Hormone Replacement Research Articles

Effects of Hormonal Replacement Therapy and Mindfulness-Based Stress Reduction on Climacteric Symptoms Following Risk-Reducing Salpingo-Oophorectomy.

Breast Cancer Associated Susceptibility Proteins Type 1/2 (BRCA1/2) promote cellular functioning by modulating NRF2-mediated antioxidant signaling. Redox failure in women with BRCA1/2 insufficiency increases the risk for breast/ovarian/uterine cancers. Risk-reducing salpingo-oophorectomy (RRSO) is a prophylactic surgery of the reproductive organs, which is frequently conducted by the age of 40 to lower the occurrence of cancer in women with BRCA1/2 mutations. However, abrupt estrogen decline following RRSO causes ovarian failure, which implicates various cellular physiological processes, resulting in the increased release of free radicals and subsequent severe onset of menopausal symptoms. Comfort measures (e.g., hormonal replacement therapy (HRT) and mindfulness-based stress reduction (MBSR)) may improve chronological menopause-related quality of life, but their specific effects are not clear in women with gene mutations. Aiming to fill the gap, this study used path analysis to examine the effects of HRT and MBSR on menopausal symptoms among RRSO patients (N = 199, mean age = 50.5 ± 6.7 years). HRT directly alleviated the levels of urogenital symptoms (β = -0.195, p = 0.005), which mediated its indirect significant effects on the somatic-vegetative and psychological symptoms of menopause (β = -0.046, -0.067; both p values = 0.004, respectively), especially in BRCA2 carriers and in women who were currently physically active, premenopausal at the time of RRSO, had a high BMI, and had no history of breast cancer. It increased the severity of urogenital symptoms in women with a history of cancer. MBSR, on the other hand, was associated with indirect increases in the intensity of the somatic-vegetative and psychological symptoms of menopause (β = 0.108, 0.029; p = 0.003, 0.033, respectively). It exerted positive direct effects on different menopausal symptoms in multigroup analysis. The results suggest that young women undergoing recent RRSO may benefit from HRT at an individual level, while their need for extensive measures to optimize their psychological wellbeing is ongoing. The adverse effects of MBSR, which are captured in the present study, imply that MBSR may interfere with redox sensitivity associated with estradiol fluctuations in BRCA1/2 carriers. Investigations are needed to test this hypothesis and elaborate on the underlying mechanisms in these women.

Aging promotes accumulation of senescent and multiciliated cells in human endometrial epithelium.

