Aging and Adiposity-Focus on Biological Females at Midlife and Beyond.

Menopause is a physiological phase of life of aging women, and more than 1 billion women worldwide will be in menopause by 2025. The processes of global senescence parallel stages of reproductive aging and occur alongside aging-related changes in the body. Alterations in the endocrine pathways accompany and often predate the physiologic changes of aging, and interactions of these processes are increasingly being recognized as contributory to the progression of senescence. Our goal for this review is to examine, in aging women, the complex interplay between the endocrinology of menopause transition and post-menopause, and the metabolic transition, the hallmark being an increasing tendency towards central adiposity that begins in tandem with reproductive aging and is often exacerbated post menopause. For the purpose of this review, our choice of the terms 'female' and 'woman' refer to genetic females.

Testosterone-associated blood pressure dysregulation in women with androgen excess polycystic ovary syndrome.

We tested the hypothesis that hyperandrogenemia in androgen excess polycystic ovary syndrome (AE-PCOS) is a primary driver in blood pressure (BP) dysregulation via altered sympathetic nervous system activity (SNSA), reduced integrated baroreflex gain and increased renin-angiotensin system (RAS) activation. We measured resting SNSA (microneurography), integrated baroreflex gain, and RAS with lower body negative pressure in obese insulin-resistant (IR) women with AE-PCOS [n = 8, 23 ± 4 yr; body mass index (BMI) = 36.3 ± 6.4 kg/m2] and obese IR controls (n = 7, control, 29 ± 7 yr; BMI = 34.9 ± 6.8 kg/m2), at baseline (BSL), after 4 days of gonadotropin-releasing hormone antagonist (ANT, 250 µg/day) and 4 days of ANT + testosterone (ANT + T, 5 mg/day) administration. Resting BP was similar between groups for systolic blood pressure (SBP; 137 ± 14 vs. 135 ± 14 mmHg, AE-PCOS, control) and diastolic BP (89 ± 21 vs. 76 ± 10 mmHg, AE-PCOS, control). BSL integrated baroreflex gain was similar between groups [1.4 ± 0.9 vs. 1.0 ± 1.3 forearm vascular resistance (FVR) U/mmHg], but AE-PCOS had lower SNSA (10.3 ± 2.0 vs. 14.4 ± 4.4 burst/100 heartbeats, P = 0.04). In AE-PCOS, T suppression increased integrated baroreflex gain, which was restored to BSL with ANT + T (4.3 ± 6.5 vs. 1.5 ± 0.8 FVR U/mmHg, ANT, and ANT + T, P = 0.04), with no effect in control. ANT increased SNSA in AE-PCOS (11.2 ± 2.4, P = 0.04). Serum aldosterone was greater in AE-PCOS versus control (136.5 ± 60.2 vs. 75.7 ± 41.4 pg/mL, AE-PCOS, control, P = 0.04) at BSL but was unaffected by intervention. Serum angiotensin-converting enzyme was greater in AE-PCOS versus control (101.9 ± 93.4 vs. 38.2 ± 14.7 pg/mL, P = 0.04) and reduced by ANT in AE-PCOS (77.7 ± 76.5 vs. 43.4 ± 27.3 µg/L, ANT, and ANT + T, P = 0.04) with no impact on control. Obese, IR women with AE-PCOS showed decreased integrated baroreflex gain and increased RAS activation compared with control.NEW & NOTEWORTHY Here we present evidence for an important role of testosterone in baroreflex control of blood pressure and renal responses to baroreceptor unloading in women with a common, high-risk androgen excess polycystic ovary syndrome (AE-PCOS) phenotype. These data indicate a direct effect of testosterone on the vascular system of women with AE-PCOS independent of body mass index (BMI) and insulin-resistant (IR). Our study indicates that hyperandrogenemia is a central underlining mechanism of heightened cardiovascular risk in women with PCOS.

Genital tuberculosis, infertility and assisted reproduction.

