

Plasma-derived from human umbilical cord blood restores ovarian function and improves serum reproductive hormones levels in mice with premature ovarian insufficiency (POI) through cytokines and growth factors.

Premature ovarian insufficiency (POI) patients experience a decline in ovarian function and a reduction in serum reproductive hormones, leading to a significant impact on the outcomes of assisted reproductive technology. Despite the absence of an effective clinical treatment to restore fertility in POI patients, recent research has indicated that cord blood plasma (CBP) derived from human umbilical cord blood (hUCB) may offer therapeutic benefits for various degenerative diseases. The primary aim of this study is to explore approaches for enhancing ovarian function and serum reproductive hormones through the administration of CBP in a murine model. Initially, hUCB was utilized to obtain CBP (CBP), which was subsequently analyzed for cytokine and growth factor profiles in comparison to adult blood plasma (ABP) by use of flow cytometry. Subsequently, POI mouse models were established through the induction of 4-vinylcyclohexene diepoxide, followed by the injection of CBP into the tail. At 7, 14, and 21 days posttreatment, mouse ovaries and blood were collected, and their estrus cycle, body weight, and ovarian weights were evaluated using precise electronic balance. Finally, ovarian morphology and follicle number were assessed through HE staining, while serum levels of anti-Müllerian hormone (AMH), estradiol (E2) and follicle-stimulating hormone (FSH) were determined by ELISA. Our study revealed that individuals with CBP exhibited significantly lower concentrations of proinflammatory cytokines, including IL-ß (p < 0.01) and IL-2 (p < 0.05), while displaying elevated levels of anti-inflammatory cytokines and chemokines, such as IL-2, IL-4, IL-6, IL-8, IL-12P70, IL-17A, IP-10, interferon-γ, and tumor necrosis factor-α (p < 0.01). Furthermore, CBP demonstrated remarkably higher levels of growth factors, including transforming growth factor-ß1, vascular endothelial growth factor, and insulin-like growth factor-1 (p < 0.01) than ABP. Notably, our investigation also revealed that CBP restored the content of serum reproductive hormones, such as AMH, E2, and FSH (p < 0.05), and increased the number of primordial and primary follicles (p < 0.01) and decreased the number of luteal and atretic follicles (p < 0.01) in vivo. Our findings suggested that CBP-secreted cytokines and growth factors could be restored POI ovarian function, enhanced serum reproductive hormones and rescued follicular development in vivo. These findings further support the potential of CBP as a promising strategy in clinical applications for POI related infertility.

Cytosine-guanine-guanine repeats of FMR1 gene negatively affect ovarian reserve and response in Chinese women.

RESEARCH QUESTION: Do cytosine-guanine-guanine (CGG) repeats of the FMR1 gene affect ovarian function, ovarian response and assisted reproductive technology (ART) outcomes in Chinese women? DESIGN: A retrospective cohort study of 5869 women who underwent 8932 ART cycles at Women's Hospital, School of Medicine, Zhejiang University between January 2018 and June 2021. Basic hormone level, oocyte yield, embryo quality and the rate of live birth were considered as main outcome measures to evaluate the effects of CGG repeats on ovarian function, ovarian response and ART outcomes. RESULTS: The CGG repeats were negatively related to serum anti-Müllerian hormone (AMH), oestradiol, antral follicle count (AFC) and oocyte yield. A significant association was found between serum AMH, oestradiol and AFC even after age was controlled for. No statistically significant association, however, was found between CGG repeats and embryo quality or live birth rate. Ovarian function mediated the association between CGG repeats and ovarian response. CONCLUSION: Increased CGG repeats on the FMR1 gene were associated with diminished ovarian function and poor ovarian response, and ovarian function played an intermediary role in the relationship between CGG repeats and ovarian response.

Gut microbiota modulation: a narrative review on a novel strategy for prevention and alleviation of ovarian aging.