What changes occur in the endometrium during aging, and do they impact fertility? Both the transcriptome and cellular composition of endometrial samples from women of advanced maternal age (AMA) are significantly different from that of samples from young women, suggesting specific changes in epithelial cells that may affect endometrial receptivity. Aging is associated with the accumulation of senescent cells in aging tissues. Reproductive aging is mostly attributed to the decline in ovarian reserve and oocyte quality, whereas the endometrium is a unique complex tissue that is monthly renewed under hormonal regulation. Several clinical studies have reported lower implantation and pregnancy rates in oocyte recipients of AMA during IVF. Molecular studies have indicated the presence of specific mutations within the epithelial cells of AMA endometrium, along with altered gene expression of bulk endometrial tissue. Endometrial transcriptome profiling was performed for 44 women undergoing HRT during the assessment of endometrial receptivity before IVF. Patients younger than 28 years were considered as the young maternal age (YMA) group (age 23-27 years) and women older than 45 years were considered as the AMA group (age 47-50 years). Endometrial biopsies were obtained on Day 5 of progesterone treatment and RNA was extracted. All endometrial samples were evaluated as being receptive based on the expression of 68 common endometrial receptivity markers. Endometrial samples from another 24 women classified into four age groups (YMA, intermediate age group 1 (IMA1, age 29-35), intermediate age group 2 (IMA2, age 36-44), and AMA) were obtained in the mid-secretory stage of a natural cycle (NC) and used for validation studies across the reproductive lifespan. A total of 24 HRT samples (12 YMA and 12 AMA) were subject to RNA sequencing (RNA-seq) and differential gene expression analysis, 20 samples (10 YMA and 10 AMA) were used for qPCR validation, and 24 NC samples (6 YMA, 6 IMA1, 6 IMA2 and 6AMA) were used for RNA-seq validation of AMA genes across the woman's reproductive lifespan. Immunohistochemistry (IHC) was used to confirm some expression changes at the protein level. Computational deconvolution using six endometrial cell type-specific transcriptomic profiles was conducted to compare the cellular composition between the groups. Comparisons between YMA and AMA samples identified a lower proportion of receptive endometria in the AMA group (P = 0.007). Gene expression profiling identified 491 differentially expressed age-sensitive genes (P adj < 0.05) that revealed the effects of age on endometrial epithelial growth and receptivity, likely contributing to decreased reproductive performance. Our results indicate that changes in the expression of the cellular senescence marker p16INK4a and genes associated with metabolism, inflammation, and hormone response are involved in endometrial aging. Importantly, we demonstrate that the proportion of multi-ciliated cells, as discovered based on RNA-seq data deconvolution and tissue IHC results, is affected by endometrial aging, and propose a putative onset of age-related changes. Furthermore, we propose that aging has an impact on the transcriptomic profile of endometrial tissue in the context of endometrial receptivity. The raw sequencing data reported in this article are deposited at the Gene Expression Omnibus under accession code GSE236128. This retrospective study identified changes in the endometrium of patients undergoing hormonal replacement and validated these changes using samples obtained during a NC. However, future studies must clarify the importance of these findings on the clinical outcomes of assisted reproduction. The findings reported in this study have important implications for devising future strategies aimed at improving fertility management in women of advanced reproductive age. This research was funded by the Estonian Research Council (grant no. PRG1076), Horizon 2020 innovation grant (ERIN, grant no. EU952516), Enterprise Estonia (grant no. EU48695), MSCA-RISE-2020 project TRENDO (grant no. 101008193), EU 874867 project HUTER, the Horizon Europe NESTOR grant (grant no. 101120075) of the European Commission, the EVA specialty program (grant no. KP111513) of the Maastricht University Medical Center (MUMC+), MICIU/AEI/10.13039/501100011033 and FEDER, EU projects Endo-Map (grant no. PID2021-12728OB-100), ROSY (grant no. CNS2022-135999), and the National Science Fund of Bulgaria (grant no. KII-06 H31/2). The authors declare no competing interests.

Immunotherapy is a new opportunity for managing patients with “thin” endometrium in cycles of transfer of thawed embryos

The trend of recent decades has been the search for therapeutic effects on the so-called “thin” endometrium. However, to date there is no optimal management scheme for patients with “thin” endometrium in assisted reproductive technology programs. Aim: to evaluate the effectiveness of using recombinant IL-2 before cryotransfer in women of late reproductive age with “thin” endometrium and repeated implantation failure after transfer of good quality embryos. The study included 63 patients of late reproductive age with “thin” endometrium. The first group consisted of 25 patients of late reproductive age with a history of unsuccessful in vitro fertilization programs with good quality embryos. Cryotransfer to the patients of the first group was carried out in a modified natural cycle. The second group included 38 women of late reproductive age with a history of unsuccessful in vitro fertilization programs with good quality embryos. Cryotransfer for women of the second group was carried out in a cycle with hormone replacement therapy. Recombinant IL-2 in the cycle before cryotransfer were prescribed to all women. In both groups, implantation, clinical pregnancy, and live birth rates following administration of recombinant IL-2 were valuable. In both groups, the implantation rate, clinical pregnancy rate and live birth rate were assessed after administration of recombinant IL-2. Statistical data processing was performed using application software package Statistica 6.0 (StatSoft, Ink. 1994-2001), adapted for biomedical research. p 0.05 was considered significant. After recombinant IL-2 treatment of patients with infertility and thin endometrium, endometrial thickness increases statistically significantly in the first two menstrual cycles after treatment, so transfer of thawed embryos should be planned in the first two menstrual cycles after immunotherapy. In order to increase the thickness of the endometrium during cryotransfer in a modified natural cycle, as well as in a cycle with replacement hormone therapy, recombinant IL-2 can be used in women with “thin” endometrium with repeated unsuccessful implantation attempts when transferring good quality embryos. Cryotransfer should be performed in the first two menstrual cycles after immunotherapy.