PURPOSE OF REVIEW: The goal of this review is to familiarize a global readership on the subtilities of clinical presentation and the mayhem that a missed diagnosis of genital tuberculosis (GTB) is capable of inflicting on the health and wellbeing of infertile women with untreated GTB attempting to conceive with assisted reproductive technology (ART). RECENT FINDINGS: Emerging and recent literature relating to the epidemiology and clinical presentation of GTB and reporting of unique risks of ART for maternal and fetal morbidity in untreated cases of GTB are reviewed. Evidence relating to a broadening spectrum of screening methodologies for GTB detection of GTB is additionally considered. SUMMARY: Genital TB must be considered as a mechanism for couple's infertility in at-risk populations. Attempting to treat female GTB-related infertility with in-vitro fertilization poses unique and potentially life-threatening risks, both to the mother and to the conceptus; these risks can be avoided through vigilance, appropriate screening and timely treatment prior to proceeding with IVF.

Vitamin D and infertility.

PURPOSE OF REVIEW: Vitamin D deficiency has been implicated as a contributing factor to a spectrum of reproductive health burden, including difficulty conceiving, pathogenesis of gynaecological disorders such as uterine fibroids and endometriosis, to metabolic and endocrine burden of polycystic ovarian syndrome (PCOS). RECENT FINDINGS: There have been recent publications showing that in infertile women who are supplemented with vitamin D, there are higher pregnancy rates; there are improved ovarian reserve parameters in women with diminished ovarian reserve; curtailed fibroid growth in those with uterine myomas; lessened dysmenorrhea in endometriosis patients; and improved menstrual regularity, lowered testosterone, AMH and insulin levels in women with PCOS. In infertile men, sperm parameters, especially motility, are positively correlated with vitamin D serum levels. SUMMARY: Vitamin D status appears to be relevant to reproductive physiology, and to physiological processes underlying common gynaecological disorders as well as for reproductive success.

Racial disparities in access to reproductive health and fertility care in the United States.

PURPOSE OF REVIEW: To examine the status of racial and ethnic inequalities in fertility care in the United States (U.S.) at inception of 2022. This review highlights addressable underpinnings for the prevalent differentials in access to and utilization of infertility treatments and underscores gaps in preventive care as key contributors to racial and ethnic disparities in risk burden for subfertility and infertility. RECENT FINDINGS: Significant gaps in access to and utilization of fertility care are consistently reported among racial and ethnic minorities, particularly Black and Hispanic women. Access to and utilization of contraceptives, human papilloma virus vaccination rates, preexposure prophylaxis use, and differentials in treatment of common gynecologic disorders are relevant to the prevalent racial and ethnic disparities in reproductive health. The spectrum of differential in reproductive wellness and the magnitude of reproductive health burden afflicting racial minorities in the U.S. raise concerns regarding systemic and structural racism as plausible contributors to the prevalent state of affairs. SUMMARY: Despite efforts to reform unequal reproductive health practices and policies, racial and ethnic disparities in fertility care are pervasive and persistent. In addition to measures aimed at reducing barriers to care, societal efforts must prioritize health disparity research to systematically examine underpinnings, and addressing structural racism and interpersonal biases, to correct the prevalent racial inequities and mitigate disparities.

The Diagnostic Criteria for Chronic Endometritis: A Survey of Pathologists.

While acute endometritis is a reasonably well-defined entity of ascending infection and attendant active inflammation, chronic endometritis is less well defined. As part of a broad effort to define and refine the diagnostic criteria and management of the disease, we conducted a survey of pathologists to understand the variability in diagnostic criteria and implications of the diagnosis of nonspecific, nonobstetric chronic endometritis. Members of national and international professional pathology societies were surveyed utilizing anonymous electronic surveys designed to examine diagnostic criteria, etiological understanding and treatment implications of a pathologic diagnosis of nonspecific, nonobstetric chronic endometritis. There was substantial variability among pathologists in the diagnostic criteria used for making a diagnosis of nonspecific, nonobstetric chronic endometritis, with 28.5% of pathologists using the presence of a single plasma cell for making the diagnosis. There was additional variability in the use of special stains, reporting in the presence of coexisting lesions and the hormonal stage of the endometrium. There were no differences between generalists and specialists in the diagnostic criteria used, except the significantly greater likelihood of specialists making the diagnosis in gestational endometrium. The substantial variability in diagnostic criteria for nonspecific, nonobstetric chronic endometritis among pathologists, including among gynecologic pathologists, has the potential to confound the management of patients. Standardization of diagnostic criteria for chronic endometritis is essential to understand the implications of the diagnosis.