The global rise in life expectancy corresponds with a delay in childbearing age among women. Ovaries, seen as the chronometers of female physiological aging, demonstrate features of sped up aging, evidenced by the steady decline in both the quality and quantity of ovarian follicles from birth. The multifaceted pathogenesis of ovarian aging has kindled intensive research interest from the biomedical and pharmaceutical sectors. Novel studies underscore the integral roles of gut microbiota in follicular development, lipid metabolism, and hormonal regulation, forging a nexus with ovarian aging. In this review, we outline the role of gut microbiota in ovarian function (follicular development, oocyte maturation, and ovulation), compile and present gut microbiota alterations associated with age-related ovarian aging. We also discuss potential strategies for alleviating ovarian aging from the perspective of gut microbiota, such as fecal microbiota transplantation and probiotics.

Ovarian function in female survivors of high-risk neuroblastoma.

INTRODUCTION: Data on ovarian function in neuroblastoma survivors are limited. We sought to determine the prevalence of ovarian dysfunction in a cohort of high-risk neuroblastoma survivors and compare outcomes among survivors treated with and without autologous stem cell rescue (ASCR) preceded by myeloablative chemotherapy. METHODS: Retrospective review of female survivors of high-risk neuroblastoma ≥5 years from diagnosis, diagnosed between 1982 and 2014, and followed in a tertiary cancer center. Participants were divided into two groups: individuals treated with conventional chemotherapy ± radiation ("non-ASCR") (n = 32) or with chemotherapy ± radiation followed by myeloablative chemotherapy with ASCR ("ASCR") (n = 51). Ovarian dysfunction was defined as follicle-stimulating hormone ≥15 mU/mL, while premature ovarian insufficiency (POI) was defined as persistent ovarian dysfunction requiring hormone replacement therapy. Poisson models were used to determine prevalence ratios of ovarian dysfunction and POI. RESULTS: Among 83 females (median attained age: 19 years [range, 10-36]; median follow-up: 15 years [range, 7-36]), 49 (59%) had ovarian dysfunction, and 34 (41%) developed POI. Survivors treated with ASCR were 3.2-fold more likely to develop ovarian dysfunction (95% CI: 1.8-6.0; p < 0.001) and 4.5-fold more likely to develop POI (95% CI: 1.7-11.7; p = 0.002) when compared with those treated with conventional chemotherapy, after adjusting for attained age. Two participants in the non-ASCR group and six in the ASCR group achieved at least one spontaneous pregnancy. DISCUSSION: Ovarian dysfunction is prevalent in female high-risk neuroblastoma survivors, especially after ASCR. Longitudinal follow-up of larger cohorts is needed to inform counseling about the risk of impaired ovarian function after neuroblastoma therapy.

Ovarian Suppression: Early Menopause, Late Effects.

PURPOSE OF REVIEW: Pre-menopausal women diagnosed with hormone receptor (HR) breast cancer are candidates for prolonged hypoestrogenism to improve cancer outcomes. However, the disease benefit eclipses the toxicities associated with ovarian function suppression (OFS), which are often under-reported. RECENT FINDINGS: Increased risk of mortality from cardiovascular disease, bone disorders, and metabolic disorders is well reported in women with no history of cancer, after surgical oophorectomy or premature ovarian failure. Vasomotor symptoms, urogenital atrophy, weight gain, sexual dysfunction, cognitive decline, and sleep disturbances contribute to the increased non-compliance associated with OFS, especially in younger women. Balancing the toxicities of prolonged OFS with its benefits should be critically analyzed by providers when making recommendations for their patients. Supportive care to manage multi-system toxicities and to counteract the long-term impact on all-cause mortality should be emphasized by every cancer program. Future studies with OFS should incorporate patient outcomes and strategies for symptom management in addition to focusing on improving disease outcomes.

Impact of oxidative stress induced by heavy metals on ovarian function.