Evaluation of the Potential Beneficial Effects of Ferula communis L. Extract Supplementation in Postmenopausal Discomfort.

Peri-menopausal discomfort can have a detrimental effect on the physical health of women due to physiological and behavioral changes. Estrogen and progesterone-based hormone therapy can alleviate menopausal symptoms, but estrogen supplementation may have negative health effects. The effectiveness of hormone replacement therapy using natural compounds for peri-menopausal disorders is still uncertain. Evidence from in vivo experiments indicates that Ferula L. extract in ovariectomized rats leads to better sexual behavior. The effect seems to be linked to the phytoestrogenic properties of ferutinin, the primary bioactive compound in the extract. The purpose of this study was to assess the clinical impact of Ferula communis L. extract (titrated at 20% ferutinin, and given at doses of 100 mg/die for 90 days) on the quality of life of 64 menopausal women. The clinical trial was randomized, double-blind, and placebo controlled. Our data showed that Ferula communis L. extract reduced by 67 + 9% all symptoms associated to postmenopausal discomfort and enhanced significantly sexual behavior. In addition, the supplement led to a significant improvement of BMI and oxidative stress decrease in the women who received it, while also keeping platelet aggregation within normal levels. Overall, these results could point to the potential use of supplementation with Ferula communis L. extract to revert or mitigate menopause dysfunction.

Re-evaluating the Relationship between Cosmetic Products and Cancer: An Investigative Review of Paradigms

Abstract: Cosmetics are items that are used to glorify or change facial looks and appearance as well as provide fragrance to the body. Their main aim is to cleanse, beautify, facilitate attractiveness, and change physical looks. Women use many different beauty products, such as skin care, hair, perfume, oral hygiene, and nail care items, which may include harmful substances that are threatening to their health. The controversy around cosmetics and beauty products promoting cancer threat has grown over the previous few years. According to data from the European Cancer Registries, postmenopausal and very young women are now seeing an increase in the occurrence of breast cancer, which is the more frequent form of cancer in women. Genetic predisposition, long-term hormone replacement treatment, and various environmental variables, including air pollution, agrochemicals, alcohol, and specific consumer goods like cosmetic additives, are some of the causes of breast cancer. Additionally, the USFDA made all adverse event reports, including those involving concerns about cosmetics, publicly accessible via the Adverse Event Reporting System (CAERS) of the Centre for Food Safety and Applied Nutrition in 2016. In this period of modernization, CAERS is of limited use since there is a lack of different supporting data, such as demographic information, medical history, or linked product usage, and because the existing data is vulnerable to severe reporting bias. Despite the system's potential to protect the public's health, the database's future usefulness will depend on a wide range of reporting participants, more thorough reporting, and concurrent investments in regulatory science and enhanced molecular techniques.

Injectable Biomimetic Hydrogel Constructs for Cell-Based Menopausal Hormone Therapy with Reduced Breast Cancer Potential.