Eliminating Hormones With Orally Active Gonadotropin-releasing Hormone Antagonists.

Gonadotropin-releasing hormone (GnRH) analogues have been used in clinical practice for nearly 3 decades. Beginning with GnRH agonists, these agents have been used to treat hormone-dependent disease and to suppress gonadotropin production in assisted reproductive technologies. With the development of GnRH antagonists and especially small-molecule antagonists, our ability to achieve gonadotropin and sex steroid suppression has become increasingly effective and convenient. In this review, we will briefly describe the development of GnRH analogues, review the evolution of orally active small-molecule GnRH antagonists and provide an overview of the expanding role of small-molecule GnRH antagonists in clinical practice.

A Narrative Review of Current Understanding of the Pathophysiology of Polycystic Ovary Syndrome: Focus on Plausible Relevance of Vitamin D.

Polycystic ovarian syndrome (PCOS) is the most prevalent endocrinopathy of reproductive years. Salient features in presentation of patients PCOS include menstrual dysfunction, hyperandrogenism and/or polycystic appearance of ovaries on ultrasound. While the diagnosis of PCOS depends on presence of specified criteria, misdiagnoses are common. Despite years of extensive research, the exact aetiology of PCOS remains largely unknown. In the past decade, apart from insulin resistance and hyperandrogenemia, anti-mullerian hormone (AMH), an important marker of ovarian reserve, and vascular endothelial growth factor (VEGF), a crucial factor in angiogenesis, have been examined as plausible players of causative relevance for PCOS. Vitamin D, a sex-steroid hormone that is universally known for its relevance for skeletal health, has received increasing attention due to growing evidence supporting its pivotal in reproductive physiology and in PCOS. In this review we summarize our current understanding of the mechanisms relevant to the pathophysiology of PCOS and examine the role of vitamin D signalling in this context.

Thermal stability of cytokines: A review.

BACKGROUND: The role of cytokines in various disease states is a burgeoning field of academic study and clinical application, however there are no consensus documents on how certain cytokines should be stored prior to quantification. This information is especially of interest to researchers assembling a biobank or clinicians who have to transport specimens to a different location in order to be tested. OBJECTIVE: To review the literature and synthesize prior findings on cytokine storage and freeze/thaw stability. DESIGN: We searched PubMed for articles related to cytokine storage stability. All articles were analyzed for cytokines studied, source of reported cytokine concentration (i.e., human whole blood or serum, concentrations from other species or bodily sources were excluded), and reported statistical results. RESULTS: We identified and synthesized results of 23 peer-reviewed articles which published data on the storage and freeze/thaw stability of 33 different cytokines and chemokines. CONCLUSION: There is a wide variety of reported cytokine storage and freeze/thaw stability. Interleukin-6 and tumor necrosis factor alpha are the most widely studied cytokines in regard to temperature stability. In a few cytokines, a clear consensus can be reached as to storage safety at particular temperatures, but in most, more research needs to be done and we advise the clinician or researcher to use caution in interpreting cytokine concentration results after a long period of storage or several freeze/thaw cycles.

Genital tuberculosis screening at an academic fertility center in the United States.