As a crucial organ of the female reproductive system, the ovary has both reproductive and endocrine functions. Oxidative stress refers to an increase in intracellular reactive oxygen species (ROS), which play a role in the normal physiological activity of the ovary. However, excessive ROS can cause damage to the ovary. With the advancement of human industrial activities, heavy metal pollution has become increasingly severe. Heavy metals cause oxidative stress through both direct and indirect mechanisms, leading to changes in signal transduction pathways that damage the ovaries. This review aims to outline the adverse effects of oxidative stress on the ovaries triggered by heavy metals such as copper, arsenic, cadmium, mercury, and lead. The detrimental effects of heavy metals on ovaries include follicular atresia and decreased estrogen production in experimental animals, and they also cause premature ovarian insufficiency in women. Additionally, this review discusses the role of antioxidants, provides some treatment methods, summarizes the limitations of current research, and offers perspectives for future research directions.

Socioeconomic development predicts a weaker contraceptive effect of breastfeeding.

The contraceptive effect of breastfeeding remains essential to controlling fertility in many developing regions of the world. The extent to which this negative effect of breastfeeding on ovarian activity is sensitive to ecological conditions, notably maternal energetic status, has remained controversial. We assess the relationship between breastfeeding duration and postpartum amenorrhea (the absence of menstruation following a birth) in 17 World Fertility Surveys and 284 Demographic Health Surveys conducted between 1975 and 2019 in 84 low- and middle-income countries. We then analyze the resumption of menses in women during unsupplemented lactation. We find that a sharp weakening of the breastfeeding-postpartum amenorrhea relationship has globally occurred over the time period analyzed. The slope of the breastfeeding-postpartum amenorrhea relationship is negatively associated with development: higher values of the Human Development Index, urbanization, access to electricity, easier access to water, and education are predictive of a weaker association between breastfeeding and postpartum amenorrhea. Low parity also predicts shorter postpartum amenorrhea. The association between exclusive breastfeeding and maintenance of amenorrhea in the early postpartum period is also found in rapid decline in Asia and in moderate decline in sub-Saharan Africa. These findings indicate that the effect of breastfeeding on ovarian function is partly mediated by external factors that likely include negative maternal energy balance and support the notion that prolonged breastfeeding significantly helps control fertility only under harsh environmental conditions.

Ovarian tissue cryopreservation for fertility preservation before hematopoietic stem cell transplantation in patients with sickle cell disease: safety, ovarian function follow-up, and results of ovarian tissue transplantation.

PURPOSE: To describe the experience of performing ovarian tissue cryopreservation (OTC) before hematopoietic stem cell transplantation (HSCT), among girls/women with severe sickle cell disease (SCD)(SS or S/ß0-thalassemia) who are, besides the usual surgical risk, at risk of SCD-related complications during the fertility preservation procedure for improving their counseling and management. METHODS: This retrospective study included 75 patients (girls/women) with SCD who have had OTC before myeloablative conditioning regimen (MAC) for HSCT. Characteristics of patients and data on OTC, ovarian status follow-up, and results of ovarian tissue transplantation (OTT) were collected in medical records. RESULTS: At OTC, the median (IQR 25-75; range) age of the patients was 9.6 (6.9-14.1; 3.6-28.3) years, 56/75 were prepubertal, and no SCD or surgery-related complications occurred. The median follow-up post-HSCT was > 9 years. At the last follow-up, among prepubertal patients at HSCT, 26/56 were ≥ 15 years old and presented with a premature ovarian insufficiency (POI), except 2, including the patient who had received an OTT to induce puberty. Eight were 13-15 years old and presented for POI. The remaining 22 patients were under 13. Among the 19 patients who were menarche at HSCT, 2 died 6 months post-HSCT and we do not have ovarian function follow-up for the other 2 patients. All the remaining patients (n = 15) had POI. Five patients had OTT. All had a return of ovarian function. One patient gave birth to a healthy baby. CONCLUSION: OTC is a safe fertility preservation technique and could be offered before MAC independent of the patient's age.

Protective effect of bioactive components from Rubi fructus against oxidative damage in human ovarian granulosa cells induced by 2,2-azobis (2-methylpropionamidine) dihydrochloride.

