Extensive post reproductive lifespan (PRLS) is observed only in a few species, such as humans or resident killer whales, and its origin is under debate. Hypotheses like mother-care and grandmother-care invoke strategies of investment—provision to one’s descendants to enhance one’s overall reproductive success—to explain PRLS. The contribution of an investment strategy varies with the age of the caregiver, as the number of care-receiving descendant changes with age. Here we simulated an agent based model, which is sensitive to age-specific selection, to examine how the investment strategies in different hypotheses affect survival and reproduction across different stages of life. We found that extensive PRLS emerges if we combine multiple investment strategies, including grandmother-care but not mother-care, which allow an individual to have an increasing contribution as it ages. We also found that, if mother-care is further introduced to the PRLS-enabling strategies, it will let contribution at mid-life to substitute contribution at late life, which consequently terminates extensive PRLS.

Menopause is the last step in the reproductive history of a woman. The ovaries stop producing hormones and the body reacts by lowering its functions, including the neuronal one. Phytoestrogens are plant products with estrogen-like activity able to affect many body functions. The aim of the present experiment was to study the effects of 30 days of regular consumption of a soy-enriched bread containing a known amount of phytoestrogens (genistein and daidzein). Women at climacteric, within 5 years or more than 5 years of menopause, were asked to include in their diet 200 g/day of a bread containing 40 mg of phytoestrogens. The effect on common menopausal symptoms and neurophysiological, hormonal and antioxidant parameters were determined before and after 30 days through questionnaires and experimental tests. Phytoestrogens were measured in the urine. In all groups, there was a significant increase of phytoestrogens in the urine and a decrease of the classical symptoms of menopause as well as a significant improvement in attentional performance tests, the quality of life index and pain intensity. Phytoestrogens present in the soy-enriched bread, are an important supplement in aging women due to their ability to induce estrogen-like effects without the potential side effects of estrogens.

Platelets are a uniquely mammalian physiologic attribute. As the only non-marine vertebrate class to experience menopause, humans have a substantial post-reproductive lifespan and are believed to have a limited, non-renewable oocyte supply. Ovarian reserve typically declines after about age 35yrs, marking losses which cannot be recovered by available fertility medications. When in vitro fertilization fails due to low or absent ovarian response, gonadotropin adjustments are often ineffectual and if additional oocytes are occasionally harvested, egg quality is usually poor. This problem was confronted by Greek researchers who developed a new surgical method to insert autologous platelet-rich plasma (PRP) into ovaries; the first ovarian PRP success to improve reproductive outcomes was published from Athens in 2016. This innovation influenced later research with condensed platelet-derived growth factors, leading to correction of oocyte ploidy error, normal blastocyst development, and additional term livebirths. Yet women’s health was among the last clinical domains to explore PRP, and its role in ‘ovarian rejuvenation’ remains unsettled. One critical aspect in this procedure is platelet activation, a commonly overlooked step in the cytokine release cascade considered essential for successful transition of undifferentiated ovarian stem cells to an oocyte lineage. Poor activation of platelets thus becomes an unforced error, potentially diminishing or even negating post-treatment ovarian follicular response. To answer this query, relevant theory, current disagreements, and new data on platelet activation are presented, along with clinical challenges for regenerative fertility practice.

The first published description of intraovarian platelet-rich plasma (PRP) appeared in mid-2016, when a new experimental technique was successfully used in adult human ovaries to correct the reduced fertility potential accompanying advanced maternal age. Considering the potential therapeutic scope of intraovarian activated PRP and/or condensed platelet cytokines would likely cover both menopause treatment and infertility, the mainstream response has ranged from skeptical disbelief to welcome astonishment. Indeed, reports of restored menses in menopause (as an alternative to conventional hormone replacement therapy) and healthy term livebirths for infertility patients (either with IVF or as unassisted conceptions) after intraovarian PRP injection continue to draw notice. Yet any proper criticism of ovarian PRP applications will be difficult to rebut given the heterogenous patient screening, varied sample preparations, wide differences in platelet incubation and activation protocols, surgical/anesthesia techniques, and delivery methods. Notwithstanding these features, no adverse events have been reported thus far and ovarian PRP appears well tolerated by patients. Here, early research guiding the transition of ‘ovarian rejuvenation’ from experimental to clinical is outlined. Likely mechanisms are presented to explain results observed in both veterinary and human ovarian PRP research. Current and future challenges for intraovarian cytokine treatment are also discussed.