BACKGROUND: Infertility is a common presentation of female genital tuberculosis in endemic areas. Female genital tuberculosis-related maternal and neonatal complications have increased in recent years after assisted reproductive technology treatments. Despite rising emigration rates to the United States, guidelines to identify those with latent tuberculosis or female genital tuberculosis in fertility centers do not exist. OBJECTIVE: This study aimed to characterize the prevalence of female genital tuberculosis in infertile patients at our academic fertility center. STUDY DESIGN: This is a prospective cohort study. All patients presenting for infertility evaluation between January 2014 and January 2017 were assessed for risk factors for latent tuberculosis. Patients at risk for latent tuberculosis underwent screening using QuantiFERON-TB Gold serum assay. QuantiFERON-TB Gold-positive patients underwent further testing for female genital tuberculosis consisting of endometrial biopsy with histopathologic examination by a clinical pathologist, polymerase chain reaction for tuberculosis, and culture for acid-fast Mycobacterium tuberculosis. RESULTS: Twenty-five of 323 infertility patients (7.7%) screened for latent tuberculosis had positive QuantiFERON-TB Gold results. A greater number of patients with a positive test result for QuantiFERON-TB Gold were foreign born than those with a negative test result for QuantiFERON-TB Gold (92% vs 29%; P<.001). Of note, the QuantiFERON-TB Gold-positive population had a higher incidence of both recurrent pregnancy loss (28% vs 7%; P=.003) and Asherman syndrome (8% vs 0.3%; P<.001). Among those with a positive test result for QuantiFERON-TB Gold, chest x-ray was abnormal in only 2 patients (8.0%). Endometrium evaluation revealed abnormalities in 2 patients (8.0%), in whom chest x-ray was normal, with 1 showing evidence of female genital tuberculosis. This was indicated by histology consistent with chronic granulomatous endometritis and positive endometrial testing for tuberculosis by polymerase chain reaction, acid-fast bacilli smear, and culture for Mycobacterium tuberculosis. CONCLUSION: Although the prevalence of female genital tuberculosis in infertile women in the United States seems to be low, this study indicates that it can be underdiagnosed without utilization of multiple diagnostic modalities including endometrial sampling. Given the potential for serious maternal and neonatal morbidity in affected patients utilizing assisted reproductive technology, we propose that all at-risk women seeking infertility care in the United States be screened for latent tuberculosis. In patients who screen positive, endometrial biopsy should be obtained for evaluation by histology, polymerase chain reaction, and culture for Mycobacterium tuberculosis to rule out female genital tuberculosis before infertility treatments are initiated.

Impact of menopausal hormone formulations on pituitary-ovarian regulatory feedback.

Changes in pituitary-ovarian hormones across the menopausal transition have multiple physiological consequences. However, little is known about how the major types of postmenopausal hormone therapy (HT) affect pituitary-ovarian hormonal relationships. This study evaluated these relationships in recently menopausal women (52.45 ± 2.49 yr of age) in the Kronos Early Estrogen Prevention Study (KEEPS) who were compliant to randomized, double-blinded treatment with oral conjugated equine estrogen (o-CEE; n = 109), transdermal 17ß-estradiol (t-E2; n = 107), or placebo (n = 146). Androstenedione, testosterone, 17ß-estradiol, estrone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum before (baseline) and 48 mo after randomization to treatment. Descriptive summaries of hormone levels were performed, and multiple regression analyses were used to examine the effects of o-CEE, t-E2, and placebo on these hormone levels at 48 mo, adjusting for baseline levels. A network analysis examined the covariance of changes in hormone levels over the 48 mo within treatment groups. As expected, at 48 mo of treatment, hormone levels differed between women in the two active treatment groups compared with placebo, and network analysis indicated stronger relationships among hormone levels in the t-E2 and o-CEE groups compared with placebo. Associations among testosterone, 17ß-estradiol, FSH, and LH differed between the o-CEE group compared with t-E2 and placebo groups. Thus, two common HT regimens differentially alter pituitary-ovarian hormone levels, altering feedback cycles and interhormonal associations in recently menopausal women. These interactions provide the basis for future studies investigating the impact of hormonal modulation of aging, including cognitive decline in women.

Managing Menopause by Combining Evidence With Clinical Judgment.

Menopause occurring before the age of 40 harbors unique challenges as well as lifetime burden resulting from premature deprivation from ovarian hormones, primarily estrogen. Cessation of ovarian function before age 40 is considered premature (ovarian insufficiency), whereas if occurring before age 45, it is deemed "early." Early/premature menopause may be idiopathic, medically, or surgically induced. Regardless of the cause, for such women, menopausal hormone therapy is truly replacement and should continue until at least the average age of menopause. Hormone therapy offers the benefit of symptom control, and prevention of health consequences associated with premature loss of ovarian hormones.

Predictors of depression in women with polycystic ovary syndrome.