BACKGROUND: Diminished ovarian reserve has a serious impact on female reproduction with an increasing incidence every year. An important cause of this is oxidative stress. Rubi fructus, a traditional medicinal and edible plant, has shown therapeutic effects against gynecological diseases. Vanillic acid, isoquercitrin, kaempferol-3-O-rutinoside, kaempferol-3-O-sophoroside, oleanolic acid, tormentic acid, tiliroside, and ellagic acid are the major bioactive components in R. fructus. However, studies involved in the effectiveness and mechanism of these components in oxidative stress-induced ovarian dysfunction are scarce. RESULTS: In this study, the protective mechanisms of the bioactive components were evaluated in human ovarian granulosa cells. Isoquercitrin was significantly superior to other bioactive components in relieving damage in human ovarian granulosa cells induced by 2,2-azobis (2-methylpropionamidine) dihydrochloride, considering enhanced cell viability, reduced reactive oxygen species accumulation, and improved mitochondrial membrane potential level. Isoquercitrin protected human ovarian granulosa cells from oxidative stress by regulating the enzyme activity of glutathione peroxidase, inhibiting cell apoptosis, improving the expression of genes related to oxidative stress, and ameliorating heme oxygenase 1 protein expression. CONCLUSION: Isoquercitrin, a bioactive component in R. fructus, has a significant protective effect on oxidative damage induced by 2,2-azobis (2-methylpropionamidine) dihydrochloride in human ovarian granulosa cells, providing evidence for its potential application in protecting ovarian function. © 2024 Society of Chemical Industry.

Breast cancer treatment and ovarian function.

The aim of this study was to provide an update on ovarian function and the mechanisms of gonadal damage after exposure to chemotherapy in breast cancer survivors. The alkylating agents are toxic to both primordial and growing follicles. However, anti-metabolite drugs are more likely to destroy preantral and antral follicles. Younger patients are more likely to have a higher ovarian reserve, and therefore, more likely to retain some residual ovarian function after exposure to gonadotoxic regimens. However, there can be significant variability in ovarian reserve among patients of the same age. Furthermore, patients with critically diminished ovarian reserve may continue to menstruate regularly. Therefore age and menstrual status are not reliable indicators of good ovarian reserve and might give a false sense of security and result in an adverse outcome if the patient is consulted without considering more reliable quantitative markers of ovarian reserve (antral follicle count and anti-Müllerian hormone) and fertility preservation is not pursued. In contrast to well-documented ovarian toxicity of older chemotherapy regimens, data for newer taxane-containing protocols have only accumulated in the last decade and data are still very limited regarding the impact of targeted therapies on ovarian function.

Pulmonary benign metastasizing leiomyoma in patients aged 45 years and younger: clinical features and novelty in treatment.

BACKGROUND: Pulmonary benign metastasizing leiomyoma (PBML) is the most common extrauterine spread of uterine leiomyoma, and its biological behavior is traditionally thought to be hormone dependent. Studies on older PBML patients have been previously reported, but limited literature has been published regarding the clinical features and treatment of PBML in young women. METHODS: A total of 65 cases of PBML in women aged 45 years and younger were reviewed, including 56 cases selected from PubMed and 9 cases from our hospital. The clinical characteristics and management of these patients were analyzed. RESULTS: The median age of all the patients at diagnosis was 39.0 years. PBML most commonly presented as bilateral solid lesions (60.9%), with other rare imaging manifestations. The median interval time from a pertinent gynecologic procedure to diagnosis was 6.0 years. A total of 16.7% of patients received careful observation, and all achieved stable status in a median follow-up time of 18.0 months. A total of 71.4% of patients were administered anti-estrogen therapies, including surgical castration (33.3%), gonadotropin-releasing hormone analog (23.8%) and anti-estrogen drugs (14.3%). Eight of 42 patients underwent surgical resection of metastatic lesions. Patients who underwent curative surgery for the removal of pulmonary lesions combined with adjuvant anti-estrogen therapies had favorable outcomes compared with those who only underwent surgical resection. The disease control rates of surgical castration, gonadotropin-releasing hormone analog, and anti-estrogen drugs were 85.7%, 90.0%, and 50.0%, respectively. For two patients, sirolimus (rapamycin) achieved successful relief of symptoms and control of pulmonary lesions without lowering hormone levels and causing estrogen deficiency symptoms. CONCLUSIONS: In the absence of standard treatment guidelines for PBML, maintaining a low-estrogen environment using different kinds of antiestrogen therapies has been the mainstream strategy and has satisfying curative effects. A wait-and-see strategy might be an option, but therapeutic approaches must be contemplated when complications or symptoms progress. For PBML in young women, the negative effect on ovarian function of anti-estrogen treatment, especially surgical castration, should be considered. Sirolimus might be a new treatment option for young PBML patients, especially for those who want to preserve ovarian function.