Hormone replacement therapy (HRT) has been a primary method in menopausal women and patients with ablated ovaries, but safety has been a concern. Cell-based HRT has emerged as an alternative approach without side effects causing pharmaceutical HRT via 3-dimensionally engineered constructs layering ovarian hormone-producing cells. In this study, we applied micro-sized ovarian cell-laden hydrogel beads as an approach to cell-based HRT using a minimally invasive method in the menopausal rat model. Here, we constructed GC/TC-laden microbeads (GTBs; GC, granulosa cell; TC, theca cell) that allow crosstalk between endocrine cells, encapsulating multiple beads for the figuration of the original ovary. We assessed the ovarian hormone production function of GTB through invitro culture for 90 days. We applied it to a menopausal rat model and confirmed that GTB-injected rats restored their endocrine function, leading to the regeneration of the thinned endometrium and the maintenance of regular estrous cycles in some individuals. Additionally, it was observed to alleviate menopausal symptoms, including body weight gain and osteoporosis. Notably, the GTB-injected rats did not show mammary gland hyperplasia observed in the pharmaceutical HRT groups and exhibited fewer p53- and KI67-positive and an increase in phosphatase and tensin homolog-positive mammary gland epithelial cells compared to pharmaceutical hormone-treated rats. These results suggest that GTB-based HRT could present a lower risk of breast cancer compared to conventional pharmaceutical-HRT use. Our study highlights the potential of cell-based HRT using an injectable artificial ovary, offering a safer alternative for women requiring HRT.

Exploring the Effect of Thyroid Hormone on Serum Lipoprotein (a) Levels in Patients With Thyroid Hormone Dysfunction: A Systematic Review.

Genetic variations among people mainly determine the blood levels of lipoprotein (a) (Lp(a)), and it is relatively stable throughout one's lifetime. Nevertheless, there could still be other factors that control the Lp(a) level. Thyroid hormones are known to influence the serum lipid level by regulating the expression ofkeyenzymes that are involved in lipid metabolism. Both hypo and hyperthyroidism are associatedwith changes in lipid levels. Even though thyroid hormone abnormalities have been shownto alter traditional lipid parameters like low-density lipoprotein (LDL-C), its influence onLp(a) has not been established. This review aims to identify the relationship between Lp(a) and thyroid hormones by reviewing data from correlative studies and observing treatment-related Lp(a) level changes in thyroid disorders from interventional studies. We searched MEDLINE, Cochrane, and Google Scholar databases with predefined search criteria and search strategies for paper identification. Individual reviewers reviewed identified papers for selection.Finalized papers were reviewed forLp(a) levels and their responses to treatment in patients with thyroid disorders to establish the relationship betweenLp(a) and thyroid hormone.We concluded that the data were limited and sometimes contradicted one another to establish a clear relationship betweenLp(a) and thyroid hormones.Even though correlative studies data showed strong indications that overt-hypothyroidism was associated with high Lp(a) levels, thyroid hormone replacement studies did not show any significant changes inLp(a) levels compared to pre-treatment in patients with both overt-hypothyroidism and subclinical hypothyroidism. More clinical trials focusing on Lp(a) with longer periods of treatment and follow-up in thyroid patients are needed to establish the relationship between the two. The possibility of dose-related Lp(a) responses to thyroid hormone treatment should also be explored.

Hypothyroidism in Older Adults: A Concise Review of the Recent Literature

Abstract Introduction Hypothyroidism (HypoT) is a common condition whose prevalence varies according to regional and ethnic factors, dietary iodine, gender, and age. The symptoms of HypoT are generally nonspecific, with considerable overlap with other conditions. These symptoms are not useful for diagnosing HypoT, and a thyroid function test is required for a final diagnosis. Materials and methods We aimed to provide an overview of the recent global literature on HypoT in older adults. A narrative, nonsystematic review of the international literature from a single major medical online database (PubMed) for the past 5 years was performed. The relevant literature was narrated in a concise thematic account. Results Most studies and expert opinions reiterated the benefit of replacement therapy in younger and middle-aged individuals. A good volume of literature also considered the interplay between thyroid hormones and (1) cardiovascular function and risk factors, (2) cognitive function, (3) mental health, and (4) quality of life. Most workers are cognizant of the important difference in normal ranges of thyroid-stimulating hormone (TSH) and the consequent TSH targets in older adults compared to younger age groups. Extra care is recommended for the initiation and titration of thyroid hormone replacement therapy to avoid cardiovascular and skeletal adverse effects of relative overtreatment. Conclusion While clinical benefit is evident in patients under age 65 with overt and subclinical HypoT who are treated with levothyroxine, treatment may be harmful in older adults with subclinical HypoT. The 97th percentile of TSH distribution is 7.5 mIU/L for patients over age 80. Hence, TSH goals should be individualized in older adults to achieve any possible benefit and avoid unnecessary harm.