The aim of this study is to assess the prevalence and predictors of depressive symptoms in women with polycystic ovary syndrome (PCOS). In a cross-sectional study of 114 women seeking consultation for symptoms of PCOS (menstrual irregularity, hirsutism, and/or acne), personal and family history of depression (HD and FHD respectively) were enquired. Vitamin D status (n = 104) and manifest depressive symptoms assessed by personal health questionnaire (PHQ) (MD) were evaluated in a subset (85). Relationships between HD and MD with PCOS symptoms, FHD, and vitamin D status were assessed using adjusted analyses. Thirty-five percent acknowledged a HD; MD (PHQ > 4) was apparent in 43 %. HD was associated with hirsutism (OR 2.4, 95 % CI 1.01-5.9), disturbed sleep (OR 3.0, 95 % CI 1.3-6.9), and with FHD (OR 4.8, 95 % CI 1.7-13.5). Disturbed sleep (OR 2.4, 95 % CI 1.01-5.7) and FHD (OR 3.8, 95 % CI 1.3-11.2) were independent predictors of HD adjusting for race and BMI. An inverse correlation was noted between serum 25 OH vitamin D (25OHD) levels and PHQ score, but only in those with vitamin D deficiency (25OHD ≤ 30 ng/ml, n = 57, r =-0.32, p = 0.015). 25OHD < 20 ng/ml (OR 3.5, 95 % CI 1.1-11.8) and HD (OR 12.8, 95 % CI 3.6-45.2) predicted scoring in the highest PHQ tertile after adjusting for hirsutism, BMI, and race. In women with PCOS, disturbed nocturnal sleep and FDH predicted personal HD, whereas HD and vitamin D deficiency related to the severity of MD symptoms.

Blood type predicts live birth in the infertile population.

PURPOSE: To determine if blood type in infertile women relates to the likelihood for live birth (LB) following IVF, and to the etiology for infertility. METHODS: Retrospective study of patients undergoing IVF at two academic centers in the northeast US. Relationships between blood type (A, B, AB, O) and patient characteristics, IVF cycle parameters and LB were assessed utilizing multivariable logistic regression analyses. RESULTS: In the studied population (n=626), women with type O were significantly more likely to have baseline FSH > 10 IU/L after adjusting for age, BMI and race (OR 5.09, 95 % CI 1.4-18.7, p=0.01). Conversely, women with blood type A were significantly more likely to have ovulatory infertility compared to those with blood type O after adjusting for age and BMI (OR 3.2, 95 % CI 1.7-6.2). Blood type B was associated with increased likelihood of live birth (OR 1.9, 95 % CI 1.10-3.41, p=0.03) after adjusting for factors recognized to impact IVF outcome. CONCLUSION: Ovulatory infertility and baseline FSH > 10 IU/L were more prevalent in women with blood type A and O respectively. However, those of blood type B had significantly higher odds for LB compared to other blood types after adjusting for factors recognized to impact on IVF cycle outcome. While underlying mechanisms are unclear, for infertile women, patient's blood type is seemingly relevant for IVF cycle outcome.

Donor egg IVF model to assess ecological implications for ART success.

PURPOSE: Environmental influences on reproductive success are recognized. We hypothesized that location of fertility clinics may influence treatment success and explored this hypothesis utilizing donor egg IVF (IVF) embryo transfer (ET) model. METHODS: Publicly accessible national registry data (Society for Assisted Reproductive Technology) on fresh & frozen (FET) ET cycles undertaken at participating clinics across North America (n = 444 IVF centers) for 2007 were utilized. Information on number of donor egg IVF cycles, live birth (LB) rate following fresh and frozen ET(FET), average number (#) of ET and IVF center's location, geographical coordinates (latitude, longitude, altitude), annualized average temperatures and midyear regional ultraviolet B (UVB) radiation intensity were obtained. Multivariable logistic regression analyses assessed relationship between LBR (in tertile and uppermost versus lesser quartiles) following fresh and FET with geographical coordinates (region and altitude of clinic location) and ecological influences (average temperature and midyear UVB intensity), adjusting for #ET and clinic experience with donor egg IVF. RESULTS: Average number of fresh ET, clinic location (region) and midyear UVB intensity were positive predictors of LBR following fresh ET, whereas altitude and annualized average regional temperature demonstrated an inverse relationship with LBR following fresh ET. For FET cycles, #ET, clinic region and altitude were positive determinants of increasing LBR's. Annualized regional temperature and midyear UVB failed to demonstrate any relationship with LB following donor egg FET. CONCLUSION: Our data suggest that ecological influences may relate to donor egg IVF cycle success. Future studies are needed to better elucidate the mechanisms that could explain the observed associations.