Background: Menopause symptoms and hormone replacement therapy (HRT) are among the most common reasons patients seek gynecological advice. Although at least half of all women in developed countries will take HRT during their lifetime, the treatment is not without risk and guidance on HRT is mixed. Greater awareness of negative HRT health effects from extended use has piqued interest in ‘safer options’. Menopause reversal with autologous ovarian platelet-rich plasma (OPRP) has brought this restorative approach forward for consideration, but appropriateness and cost-effectiveness require examination. Methods: HRT and OPRP data from USA were projected to compare cumulative 1yr patient costs using stochastic Monte Carlo modeling. Results: Mean±SD cost-to-patient for HRT including initial consult plus pharmacy refills was estimated at about USD 576±246/yr. While OPRP included no pharmacy component, an estimated 4 visits over 1yr for OPRP maintenance entailed ultrasound, phlebotomy/sample processing, surgery equipment, and incubation/laboratory expense, yielding mean±SD cost for OPRP at USD 8,710±4,911/yr (p<0.0001 vs. HRT, by t-test). Upper-bound estimates for annual HRT and OPRP costs were USD 1,341 and USD 22,232, respectively. Conclusions: While HRT and OPRP may have similar efficacy and safety for menopause therapy, they diverge sharply in cost-effectiveness. Most patients would likely find OPRP too complex, invasive, and expensive to be competitive vs. HRT. Although OPRP is an interesting and cautiously useful technique for selected menopause patients reluctant to use HRT, repurposing this infertility treatment for wider use appears inefficient compared to standard HRT currently available.

Purpose: Hormone Replacement Therapy (HRT), an FDA-approved treatment for menopausal conditions was found to be associated with increased risk of endometrial cancer and reduced oestrogen. Studies showing benefits of HRT in preventing chronic diseases lead to development of clinical guidelines by American College of Physicians. This study aims to assess effectiveness of HRT treatments across cardiometabolic measures including Triglycerides (TG), Follicle-Stimulating Hormone, LDL cholesterol, HDL cholesterol, and Estradiol in menopausal women. It reports gaps in scientific knowledge and clinical practice to enhance current guidelines and policies.Methods: A systematic methodology designed and published in PROSPERO (CRD42022346057) to report network meta-epidemiology analysis was utilised. We used databases by PubMed, Web of Science, ScienceDirect, EMBASE and MEDLINE for studies published between 30th of April 1980-2022. Effects of HRT treatments were explored using a mixed treatment comparison (MTC) model. Fixed and random-effects models were used to address heterogeneity in published studies. Publication bias was assessed and corrected using funnel plots and Egger’s test.Results: Of 45 eligible studies, our findings indicate a significant statistical heterogeneity between HRTs and reduction of TG, SFH, LDL-C alongside increase of HDL-C and Estradiol among menopausal women. The analysis suggests a lack of direct evidence to support their efficacy in reducing TG, SFH and LDL-C levels or to substantiate HRT’s effectiveness in increasing HDL-C and Estradiol. The results showed no significant publication bias in the meta-analysis of included studies.Conclusion: Our findings demonstrate that use of HRT interventions among menopausal women may reduce TG, FSH and LDL-C levels and increase levels of HDL-C and estradiol via oral and oral + transdermal administration. Our study reaffirms efficacy of HRT in supporting favourable lipid profile in menopausal women whilst highlighting the need for robust and inclusive epidemiology studies and clinical trials to further develop clinical guidelines and policies.

As a result of scientific technological advancements in medical diagnostics, treatment modalities of non-communicable and communicable diseases, and palliative care approaches, the life expectancy of women is soaring than men across the globe, due to the longer telomere length and other protective factors. The main symptoms of menopause broadly be divided into psychological somatovegetative and urogenital. Neglected menopausal symptoms can lead to debilitating comorbidities which may end up in mortalities. Fortunately, modern treatment and therapeutic formalities based on pharmaceutical preparations, as well as lifestyle- modifications have provided long-lasting relief for the pre-menopausal woman. This can be done as per her preference if she is knowledgeable, resourceful, and cheerful. Menarchae is the “ alpha” and menopause is the “omega” phase in the reproductive lifecycle of any woman. Reproductive health is essentially an integral part of women’s health. In this 4^th industial revolution era information technology and digital science go hand in hand to improve the quality of life of populations across the globe irrespective of their educational and professional status. Health literacy among disadvantageous sub populations increased. Positive attitudes, perception and evidence-informed knowledge on adolesecent girls about not only ‘period pains’ but menopausal symptoms as an inevitable phase in a woman’s reproductive health may make a better sense at the dawn of evidence based medicine even in a low middle income country like Sri Lanka. Hence, this timely communication strengthens by, Do not fear when menopause is near: The Importance of a Preparatory Time and Space to face the consequences of Menopaus. How to forget the fact that alpha and the omega are inevitable phases in woman’s reproductive health trajectory. Moreover, the importance of a preparatory time and space well in advance preferably in peri-menopausal time to prevent and control the inevitable health consequences. Moreover, to invest in menopause for a brighter future in the modern personalized medicine era based on global scientific evidence.