Cross-sex hormonal replacement: Some effects over mitochondria

Transgender is a term for people whose gender identity or expression differs from their natal sex. These individuals often seek cross-hormonal therapy to simulate the individual´s desired gender. However, the use of estrogens and testosterone has side effects such as a higher propensity to cancer, weight changes and cardiovascular diseases. Testosterone has also been linked with hypertension. Still, little is known about the outcomes and prevalence of metabolic perturbations in the trans community. Here we aim to analyze if cross-administering sexual hormones affects heart mitochondrial function. Mitochondria produces the ATP needed for heart function. In fact, different studies show that mitochondrial dysfunction precedes cardiac damage. In this work we used either female rats castrated and injected with testosterone or male rats castrated and injected with estrogens for 4 months. We performed an electrocardiogram, and then we isolated heart mitochondria to measure the rate of oxygen consumption, calcium fluxes, membrane potential, superoxide dismutase activity, lipoperoxidation and cytokines. We detected wide modifications in all parameters associated to cross-hormonal administration.

Exploring Resveratrol Intervention in Managing Menopausal Symptoms: A Comprehensive Systematic Review of Clinical Trials

Introduction: Menopause, a significant event in a woman's reproductive lifespan, entails hormonal changes and a range of symptoms affecting various bodily systems. Conventional treatments like hormone replacement therapy (HRT) have limitations and associated risks, prompting interest in alternative therapies such as resveratrol. Materials/Methods: The literature search was conducted in six databases. The outcome of interest measures the mean changes in bone mineral density (BMD), Quality of Life (QoL), bone biomarkers, menopause symptoms, and cognitive and mood functions pre- and post-interventions. Resveratrol was administered in various forms and doses, including trans-resveratrol 75 mg twice or once daily, 250/500/1000 mg resveratrol tablets, and a combination of fermented soy containing 10 mg equol and 25 mg resveratrol. Quality appraisal was done using the Cochrane Risk of Bias Tool 2. Results: Resveratrol supplementation in post-menopausal women, involving 745 participants across various studies, has shown remarkable health benefits. These include improved cerebral vasoreactivity (CVR) to hypercapnia, a 10% decrease in overall pain, and enhanced quality of life. Additionally, resveratrol boosts flow-mediated dilation (FMD) by 23% and increases serum sex hormone-binding globulin (SHBG) concentrations by 10%, benefiting bone mineral density (BMD). Over the long term, it leads to a significant 35% increase in FMD and a substantial 33% enhancement in overall cognitive performance, highlighting its diverse benefits. Conclusion: For women in the post-menopausal stage, resveratrol supplementation shows potential for improving cardiovascular health, relieving pain, enhancing quality of life, supporting bone health, boosting cognitive function, and promoting overall mental well-being.

Hormone Replacement Therapy (HRT) Shortages for Treating Menopause: What Can Clinicians Do to Relieve Symptoms and Concerns?

Hormone Replacement Therapy (HRT) Shortages for Treating Menopause: What Can Clinicians Do to Relieve Symptoms and Concerns?

Postmenopausal Hormone Therapy Was Associated With Later Age of Onset Among Glaucoma Cases.