Racial disparities in the outcomes of euploid single frozen-thawed embryo transfer cycles - analysis of the Clinical Outcome Reporting System of the Society for Assisted Reproductive Technology 2016-2018 data.

OBJECTIVE: To evaluate if in pregnancies conceived with the transfer of single genetically tested embryos, maternal race and ethnicity relate to pregnancy outcome. DESIGN: Retrospective cohort. SETTING: Data available in the Clinical Outcome Reporting System of the Society for Assisted Reproductive Technology (SART-CORS) for years 2016-2018. PATIENT(S): Autologous frozen-thaw embryo transfer (FET) cycles with transfer of single genetically tested embryo in SART-CORS for years 2016-2018; cycles associated with diagnoses of recurrent pregnancy loss, gestational carrier, donor egg and donor embryo were excluded. INTERVENTION(S): Information on race and ethnicity linked with in vitro fertilization and FET cycles available in SART-CORS. MAIN OUTCOME MEASURE(S): Multivariable analyses using generalized estimating equation examined the relationship between categories of race and ethnicity with the following outcomes: Pregnancy positive ß hCG (human chorionic gonadotropin), clinical pregnancy, pregnancy loss (early [at gestation <13 weeks] and late [loss between ≥13 and <20 weeks]), preterm (<37 weeks), term (≥37 weeks) and live birth. Covariates adjusted for included age, body mass index, anti-Mullerian hormone, infertility diagnosis and smoking history. RESULT(S): Seventy-nine thousand four hundred and sixteen FET cycles met the eligibility criteria. Information on race and ethnicity was specified for 50,820 (64.0%) and was not known in 28,723 (36%) of the cycles. The population was predominantly non-Hispanic White (44%); non-Hispanic Black comprised 2.7%, Asian 12.3%, Hispanic 3.4%, and American Indian, Pacific Islander, Hawaiian, and Alaskan comprised 0.2% of the population. Nearly 1.0 % self-identified with more than one race. On multivariable analyses, pregnancies in non-Hispanic Black and in Hispanic women (compared with non-Hispanic Whites') were significantly more likely to result in in preterm birth. Compared with non-Hispanic White women, the likelihood of live birth was significantly lower in non-Hispanic Blacks, Asian, Hispanic, American Indian, Pacific Islander, Hawaiian, and Alaskan women. The likelihood for delivery by Cesarean was also disproportionately higher in the non Hispanic Black and, Hispanic women and in those identifying with more than one race (0.023) compared with non-Hispanic White women. CONCLUSION(S): Racial and ethnic differentials are apparent in the outcomes of FET conceived pregnancies resulting from the transfer of single genetically tested embryos.

Chronicling menstrual cycle patterns across the reproductive lifespan with real-world data.

