Ekta Kapoor

ACTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-Analysis

CONTEXT The diagnosis of adrenal insufficiency is clinically challenging and often requires ACTH stimulation tests. OBJECTIVE To determine the diagnostic accuracy of the high- (250 mcg) and low- (1 mcg) dose ACTH stimulation tests in the diagnosis of adrenal insufficiency. METHODS We searched six databases through February 2014. Pairs of independent reviewers selected studies and appraised the risk of bias. Diagnostic association measures were pooled across studies using a bivariate model. DATA SYNTHESIS For secondary adrenal insufficiency, we included 30 studies enrolling 1209 adults and 228 children. High- and low-dose ACTH stimulation tests had similar diagnostic accuracy in adults and children using different peak serum cortisol cutoffs. In general, both tests had low sensitivity and high specificity resulting in reasonable likelihood ratios for a positive test (adults: high dose, 9.1; low dose, 5.9; children: high dose, 43.5; low dose, 7.7), but a fairly suboptimal likelihood ratio for a negative test (adults: high dose, 0.39; low dose, 0.19; children: high dose, 0.65; low dose, 0.34). For primary adrenal insufficiency, we included five studies enrolling 100 patients. Data were only available to estimate the sensitivity of high dose ACTH stimulation test (92%; 95% confidence interval, 81-97%). CONCLUSION Both high- and low-dose ACTH stimulation tests had similar diagnostic accuracy. Both tests are adequate to rule in, but not rule out, secondary adrenal insufficiency. Our confidence in these estimates is low to moderate because of the likely risk of bias, heterogeneity, and imprecision.

The association between recent abuse and menopausal symptom bother: results from the Data Registry on Experiences of Aging, Menopause, and Sexuality (DREAMS).

Objective:The aim of the study was to determine whether there is an association between current menopausal symptom bother and a history of abuse (physical, sexual, or emotional/verbal) in the last year. Methods:A cross-sectional survey was completed using the Data Registry on Experiences of Aging, Menopause, and Sexuality and the Menopause Health Questionnaire. Data from the Menopause Health Questionnaire were collected from 4,956 women seen consecutively for menopause consultation in the Womens Health Clinic at Mayo Clinic (Rochester, MN) from January 1, 2006 through October 7, 2014. Data from 3,740 women were included in the analysis. Menopausal symptom ratings were compared between women reporting a history of abuse (physical, sexual, or emotional/verbal) in the last year and those not using a two-sample t test. Analysis of covariance was used to assess whether abuse was associated with menopausal symptom bother after adjusting for baseline participant characteristics. Results:Of the 3,740 women, 253 (6.8%) reported experiencing one or more forms of abuse in the last year, the majority (96%) of which was verbal/emotional abuse. Those reporting abuse in the last year had higher (P < 0.001) mean total menopausal symptom bother scores. Consistent findings were obtained from multivariable analyses adjusting for all demographic and substance use characteristics. Conclusions:In the present study from the Data Registry on Experiences of Aging, Menopause, and Sexuality, menopausal symptom bother scores were directly associated with recent self-reported abuse.

Genitourinary Syndrome of Menopause: Management Strategies for the Clinician

&NA; Genitourinary syndrome of menopause (GSM), previously known as atrophic vaginitis or vulvovaginal atrophy, affects more than half of postmenopausal women. Caused by low estrogen levels after menopause, it results in bothersome symptoms, including vaginal dryness, itching, dyspareunia, urinary urgency and increased frequency, and urinary tract infections. Even though women with GSM can have sexual dysfunction that interferes with partner relationships, women are often embarrassed to seek treatment, and health care professionals do not always actively screen for GSM. As a result, GSM remains underdiagnosed and undertreated. Several effective treatments exist, but low‐dose vaginal estrogen therapy is the criterion standard. It is effective and safe for most patients, but caution is suggested for survivors of hormone‐sensitive cancers. Newer treatment options include selective estrogen receptor modulators, vaginal dehydroepiandrosterone, and laser therapy. Nonprescription treatments include vaginal lubricants, moisturizers, and dilators. Pelvic floor physical therapy may be indicated for some women with concomitant pelvic floor muscle dysfunction. Sex therapy may be helpful for women with sexual dysfunction. This concise review presents a practical approach to the evaluation and management of GSM for the primary care physician. Abbreviations and Acronyms: AI = aromatase inhibitor; DHEA = dehydroepiandrosterone; ET = estrogen therapy; FDA = US Food and Drug Administration; GSM = genitourinary syndrome of menopause; SERM = selective estrogen receptor modulator