Background: Assessing the impact of bone health clinical management in breast cancer (BC) patients receiving adjuvant endocrine therapy and designing a personalized clinical pathway to reduce bone loss, in an Italian research hospital. Methods: The primary endpoint was to assess (through the process improvement organizational method) the clinical pathway that post-surgical BC patients prescribed with endocrine therapy undergo to prevent bone loss. The secondary endpoint was to design a personalized clinical pathway for a prompt implementation of guidelines, to assess and possibly prescribe antiresorptive therapy. Results: During the first year of the new diagnostic therapeutic assistance pathway execution, an 60% increase in Dual-Energy X-ray Absorptiometry evaluations within 30 days and a 39.5% increase in antiresorptive therapy prescription within 90 days (since prescription of endocrine therapy) were shown, thus increasing patients’ compliance. Conclusion: Case managers and bone health specialists in this context can improve patients’ adherence to therapies and bone health, helping physicians to expand their collaboration.

Urethral prolapse (UP) is a rare condition in which the distal urethral mucosa protrudes circularly from the external urethral meatus. Urethral prolapse is seen in two age groups: prepubertal girls and postmenopausal women. The fact that it is seen in older women shows that it may be acquired. Causes of acquired UP include weakening of smooth muscle layers secondary to estrogen deficiency, chronic cough, chronic constipation, trauma, recurrent urinary tract infections, pelvic radiotherapy, and sexual abuse. The priority in treatment is conservative management, such as manual reduction, sitz baths, topical estrogen creams, and antibiotics. The general consensus is to switch to surgical treatment in patients who do not benefit from a conservative approach. In this case report, we describe the surgical treatment of a 56-year-old postmenopausal female patient with necrotic UP who presented with urinary retention.

Estrogen decline during menopause is associated with altered metabolism, weight gain and increased risk for cardiometabolic diseases. The gut microbiota also plays a role in the development of cardiometabolic dysfunction and is also subject to changes associated with age-related hormone changes. Phytoestrogens are plant-based estrogen mimics that have gained popularity as dietary supplements for treatment or prevention of menopause-related symptoms. These compounds have the potential to both modulate and to be metabolized by the gut microbiota. Hops (Humulus lupulus L.) contain potent phytoestrogen precursors, which rely on microbial biotransformation in the gut to estrogenic forms. We supplemented ovariectomized (OVX) or sham-operated (SHAM) C57BL/6 mice, with oral estradiol (E2), a flavonoid-rich extract from hops, or a placebo carrier oil to observe effects on adiposity, inflammation, and gut bacteria composition. Hops extract and E2 protected against increased visceral adiposity and liver triglyceride accumulation in OVX animals. Surprisingly, we found no evidence of OVX having a significant impact on the overall gut bacterial community structure. We did find differences in abundance of Akkermansia muciniphila, which was lower with HE treatment relative to the OVX E2 treatment and to placebo in the SHAM group.

Postmenopausal abnormal uterine bleeding is a common clinical problem addressed in gynecological practice and should prompt clinical investigation due to the significant prevalence of malignant and premalignant lesions of endometrium in this age group. Nevertheless, other causes should be considered since its diagnostic and therapeutic management may differ considerably. Here, we present a case of a colouterine fistula due to chronic diverticulitis presenting with postmenopausal abnormal uterine bleeding. This is extremely rare and is caused by the rupture of a diverticular abscess into the uterine wall, resulting in an inflammatory adhesion of the colon and uterus, with necrosis and subsequent fistula formation. The clinical presentation is variable and may include abdominal pain, gastrointestinal tract symptoms, vaginal discharge and abnormal uterine bleeding. The laboratory and imaging techniques may be not completely conclusive and definitive diagnosis can be made intraoperatively. There are different treatment options, being the en bloc resection and primary anastomosis the most used, allowing complete treatment. The prognosis for a colouterine fistula secondary to diverticulitis is excellent after surgery. This case highlights the importance of clinical suspicion of an unusual cause of uterine bleeding and an effective and multidisciplinary approach that allowed complete surgical treatment and patient recovery.

Long-term safety of a nutraceutical combination based on agnus castus and magnolia extracts combined with soy isoflavones (SI) and lactobacilli, and effectiveness on vasomotor symptoms and sleep disorders in postmenopausal women, were assessed. A controlled study was carried-out in menopausal women comparing this nutraceutical combination (ESP group) with formulation containing isoflavones alone (C group), at the dosage recommended. Kuppermann index, PSQI, and SF-36 were determined at baseline, 3, 6 and 12 months. Endometrial thickness, mammary density and liver function were evaluated at baseline and after 12 months. 180 women (100 in ESP group and 80 in C group, mean age 55.5 years, in menopause for about 36 months) were enrolled in the study. At the treatment end, mammary density, endometrial thickness, and hepatic function did not show substantial differences between groups. Kuppermann index, and particularly hot flushes, were progressively and significantly decreased in frequency and severity during ESP versus C treatment. No adverse events were observed. Agnus castus and magnolia, combined with SI + lactobacilli, can effectively and safely be used in symptomatic postmenopausal women, mainly when quality of sleep is the most disturbing complaint. Endometrium, mammary glands and liver function, were unaffected after 12 months treatment.