A composite menstrual cycle of captive orangutans, with associated hormonal and behavioral variability.

Knowledge of species-typical reproductive endocrinology profiles is crucial for testing hypotheses pertaining to the evolutionary history, reproductive parameters, and life history of a species, and for managing the well-being of individual animals in human care. Large-scale empirical measurements of ovarian hormones, however, are rare for most primate species, including orangutans. In this study, we used enzyme immunoassays (EIA) to quantify estrogen (estrone conjugates; E1 C) and progesterone (pregnanediol-3-glucuronide; PdG) levels for 98 cycles in 7 cycling zoo-housed female orangutans (10-43 years old). We use a subset of these cycles (N = 44) to create the first composite menstrual cycle for orangutans, which serves as a valuable baseline for future comparative analyses and veterinary considerations. Similar to previous studies, we determined the mean ovarian cycle length of orangutans to be 29.7 days (N = 98 cycles), although we illustrate evidence of both intra- and interindividual variation in ovarian steroid production. Given that this study took place in captivity, we consider how energetic and psychosocial aspects of the zoo environment, such as greater food availability and potential stress, may affect the reproductive physiology and sexual behavior of these females. Furthermore, we discuss the role that age and genetic background may play in producing variability. Finally, we test whether ovarian hormone levels correlate with the reproductive behaviors of these female orangutans using associated behavioral data. Our results suggest that matings are more common during the periovulatory period than outside of it, but do not support a consistent link between hormonal indices of fecundability and mating behaviors in these individuals.

Transcriptome identification and characterization of long non-coding RNAs in the ovary of hens at four stages.

Long non-coding RNAs (lncRNAs) play important roles in transcriptional and post-transcriptional regulation. LncRNAs, which are defined as non-coding RNAs more than 200 bp in length, are involved in key biological processes, such as cell proliferation and differentiation, epigenetic regulation, and gene transcriptional translation. Recent studies have shown that lncRNAs also play major regulatory roles in the reproduction of mammals. However, knowledge of the roles of lncRNAs in the chicken ovary lacking. In this study, we performed RNA-seq analyses of ovarian tissue from Hy-Line brown laying hens at four physiological stages [15, 20, 30, and 68 weeks of age (W)]. We identified 657 lncRNA transcripts that were differentially expressed during ovarian development, the number of down-regulated lncRNAs was higher than the number of up-regulated lncRNAs during development. We predicted the cis and trans target genes of the DE lncRNAs and constructed a lncRNA-mRNA interaction network, which indicated that the DE genes (DEGs) and the target genes of the DE lncRNAs are mainly involved in signaling pathways associated with ovarian development, including oocyte meiosis, calcium signaling pathways, ECM-receptor interactions, and ribosome and focal adhesion. Overall, we found that twelve lncRNAs were strongly involved in ovarian development: LNC_013443, LNC_001029, LNC_005713, LNC_016762, ENSGALT00000101857, LNC_003913, LNC_013692, LNC_012219, LNC_004140, ENSGALT00000096941, LNC_009356, and ENSGALT00000098716. In summary, our study utilized RNA-seq analysis of hen ovaries to explore key lncRNAs involved in ovarian development and function. Furthermore, the comprehensive analysis identified the target genes of these lncRNAs providing a better understanding of the mechanisms underlying ovarian development in hens and a theoretical basis for further research.

