Kapoor, Ekta

Abstract Background Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. Methods We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. Results We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. Conclusions This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.

Abstract Introduction Sexual dysfunction is a common problem in women and the nature of its association with alcohol use remains unclear. Aim To explore the association between alcohol use and female sexual dysfunction (FSD). Methods Associations between self-reported drinking and sexual function were evaluated in 2,253 women presenting for consultation to a women’s health specialty clinic. A short version of the Alcohol Use Disorders Identification Test (AUDIT-C) was used to evaluate alcohol use. Women with an AUDIT-C ≥3 were considered at risk for hazardous drinking. Multivariable regression, controlling for depression, anxiety, and abuse (childhood and recent), was used to assess the association between alcohol consumption and FSD (defined as a Female Sexual Function Index [FSFI] ≤26.55 and Female Sexual Distress Scale [FSDS] ≥11) in sexually active women. Main Outcome Measure The main study outcome measure was the presence of FSD as defined by a score ≤26.55 on the FSFI and ≥11 on the FSDS. Results 57% of the 1,649 sexually active women were classified as having FSD; 80% reported any alcohol use and 38% reported drinking patterns with the potential to be hazardous. The women at risk for hazardous drinking had significantly higher FSFI domain scores indicating better sexual function (P ≤ .001). However, in multivariable analyses, there was no significant difference in the rates of FSD across alcohol use categories in women. Conclusion In women presenting for consultation to a women’s health specialty clinic, an association between alcohol use and FSFI scores was seen, in which greater risk of hazardous drinking was associated with better sexual function scores. However, when sexual distress was included to define sexual dysfunction, those with FSD were not at higher risk of hazardous drinking. Given the complex nature of FSD, additional study is needed to further clarify these relationships.

Abstract BACKGROUND Previously defined thresholds for total testosterone (TT) concentrations to screen for androgen-producing tumors (APTs) have used RIA, which can be less accurate in women. We aimed to define diagnostic thresholds to screen for APTs or postmenopausal pathologic hyperandrogenism using TT concentrations measured by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). METHODS We performed a retrospective cohort study on all women with TT ≥3.5 nmol/L and all postmenopausal women presenting with hyperandrogenism between 2004 and 2014 at the Mayo Clinic in Rochester, MN. RESULTS Of the 369 women with TT ≥3.5 nmol/L, 89 were included and subdivided into 3 groups based on their clinical diagnosis [21 (24%), APT; 16 (18%), postmenopausal pathologic hyperandrogenism; 52 (58%), polycystic ovary syndrome]. The source of the APT was more frequently ovarian (81%, n = 17) than adrenal (19%, n = 4). The diagnostic threshold using ROC analysis for TT to identify APT in women with severe biochemical hyperandrogenemia was ≥5.1 nmol/L (sensitivity, 90%; specificity, 81%). In a second analysis of a cohort of postmenopausal women only presenting with symptoms or signs of hyperandrogenism, median TT was significantly higher in the postmenopausal pathologic hyperandrogenism group (APT and ovarian hyperthecosis) vs the idiopathic hyperandrogenism group (4.9 vs 0.8 nmol/L; P < 0.01). In postmenopausal women, the diagnostic threshold for pathologic hyperandrogenism was TT ≥2.2 nmol/L (sensitivity, 100%; specificity, 86%). CONCLUSIONS The diagnostic threshold for TT concentration as measured by LC-MS/MS to identify APT in women with biochemical severe hyperandrogenemia was TT ≥5.1 nmol/L. In postmenopausal women, the diagnostic threshold for pathologic hyperandrogenism was lower (TT ≥2.2 nmol/L).

Gynecologic cancers are common in the United States and represent a significant health burden. Treatment of these cancers often causes premature cessation of ovarian function, with resultant symptoms that are often more severe than those associated with natural menopause. Hormone therapy is the most effective treatment for menopausal symptoms, but the decision-making process about its use can be complex for survivors of gynecologic cancer. In this review, we provide evidence-based recommendations about the use of hormone therapy after gynecologic cancer.