Hormonal therapy (HT) has been suggested to lower the risk of developing glaucoma. Our goal was to investigate the association between HT use and the onset of glaucoma diagnosis in postmenopausal women. This retrospective case-only study included female veterans with open-angle glaucoma from VA records between 2000 to 2019. Propensity score matching was used to match HT (n = 1926) users to untreated (n = 1026) women on multiple covariates (e.g., age of menopause, BMI, blood pressure, antihypertensive medications, and a co-morbidity index). A simple linear regression was used to evaluate the impact of HT duration on the age of glaucoma diagnosis, and multivariate linear regression analysis was used to determine which factors contributed to the age at diagnosis of glaucoma. We found a linear relationship between the age at diagnosis of glaucoma and menopause in women with (r = 0.54) and without HT (r = 0.57) use. HT users tended to have a later diagnosis of glaucoma. Our multivariate analysis found that 0-2 years, 2-5 years, and >5 years of HT use were associated with a 2.20 [confidence interval (CI), 1.64, 2.76], 3.74 [CI, 3.02, 4.46], and 4.51 [CI, 3.84, 5.18] years later diagnosis of glaucoma. An interaction (-0.009 [-0.015, -0.003]) was observed between HT duration and age of menopause diagnosis, with the impact of HT decreasing for later menopause ages. Longer duration of HT use was associated with a later diagnosis of glaucoma in postmenopausal women in this case-only analysis. The impact of HT may be modulated by menopausal age, although further study is needed. The findings support a protective role of estrogen in glaucoma pathogenesis.

A comprehensive study of adverse effects of chemotherapy on female breast cancer patients in NORI Cancer Hospital, Islamabad in a developing country.

Breast cancer is one of the top three malignancies worldwide. While radiotherapy, hormone replacement therapys, and chemotherapy are treatments, chemotherapy causes adverse effects that hinder daily life activities. To assess the prevalence, severity, and association of symptomatic toxicities in female breast cancer patients affecting various organ systems post systemic chemotherapy (adjuvant and neoadjuvant), and their impact on daily activities. Additionally, to determine the severity of adverse effects in specific age groups and their association with family history and disease stage. An observational study was conducted on 253 female breast cancer patients receiving chemotherapy at NORI Cancer Hospital from May to October 2023. Data collection tools included the NCI-PRO-CTCAE standardized questionnaire and patient medical records. Analysis was performed using descriptive statistics, T-tests, and Chi-square tests. Among the 253 patients, 41.4% were aged 41-50. Significant weight changes (p = 0.034) were observed with more than three chemotherapy cycles. Notable associations included increased chemotherapy cycles with gastrointestinal (mouth/throat sores p = 0.031, vomiting p = 0.021), respiratory (cough p = 0.04), cardiovascular (arm/leg swelling p = 0.007, palpitations p = 0.052), integumentary (hair loss p = 0.000, skin dryness p = 0.054), and musculoskeletal (fatigue p = 0.002) adverse effects. Positive family history and the 18-30 age group also showed significant associations with adverse effect severity. Disease stage significantly influenced the nervous system (stage 2 p = 0.007, stage 3 p = 0.01). The severity of adverse effects varies among age groups, depending on disease stage, genetics, and treatment duration. These patient-reported outcomes highlight the need for better management strategies considering prognostic factors and treatment adverse effects.

The Potential Role of Female Sex Hormones in Patients With Inflammatory Bowel Disease: A 2-Sample Mendelian Randomization Study.

An association between female sex hormones and inflammatory bowel disease (IBD) has been reported in epidemiological studies. However, a solid causal relationship has not been established. Therefore, we performed a 2-sample Mendelian randomization (MR) study to explore the causal association between genetically predicted female sex hormone exposure, especially estrogen, and IBD. Genetic variants for female sex hormone exposure (ovulatory function, reproductive function, oral contraceptive pills, and hormone replacement therapy) were obtained from genome-wide association studies. Summary statistics for IBD were derived from the International Inflammatory Bowel Disease Genetics Consortium. We applied inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods in this MR study. Heterogeneity, horizontal pleiotropy, and sensitivity analyses were conducted to confirm the accuracy and robustness of our results. Our study found that genetically predicted age at menarche was associated with an increased risk of Crohn's disease (odds ratio [OR] IVW 1.235, 95% confidence interval [CI] 1.028-1.484, P = 0.024), genetically predicted age of the last used hormone replacement therapy was associated with an increased risk of ulcerative colitis (OR WM 1.636, 95% CI 1.011-2.648, P = 0.045), and genetically predicted number of live births was related to a decreased risk of Crohn's disease (OR IVW 0.583, 95% CI 0.373-0.912, P = 0.018). This study provided evidence for a link between female sex hormone exposure, especially estrogen, and IBD. Further investigations are needed to explore the causal effect of estrogen on IBD activity and the underlying mechanism of estrogen in IBD.