In utero bisphenol A exposure disturbs germ cell cyst breakdown through the PI3k/Akt signaling pathway and BDNF expression.

PURPOSE: To determine the influence of the environmental endocrine disruptor bisphenol A (BPA) on germ cell cyst breakdown and explore the possible mechanisms regulating this activity. METHODS: BPA (2 µg/kg/d or 20 µg/kg/d) or tocopherol-stripped corn oil (vehicle control) was administered to pregnant mice by gavage at gestational day 11, and the offspring (prenatally treated mice) were sacrificed and ovariectomized at postnatal day (PND) 4 and PND22. Ovarian morphology was documented in the first filial (F1) generation female offspring, and the follicles were analyzed and classified morphologically on PND 4. To discover differentially expressed genes and associated target pathways, we used RNA-seq, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Ontology (GO) analysis. The mRNA expression of key steroid hormone synthesis-related genes was evaluated by Q-PCR in forskolin-induced KGN cells. Western blotting (WB) and qRTPCR were used to determine the protein and gene expression levels of brain-derived neurotrophic factor (BDNF). RESULTS: BPA, a typical endocrine disrupting chemical (EDC), decreased the expression of the key steroid hormone synthesis-related genes P450scc and aromatase, while the expression of Star increased significantly and caused no significant difference in the expression of Cyp17a1 or HSD3ß in forskolin-induced KGN cells. Moreover, we confirmed that in utero exposure to environmentally relevant concentrations of BPA (2 µg/kg/d and 20 µg/kg/d) could significantly disrupt germ cell cyst breakdown, leading to the generation of fewer primordial follicles than in the control group. The factors mediating the inhibitory effects included the PI3K-Akt signaling pathway and a significant downregulation of BDNF. CONCLUSIONS: These findings indicate that in utero exposure to BPA at low doses, which are lower than recommended as 'safe' dosages, may influence the formation of primordial follicles by inhibiting the expression of steroid hormone synthesis-related genes and partly by regulating the BDNF-mediated PI3K/Akt pathway.

Chromosomal polymorphisms and susceptibility to menstrual disorders: a retrospective analysis of 24,578 women.

PURPOSE: To evaluate the association between the polymorphic variants of chromosomes and menstrual disorders. METHODS: The data from our previous retrospective, single-center cohort study were re-analyzed. Women with regular menstruation were included as controls. Women with menstrual cycle abnormalities were subgrouped according to reproductive causes. The frequency of chromosomal polymorphisms was compared between groups. Regression analysis was used to adjust for potential confounding variables. RESULT: A total of 24,578 women composed of 8062 women with regular cycles as the control group and 16,516 women as the menstrual cycle irregularity group were included. When compared with the control group, the incidence of chromosomal polymorphisms in the total menstrual cycle irregularity group, Polycystic ovary syndrome group, and Primary ovarian insufficiency group were significantly higher (4.49% versus 5.34%, P = 0.004, 4.49% versus 5.35%, P = 0.018 and 4.49% versus 5.94%, P = 0.002, respectively). The incidences of inv(9) in the Primary ovarian insufficiency group were significantly higher than that in the control individuals (1.0% versus 1.6%, P = 0.024). Logistic regression analysis showed an effect of chromosomal polymorphisms on menstrual cycle irregularity (OR: 1.62, 95% CI: 1.234-2.187, P = 0.007; adjusted OR: 1.46, 95% CI: 1.153-1.819, P < 0.001). The result demonstrated an effect of chromosomal polymorphisms on the Primary ovarian insufficiency group (OR: 2.52, 95% CI: 1.307-5.177, P < 0.001; adjusted OR: 2.61, 95% CI: 1.371-4.605, P < 0.001). CONCLUSION: The study suggests chromosomal polymorphisms adversely affect female menstrual cycle irregularity.

The Intergeneration Long-Lasting Consequences of Pre-Conceptional Exposure to Sofosbuvir on the Ovarian Tissues of F1 Offspring: Experimental Study on Rats.