Abstract Objective: Frequency of vasomotor symptoms (VMS) in older women and the contributing factors are largely undefined. We measured the frequency of moderate-to-severe vasomotor symptoms (msVMS) in women ≥60 years of age and examined their characteristics to determine factors that may associate with VMS in older women. Methods: A cross-sectional survey was completed using the Menopause Health Questionnaire from the Data Registry on Experiences of Aging, Menopause, and Sexuality. Data were collected from women presenting for menopause consultation to Mayo Clinic, Rochester, MN, from January 1, 2006 to October 7, 2014. We created a binary variable where women were classified as having msVMS bother if they reported “quite a bit” or “extremely” compared with women reporting “not at all” or “a little bit.” Women with and without msVMS were evaluated by menopause type, self-rated heath, current tobacco, caffeine, and alcohol use, as well as pertinent medication use. Associations between participant characteristics and msVMS were evaluated using logistic regression and a multivariable model with age as a covariate. Interactions between participant characteristics and age were also assessed. Results: Of the 4,956 women presenting for menopause consultation, 921 (18%) were ≥60 years old. Of these, 379 (41.2%) reported msVMS bother. Women with msVMS were more likely to have a history of nonspontaneous menopause and report their health as fair, versus good or excellent. Women reporting current use of hormone therapy (HT) (21%) were less likely to report msVMS compared with those not taking HT (P < 0.001). Conclusions: A substantial number of women seen in a specialty menopause clinic were over age 60 years and reported msVMS, highlighting that VMS may be disruptive in women over a decade past the natural age of menopause.

Abstract Objective: Response to menopausal hormone therapy (MHT) shows individual variation. SLCO1B1 encodes the OATP1B1 transporter expressed in the liver that transports many endogenous substances, including estrone sulfate, from the blood into hepatocytes. This study evaluated the relationship between genetic variation in SLCO1B1 and response to MHT in women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS) at Mayo Clinic, Rochester, MN. Methods: KEEPS participants were randomized to oral conjugated equine estrogen (n = 33, oCEE), transdermal 17β-estradiol (n = 33, tE2), or placebo (n = 34) for 48 months. Menopausal symptoms (hot flashes, night sweats, insomnia, palpitations) were self-reported before treatment and at 48 months. Estrone (E1), E2, and sulfated conjugates (E1S, E2S) were measured using high-performance liquid chromatography-tandem mass spectrometry. SLCO1B1 rs4149056 (c.521T>C, p.Val174Ala) was genotyped using a TaqMan assay. Results: After adjusting for treatment, there was a significant association between the SLCO1B1 rs4149056 TT genotype (encoding normal function transporter) and lower E1S, E1S/E1, and E2S (P = 0.032, 0.010, and 0.008, respectively) compared with women who were heterozygous (TC) or homozygous (CC) for the reduced function allele. The interactions between genotype, treatment, and E2S concentration were stronger in women assigned to tE2 (P = 0.013) than the women taking oCEE (P = 0.056). Among women assigned to active treatment, women with the CT genotype showed a significantly greater decrease in night sweats (P = 0.041) than those with the TT genotype. Conclusions: Individual variation in sulfated estrogens is explained, in part, by genetic variation in SLCO1B1. Bioavailability of sulfated estrogens may contribute to relief of night sweats.

Abstract Hot flashes have typically been classified as “symptoms of menopause” that should be tolerated or treated until they resolve. However, mounting evidence points to hot flashes as a manifestation of one or several underlying pathophysiological processes. Associations exist between the presence, timing of onset, severity, and duration of hot flashes, and the risk of several neurological (affecting sleep, mood, and cognition) and cardiovascular conditions. In addition, four consistent patterns of vasomotor disturbances have been identified across different countries, making it unlikely that these patterns are solely explained by socioeconomic or cultural factors. The changing hormonal environment of menopause may unmask differences in the autonomic neurovascular control mechanisms that put an individual woman at risk for chronic conditions of aging. These differences may have a genetic basis or may be acquired across the life span and are consistent with the variability of the clinical manifestations of aging observed in women after bilateral oophorectomy. It is time to investigate the pathophysiological mechanisms underlying the four patterns of vasomotor symptoms more closely, and to shift from describing hot flashes as symptoms to be tolerated to manifestations of an underlying autonomic neurovascular dysregulation that need to be addressed.