All women with multiple sclerosis should start hormone replacement therapy at menopause unless contraindicated: No

All women with multiple sclerosis should start hormone replacement therapy at menopause unless contraindicated: No

Bone mineral density: Comparison between women under hormone replacement therapy with Turner syndrome or idiopathic premature ovarian insufficiency

ContextTurner syndrome (TS) is characterized by short stature and premature ovarian insufficiency (POI). The main long-term complication of POI is osteoporosis, which can be prevented by hormone replacement therapy (HRT). ObjectiveThe objective of our study was to compare initial bone mineral density (BMD) and progression between TS and idiopathic POI patients under HRT. MethodsA single-center retrospective study was conducted between 1998 and 2018. All women had undergone at least two bone densitometry assessments at least 2 years apart. ResultsSixty-eight TS patients and 67 idiopathic POI patients were included. Mean age at initial assessment was 27 years (IQR, 21–35.5 years) in TS patients and 31.5 years (IQR, 23–37 years) in idiopathic POI patients (P=0.1). Lumbar and femoral neck BMD were lower in the TS group than in the idiopathic POI group (respectively 0.89g/cm2 versus 0.95g/cm2, P=0.03; 0.70g/cm2 versus 0.77g/cm2, P<0.0001). Mosaic karyotype was associated with better BMD in TS patients while history of growth hormone treatment had no impact on BMD. Over time, a significant gain in vertebral BMD was observed in TS patients versus a loss of BMD in idiopathic POI patients (P=0.0009). ConclusionTS patients had a lower BMD at baseline than idiopathic POI patients, at both spinal and femoral levels. Over time, on HRT, a significant gain in vertebral BMD was observed in patients with TS, compared with a loss of BMD in patients with idiopathic POI. We hypothesized that earlier initiation and longer duration of HRT played an important role in this finding. Long-term prospective follow-up to assess the incidence of fractures in TS would be useful.

First successful ovarian cortex allotransplant to a Turner syndrome patient requiring immunosuppression: wide implications

ObjectiveTo determine whether we can safely and successfully transplant an ovary tissue allograft from a non-identical donor to her Turner syndrome sister. DesignTransplantation of cryopreserved ovary tissue, as well as fresh transplantation of ovarian tissue between identical twins, is now well established with numerous reported successful cases. However there have not yet been any ovary transplants between non-identical women requiring immunosuppression (ovary allotransplant). This could be a much more common indication for ovary tissue transplantation if safe and reliable immunosuppression were available. SubjectsA 20 year old amenorrheic woman with non-mosaic 45-XO Turner syndrome requested ovary tissue transplantation from her fertile 22 year old 46-XX sister. They were an HLA match but were ABO incompatible, a well known contra-indication to solid tissue or organ transplantation. The Turner syndrome sister strongly preferred to be able to become pregnant naturally without donor egg IVF, and to avoid HRT (hormone replacement therapy). In her religious group, that would also be important for finding a marital match. Despite the poor prognosis associated with ABO incompatibility, an ovary from her 22 year old non-identical fertile sister was transplanted to her employing the immunosuppression protocol now used for kidney transplant patients in our centers at Washington University and Johns Hopkins. Main Outcome MeasuresPost-operatively at 5 months she developed normal monthly menstrual ovarian function, and she became spontaneously pregnant with a normal baby girl. The relation between her post-op FSH and AMH levels continues to support the theory that tissue pressure controls primordial follicle recruitment. The fact that ABO incompatibility did not prevent success suggests that diffusion and not revascularization may be all that is required for successful long term ovarian cortex transplant survival with spontaneous pregnancy. ResultsOvary allotransplantation with safe immunosuppression allows natural conception, and also normal hormone function obviates the need for HRT. Orthotopic placement of the graft and surgical technique is critical for natural conception and a higher pregnancy rate. ConclusionAllotransplantation requiring safe immunosuppression, if successful, may be a much more commonly used indication for ovary transplantation in the future than frozen ovary grafts or grafts between identical twins.