Sofosbuvir (SOF), a nucleos(t)ide polymerase inhibitor, has been used during the past decade for mass treatment of viral hepatitis C in endemic countries like Egypt, increasing the exposure of women at childbearing age to SOF. This study investigated the long-lasting consequences of the pre-conceptional exposure of young female rats to SOF on the ovarian tissues of F1 offspring and explored the possible molecular mechanisms of these intergenerational effects at various levels. The study was conducted on young female rats that were divided into control group and SOF-exposed group at a dose of 4 mg/kg/day for three months. After that, pregnancy was induced in both groups by mating with healthy male rats. After delivery, the female neonates were followed for 4 months, and the ovarian tissues were collected to assess the studied parameters. Pre-conceptional exposure to SOF affected the ovarian functions of F1 offspring through modulation of estrogen receptors, ovarian Kiss1 and its receptor, increased lipid peroxidation marker, DNA oxidation marker, and redox-sensitive nuclear factor kappa B, and decreased nuclear erythroid-2-related factor 2, mitochondrial function, and biogenesis. SOF affected the ovarian function of the F1 offspring by inducing oxidative stress and inflammation, leading to the modulation of mitochondrial functions and biogenesis.

Measurement of ovarian reserve in infertile versus fertile women: A case control study in Edo State, Nigeria.

The reproductive potential in a woman is age related. Nevertheless, the female reproductive system undergoes ovarian follicular development, resulting in ovulation of matured ovum for fertilization. Consequently, female reproductive aging parallels the depletion of the store of follicles until menopause is attained. This is the essential reason for evaluating ovarian reserve in women of reproductive age for infertility screening. The objective of the present study is to compare the serum FSH, LH, estradiol and progesterone levels in infertile women with fertile controls. The study was designed as a case control descriptive study conducted in Benin City Edo State, Nigeria. Data were obtained through Questionnaire interview, while ELISA technique was used in the hormone analysis. Seventy-one women participated, of which 42 of them were infertile; and 29 age-matched fertile women (as controls). Secondary infertility was higher (64.3%) with 35% of them married between 3 and 5 years. The infertile patients had a significantly higher BMI than the controls (p <0.001). There was a significant difference in the serum levels of FSH and LH of the infertile women compared to the controls (p-value =0.001 and <0.001) respectively. Similarly, day 3 and day 21 serum progesterone levels of controls were significantly higher than those of the infertile women (p-value = 0.001 and 0.001) respectively. Though mean serum estradiol levels were higher in controls than the infertile women it was however not statistically significant (P=0.191). Sexually transmitted infections / pelvic inflammatory disease was identified to be treated in 52% of the infertile women. In conclusion, measurement of serum FSH, LH, Estradiol, Days 3 and 21 Progesterone collectively or FSH / LH ratio could be useful as markers for the assessment of ovarian reserve in women with infertility.

Ovarian Function Suppression: A Deeper Consideration of the Role in Early Breast Cancer and its Potential Impact on Patient Outcomes: A Consensus Statement from an International Expert Panel.

It has been suggested that the benefit of adjuvant chemotherapy (CT) in premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) early breast cancer may be related, at least in part, to CT-induced ovarian function suppression (OFS) in this subgroup of patients. Although this hypothesis has not been directly tested in large randomized clinical trials, the observations from prospective studies have been remarkably consistent in showing a late benefit of CT among the subgroup of patients who benefit (ie, women who were close to menopause). The hypothesis has important clinical implications, as it may be possible to spare the associated adverse effects of adjuvant CT in a select group of women with early breast cancer, in favor of optimizing OFS and endocrine therapy (ET), without compromising clinical outcomes. Such an approach has the added benefit of preserving the key quality of life outcomes in premenopausal women, particularly by preventing the irreversible loss of ovarian function that may result from CT use. For this reason, we convened an international panel of clinical experts in breast cancer treatment to discuss the key aspects of the available data in this area, as well as the potential clinical implications for patients. This article summarizes the results of these discussions and presents the consensus opinion of the panel regarding optimizing the use of OFS for premenopausal women with HR+, HER2- early breast cancer.