Menopausal hormone therapy in cancer survivors: A narrative review of the literature

Decision making regarding the use of menopausal hormone therapy (MHT) for the treatment of bothersome menopausal symptoms in a cancer survivor can be complex, and includes assessment of its impact on disease-free or overall survival. Estrogen receptors are present in several cancer types, but this does not always result in estrogen-mediated tumor proliferation and adverse cancer-related outcomes. Estrogen may even be protective against certain cancers. Menopausal hormone therapy is associated with an increased risk of recurrence and mortality after diagnosis of some cancer types, but not others. We provide a narrative review of the medical literature regarding the risk of cancer recurrence and associated mortality with initiation of MHT after the diagnosis of breast, gynecologic, lung, colorectal, hematologic cancers, and melanoma. Menopausal hormone therapy may be considered for management of bothersome menopausal symptoms in women with some cancer types (e.g., colorectal and hematologic cancer, localized melanoma, and most cervical, vulvar and vaginal cancers), while nonhormonal treatment options may be preferred for others (e.g., breast cancer). In women with other cancer types, recommendations are less straightforward, and the use of MHT must be individualized.

A negative view of menopause: does the type of symptom matter?

Abstract Objectives: To assess the association between the type of symptom and women’s self-reported view of menopause. Methods: The study was conducted at Mayo Clinic, Rochester MN, between January 2006 and October 2014. Women aged 40–64 were included. Data from 1420 women were analyzed in a cross-sectional design. The Menopause Health Questionnaire was used for symptom assessment. Odds ratios (ORs) and population attributable risk (PAR) (OR × percent frequency) were calculated for each symptom. Logistic regression analyses were performed with the view of menopause as the dependent variable. Results: Anxiety (2.34), depressed mood (2.24), irritability (2.22), vaginal itching (2.27), crying spells (2.1) and breast tenderness (2.08) were associated with highest odds of having a negative view of menopause. Highest PAR (population impact) symptoms were anxiety (22.27), weight gain (20.66), fatigue (20.28) and irritability (19.41). Hot flushes and night sweats, although common, were not associated with a negative view of menopause (OR 1.3 and 1.16; PAR 3.85 and 4.42, respectively). Conclusion: Mood symptoms, vaginal itching, weight gain, breast tenderness and fatigue, although less common than hot flushes, were noted to have greater association with a negative view of menopause. Specifically addressing these symptoms during menopausal consultation may improve patient satisfaction and outcomes.

Association of vasomotor symptoms and sleep apnea risk in midlife women

Objective: The aim of the study was to determine the association between self-reported vasomotor symptoms (VMS) and obstructive sleep apnea (OSA) risk. Methods: The STOP-BANG to evaluate OSA and Menopause Rating Scale (MRS) were administered to 2,935 women seen in the Womens Health Clinic at Mayo Clinic in Rochester, MN, between May 2015 and December 2016. Of these, 1,691 women were included in the analysis. Total MRS and VMS ratings were compared using logistic regression, with age, smoking, and body mass index (BMI) included as covariates between women at intermediate/high risk versus low risk for OSA. Results: Total MRS scores were significantly higher in women with intermediate/high-risk OSA scores versus those with low-risk scores [mean (SD): 16.8 (8.0) vs 12.9 (7.0), P < 0.001]. Women at intermediate/high OSA risk were older, had more education, self-reported hypertension, BMI >35 kg/m2, and were less likely to be married or employed. Self-reported severe/very severe VMS were significantly associated with intermediate/high risk versus low risk for OSA (26.6% vs 15.0%; P < 0.001). After adjusting for age, BMI, smoking status, and self-reported hypertension, the odds of having intermediate/high risk for OSA were 1.87 times higher for those with severe/very severe VMS compared with those with none/mild/moderate VMS (95% CI, 1.29-2.71, P < 0.001). This association persisted upon subgroup analysis based on BMI <25 kg/m2 (odds ratio 2.15; 95% CI, 1.12-4.16, P = 0.022). Conclusions: Self-reported severe/very severe VMS were associated with intermediate/high risk for OSA in midlife women, even in women with BMI <25 kg/m2. Given the limitations of the STOP-BANG tool, OSA risk may, however, have been overestimated.