Efficacy and Safety of Intravaginal Estrogen in the Treatment of Atrophic Vaginitis: A Systematic Review and Meta-Analysis.

Postmenopausal females often experience genitourinary symptoms like vulvovaginal dryness due to estrogen decline. Hormone replacement therapy is effective in alleviating vaginal atrophy and genitourinary syndrome in this population. Evaluate local estrogen's safety and effectiveness for alleviating postmenopausal vaginal symptoms, including endometrial thickness, dyspareunia, vaginal pH, and dryness. We searched Google Scholar, Cochrane Library, ClinicalTrial.Gov, PubMed, and ScienceDirect databases until July 2023. All randomized controlled trials (RCTs) linking intravaginal estrogen supplementation to vaginal atrophy or vaginitis were included. The risk of bias was evaluated with RoB 2, and publication bias was assessed using Egger and Beggs analysis. All evidence pertains to females. Eighteen studies (n = 4,723) compared estrogen with placebo. Patients using estrogen showed a significant increase in superficial cells (mean differences [MD]: 19.28; 95% confidence intervals [CI]: 13.40 to 25.16; I² = 90%; P < 0.00001) and a decrease in parabasal cells (MD: -24.85; 95% CI: -32.96 to -16.73; I² = 92%; P < 0.00001). Vaginal pH and dyspareunia significantly reduced in estrogen users (MD: -0.94; 95% CI: -1.05 to -0.84; I² = 96%) and (MD: -0.52; 95% CI: -0.63 to -0.41; I² = 99%), respectively. Estrogen did not significantly affect vaginal dryness (MD: -0.04; 95% CI: -0.18 to 0.11; I² = 88%). Adverse events like vulvovaginal pruritis, mycotic infection, and urinary tract infection were reported, but the association was insignificant (risk ratio: 0.95; 95% CI: 0.88 to 1.02; I² = 0%). Our meta-analysis of 18 RCTs suggests promising potential for intravaginal estrogen therapy in alleviating vaginal atrophy and vaginitis in postmenopausal females.

Acupuncture combined with gonadotropin-releasing hormone agonists improves endometrial receptivity and pregnancy outcome in patients with recurrent implantation failure of in vitro fertilization-embryo transfer.

Gonadotropin-releasing hormone agonists (GnRHa), combined with other auxiliary treatments, can improve pregnancy outcomes in in vitro fertilization-embryo transfer (IVF-ET). This research investigated the effect of acupuncture combined with GnRHa in patients with recurrent implantation failure (RIF) of IVF-ET. A total of 164 patients who intended to undergo frozen-thawed embryo transfer after RIF of IVF-ET were selected for experiments and then divided into the control (received conventional hormone replacement therapy (HRT) for endometrial preparation) and study groups (received a combination of acupuncture, GnRHa, and HRT for endometrial preparation) (n = 82). Endometrial thickness (EMT), endometrial morphological classification, submucosal uterine blood flow classification, clinical pregnancy rate, embryo implantation rate, and early abortion rate for each transfer cycle were compared between the two groups. EMT of the study group was higher than that of the control group 1 day before transfer. There were more patients with linear endometrium (A + B type) in the study group on the day of endometrial transformation than in the control group. The number of patients with type I submucosal uterine blood flow in the study group was decreased and the number of patients with type III was increased compared with the control group on the day of endometrial transformation. The clinical pregnancy rate and embryo implantation rate of the study group were higher than those of the control group. Acupuncture combined with GnRHa improves the endometrial receptivity of patients with RIF of IVF-ET, thereby increasing clinical pregnancy rates and improving pregnancy outcomes.

All women with multiple sclerosis should start hormone replacement therapy at menopause unless contraindicated: Commentary

All women with multiple sclerosis should start hormone replacement therapy at menopause unless contraindicated: Commentary