The menopausal transition often accompanies distressing manifestations, including vasomotor symptoms, sleep disruptions, and depressive syndrome. Omega-3 fatty acids have emerged as a potential intervention to alleviate these symptoms. This review aimed to comprehensively assess the impact of omega-3 supplementation on vasomotor symptoms, sleep quality, and depression among postmenopausal women. We conducted a systematic search focusing on randomized control trials across the Cochrane Library, Web of Science, PubMed, CINAHL, EMBASE, and SCOPUS databases from inception to August 2023. Among the initial pool of 163 studies, 9 studies met the inclusion criteria and were incorporated into this review. Four studies suggested potential benefits of omega-3 intake for improving hot flashes and night sweats. Sleep quality outcomes displayed heterogeneity across the studies. Incorporating diverse scales such as the Hamilton Depression Rating Scale-21, the Patient Health Questionnaire depression scale, and Generalized Anxiety Disorder-7 for depression outcomes, the review found inconclusive evidence on omega-3's impact on depression. Overall, the combined analysis of these studies did not provide substantial evidence to support the efficacy of omega-3 fatty acids in improving vasomotor symptoms, sleep quality, and depression. Further well-designed RCTs with larger participant groups are crucial to validate and generalize these results.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition among postmenopausal women that can lead to severe liver dysfunction and increased mortality. In recent years, research has focused on identifying potential lifestyle dietary interventions that may prevent or treat NAFLD in this population. Due to the complex and multifactorial nature of NAFLD in postmenopausal women, the disease can present as different subtypes, with varying levels of clinical presentation, and variable treatment responses. By recognizing the significant heterogeneity of NAFLD in postmenopausal women, it may be possible to identify specific subsets of individuals who may benefit from targeted nutritional interventions. In this review, we sought to examine the current evidence supporting the role of three specific nutritional factors - choline, soy isoflavones, and probiotics – as potential nutritional adjuvants in the prevention and treatment of NAFLD in postmenopausal women. There is promising evidence supporting the potential benefits of these nutritional factors for NAFLD prevention and treatment, particularly in postmenopausal women, and further research is warranted to confirm their effectiveness in alleviating hepatic steatosis in this population.

We aimed to evaluate the association between daily dietary calcium intake and the risk of cardiovascular disease (CVD) in postmenopausal women using data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study included 12,348 women aged 45–70 years who had reached natural menopause. They were classified into three groups according to daily dietary calcium intake: &lt; 400 mg, 400–800 mg, and &gt;800 mg. The risks of CVD, stroke, angina, and myocardial infarction were assessed in each group. Further, we performed subgroup analysis according to the post-menopause duration (≤10 vs. &gt;10 postmenopausal years). We performed logistic regression analysis with adjustment for age, menopausal age, income, urban area, education, insulin use, body mass index, hypertension, diabetes mellitus, dyslipidemia, high alcohol intake, smoking, exercise, oral contraceptive use, and hormonal therapy use. Calcium intake level was not significantly associated with the risk of CVD in the total population and the ≤10 postmenopausal years subgroup. However, in the &gt;10 postmenopausal years subgroup, daily calcium intake &gt;800 mg was associated with significantly decreased risks of all CVD (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.11–0.64), stroke (OR, 0.06; 95% CI, 0.01–0.42), and myocardial infarction (OR, 0.27; 95% CI, 0.11–0.64). Our findings suggest that a dietary calcium intake of &gt;800 mg/day decreases the risk of CVD events in women who have been menopausal for &gt;10 years.

Premature ovarian insufficiency (POI) is a highly prevalent disorder, characterized by the development of menopause before age of 40. Most cases are idiopathic; however, in some women the cause of this condition (e.g. anticancer treatment, genetic disorders, and enzymatic defects) may be identified. Although hormone replacement therapy, the principal therapeutic approach for POI, helps to alleviate the related symptoms, this does not effectively solve the issue of fertility. Assisted reproductive techniques also lack efficacy in these women. Thus, the effective approach to manage the patients with POI is highly warranted. Several mechanisms, associated with POI, have been identified, including lack of FSH receptor functioning, alterations in the apoptosis control, mutations in Sal-like 4 genes, thymulin or basonuclin-1 deficiency etc. The above-mentioned may be good targets for gene therapy in order to correct defects, leading to POI. The goal of this review is to summarize the current experience on the POI studies, that employed gene therapy, and to discuss the possible future directions in this field.