GLUCOCORTICOID REPLACEMENT REGIMENS IN CHRONIC ADRENAL INSUFFICIENCY: A SYSTEMATIC REVIEW AND META-ANALYSIS

OBJECTIVE Various glucocorticoid (GC) regimens have been used in the treatment of patients with adrenal insufficiency, yet the differences between such regimens on health outcomes are unclear. We performed a systematic review and meta-analysis to compare the effects of GC regimens on quality of life (QoL), bone density, incidence of adrenal crisis, and death. In pediatric studies, we also searched for final adult height. METHODS We searched 6 databases through July 2016. Studies were selected and appraised by independent reviewers. Data were pooled using the profile likelihood random-effects model. RESULTS We included 34 studies. We found no difference in QoL scores between higher (≥30 mg/day of hydrocortisone [HC] equivalence) vs. lower daily doses (<30 mg/day of HC equivalence) (P = .15) or based on frequency of daily dosing (once, twice or thrice daily). Extended-release (1 study), dual-/modified-release (3 studies), and continuous subcutaneous (3 studies) forms of GCs were associated with higher QoL scores. There was no significant association between dose and type of GC and the incidence of adrenal crises. The effect on bone mineral density was heterogeneous. No data were available on mortality or final adult height in children. The quality of evidence was low due to increased risk of bias, imprecision, and heterogeneity. CONCLUSION Extended-/dual-release, and continuous subcutaneous forms of GC may be associated with higher QoL scores. However, this is derived from short-term and imprecise evidence, warranting low confidence. ABBREVIATIONS AI = adrenal insufficiency BMD = bone mineral density GC = glucocorticoids HC = hydrocortisone QoL = quality of life RCT = randomized controlled trial.

Personal Perspective: What's in a name: Are menopausal "hot flashes" a symptom of menopause or a manifestation of neurovascular dysregulation?

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.

Weight Gain in Women at Midlife: A Concise Review of the Pathophysiology and Strategies for Management

Abstract Weight gain accompanied by an increased tendency for central fat distribution is common among women in midlife. These changes are a result of aging, decreasing estrogen levels after menopause, and other unique influences in menopausal women that interfere with the adoption of healthy lifestyle measures. Central obesity, in particular, results in several adverse metabolic consequences, including dysglycemia, dyslipidemia, hypertension, and cardiovascular disease. Given that cardiovascular disease is the leading cause of death in postmenopausal women, the importance of weight management in midlife cannot be overemphasized. In addition, weight gain in midlife contributes to other health risks including cancer, arthritis, mood disorders, and sexual dysfunction. It is imperative that primary care physicians screen midlife women for overweight/obesity and offer appropriate advice and referral. In addition to counseling regarding lifestyle change, behavioral modification, and psychological support, it is important to address the unique barriers to adoption of healthy lifestyle measures in postmenopausal women, including the presence of vasomotor symptoms, mood disorders, and sleep disturbance. When indicated, menopausal hormone therapy should be considered to manage bothersome symptoms. Despite its favorable influence on body fat distribution, menopausal hormone therapy cannot be recommended as a treatment for central obesity in midlife women.

Recommendations for hormone therapy in hysterectomized women: importance of new data in clinical management

Women with a prior hysterectomy with and without oophorectomy represent special cohorts among those who require menopausal hormone therapy (HT), as a progestogen is not required for endometrial protection. This is relevant in light of recent research demonstrating superiority of estrogen therapy alone compared with estrogen plus a progestogen with respect to breast cancer risk and perhaps even cardiovascular protection. No longer is it appropriate to lump all HT regimens together when advising patients. Unfortunately, there is a general reluctance in the healthcare community to prescribe HT even a decade after publication of the results of the Women’s Health Initiative trial. However, with subsequent research showing a favorable benefit/risk balance of short-term estrogen therapy in symptomatic, recently menopausal women, especially those who have undergone hysterectomy with oophorectomy, the need for educating patients and providers on the matter cannot be overemphasized.