The intricate hormonal and physiological changes of the menstrual cycle can influence health on a daily basis. Although prior studies have helped improve our understanding of the menstrual cycle, they often lack diversity in the populations included, sample size, and the span of reproductive and life stages. This paper aims to describe the dynamic differences in menstrual cycle characteristics and associated symptoms by age in a large global cohort of period-tracking application users. This work aims to contribute to our knowledge and understanding of female physiology at varying stages of reproductive aging. This cohort study included self-reported menstrual cycle and symptom information in a sample of Flo application users aged 18-55. Cycle and period length and their variability, and frequency of menstrual cycle symptom logs are described by the age of the user. Based on data logged by over 19 million global users of the Flo app, the length of the menstrual cycle and period show clear age-associated patterns. With higher age, cycles tend to get shorter (Cycle length: D ¯ = 1.85 days, Cohen's D = 0.59) and more variable (Cycle length SD: D ¯ = 0.42 days, Cohen's D = 0.09), until close to the chronological age (40-44) suggesting menopausal transition, when both cycles and periods become longer (Cycle length: D ¯ = 0.86 days, t = 48.85, Cohen's D = 0.26; Period length: D ¯ = 0.08, t = 15.6, Cohen's D = 0.07) and more variable (Cycle length SD: D ¯ = 2.80 days, t = 111.43, d = 0.51; Period length SD: D ¯ = 0.23 days, t = 67.81, Cohen's D = 0.31). The proportion of individuals with irregular cycles was highest in participants aged 51-55 (44.7%), and lowest in the 36-40 age group (28.3%). The spectrum of common menstrual cycle-related symptoms also varies with age. The frequency of logging of cramps and acne is lower in older participants, while logs of headache, backache, stress, and insomnia are higher in older users. Other symptoms show different patterns, such as breast tenderness and fatigue peaking between the ages of 20-40, or mood swings being most frequently logged in the youngest and oldest users. The menstrual cycle and related symptoms are not static throughout the lifespan. Understanding these age-related differences in cycle characteristics and symptoms is essential in understanding how best to care for and improve the daily experience for menstruators across the reproductive life span.

Cardiometabolic outcomes in Kronos Early Estrogen Prevention Study continuation: 14-year follow-up of a hormone therapy trial.

OBJECTIVE: This study aimed to determine long-term cardiometabolic effects of hormone therapies initiated within 3 years of onset of menopause after a 14-year follow-up study of participants of the Kronos Early Estrogen Prevention Study (KEEPS). METHODS: KEEPS was a multisite clinical trial that recruited recently menopausal women with good cardiovascular health for randomization to oral conjugated equine estrogens (Premarin, 0.45 mg/d) or transdermal 17ß-estradiol (Climara, 50 µg/d) both with micronized progesterone (Prometrium, 200 mg/d) for 12 d/mo, or placebo pills and patch for 4 years. KEEPS continuation recontacted KEEPS participants 14 years after randomization and 10 years after the completion of the 4-year clinical trial to attend in-person clinic visits. RESULTS: Participants of KEEPS continuation (n = 299 of the 727 KEEPS participants; 41%) had an average age of 67 years (range, 58-73 y). Measurements of systolic and diastolic blood pressures, waist-to-hip ratio, fasting levels of glucose, insulin, lipid profiles, and homeostasis model assessment of insulin resistance were not different among the treatment groups at either KEEPS baseline or at KEEPS continuation visits, or for change between these two visits. The frequency of self-reported diabetes ( P = 0.007) and use of diabetes medications was higher in the placebo than the oral conjugated equine estrogens ( P = 0.045) or transdermal 17ß-estradiol ( P = 0.02) groups, but these differences were not supported by the laboratory measurements of glycemia or insulin resistance. CONCLUSIONS: There was no evidence of cardiovascular and/or metabolic benefits or adverse effects associated with 4 years use of oral or transdermal forms of hormone therapy by recently menopausal women with good cardiovascular health after 10 years.

Aberrant endocrinology and ovarian response to clomiphene citrate during the course of an undiagnosed early intrauterine pregnancy: a case report.

BACKGROUND: This is an unusual case of embryonic exposure to clomiphene citrate (CC) in the setting of an undiagnosed early pregnancy with successful follicular response to CC and progression of pregnancy despite markedly attenuated serum progesterone and estradiol levels and a thin endometrium. A review of literature on the potential of CC for teratogenicity is presented. CASE: A 36-year-old woman underwent 2 ovulation inductions (OIs) with CC. Successful pregnancy followed the second OI cycle. Fetal measurements on transvaginal ultrasound identified the pregnancy to be chronologically advanced and consistent with the first OI treatment cycle. The follicular response to CC during the second OI cycle in the setting of ongoing early pregnancy, and pregnancy progression despite markedly attenuated endometrium, low serum levels of serum progesterone, and estradiol and embryonic exposure to CC, are notable. CONCLUSION: The possibility of inadvertent embryonic exposure to fertility drugs in the event of undiagnosed early pregnancy must be considered in infertile patients pursuing repeat treatment cycles. Serum beta-hCG testing should be considered before repeat treatments.