Carolyn J. Gibson

Pharmacologically Induced Hypogonadism and Sexual Function in Healthy Young Women and Men

Studies fail to find uniform effects of age-related or induced hypogonadism on human sexual function. We examined the effects of induced hypogonadism on sexual function in healthy men and women and attempted to identify predictors of the sexual response to induced hypogonadism or hormone addback. The study design used was a double-blind, controlled, crossover (self-as-own control). The study setting was an ambulatory care clinic in a research hospital, and the participants were 20 men (average±SD age=28.5±6.2 years) and 20 women (average±SD age=33.5±8.7 years), all healthy and with no history of psychiatric illness. A multidimensional scale assessing several domains of sexual function was the main outcome measure. Participants of the study received depot leuprolide acetate (Lupron) every 4 weeks for 3 months (men) or 5 months (women). After the first month of Lupron alone, men received (in addition to Lupron) testosterone enanthate (200 mg intramuscularly) or placebo every 2 weeks for 1 month each. Women received Lupron alone for 2 months, and then, in addition to Lupron, they received estradiol and progesterone for 5 weeks each. The results of the study: in women, hypogonadism resulted in a significant decrease in global measures of sexual functioning, principally reflecting a significant decrease in the reported quality of orgasm. In men, hypogonadism resulted in significant reductions in all measured domains of sexual function. Testosterone restored sexual functioning scores in men to those seen at baseline, whereas neither estradiol nor progesterone significantly improved the reduced sexual functioning associated with hypogonadism in women. Induced hypogonadism decreased sexual function in a similar number of men and women. No predictors of response were identified except for levels of sexual function at baseline. In conclusion, our data do not support a simple deficiency model for the role of gonadal steroids in human sexual function; moreover, while variable, the role of testosterone in sexual function in men is more apparent than that of estradiol or progesterone in women.

Changes in Cardiovascular Risk Factors by Hysterectomy Status with and without Oophorectomy: Study of Women’s Health across the Nation

OBJECTIVES The aim of this study was to compare the changes in risk factors for cardiovascular disease (CVD) leading up to and after hysterectomy with or without bilateral oophorectomy with the changes observed up to and after natural menopause. BACKGROUND Evidence suggests that hysterectomy status with or without bilateral oophorectomy might increase risk for CVD, but most studies retrospectively assess menopausal status. METHODS Study of Womens Health across the Nation enrolled 3,302 pre-menopausal women not using hormone therapy between 42 and 52 years of age and followed them annually for over 11 years for sociodemographic characteristics, menopausal status, surgeries, body mass index, medication use, lifestyle factors, lipids, blood pressure, insulin resistance, and hemostatic and inflammatory factors. By 2008, 1,769 women had reached natural menopause, 77 women had a hysterectomy with ovarian conservation, and 106 women had a hysterectomy with bilateral oophorectomy. Piece-wise hierarchical growth models compared these groups on annual changes in CVD risk factors before and after final menstrual period or surgery. RESULTS Multivariable analyses showed that annual changes in CVD risk factors did not vary by group, with few exceptions, and the significant group differences that did emerge were not in the anticipated direction. CONCLUSIONS Hysterectomy with or without ovarian conservation is not a key determinant of CVD risk factor status either before or after elective surgery in midlife. These results should provide reassurance to women and their clinicians that hysterectomy in midlife is unlikely to accelerate the CVD risk of women.

Negative affect and vasomotor symptoms in the Study of Women's Health Across the Nation Daily Hormone Study.

ObjectiveVasomotor symptoms (VMS) are common during the menopausal transition. Negative affect is consistently associated with self-reported VMS, but the interpretation of this relationship is limited by the infrequent measurement and retrospective recall of VMS. Using prospective data from daily diaries, we examined the daily association between negative affect and reported VMS, as well as the temporal associations between negative affect and next-day VMS and between VMS and next-day negative affect. MethodsData were derived from the third wave of the Daily Hormone Study (N = 625). The Daily Hormone Study is a substudy of the Study of Women’s Health Across the Nation, a multisite community-based prospective cohort study of the menopausal transition. Participants reported VMS and affect in daily diaries for 12 to 50 days. Multilevel mixed models were used to determine the associations between reported VMS and negative affect, adjusted by antidepressant use, age, education, menopause status, self-reported health, and race/ethnicity, drawn from annual Study of Women’s Health Across the Nation visits. ResultsVMS were reported by 327 women (52.3%). Negative affect was positively associated with VMS (odds ratio [OR], 1.76; 95% CI, 1.43-2.17; P < 0.001) in cross-sectional analyses. Negative affect, adjusted by same-day VMS, was not predictive of next-day VMS (OR, 1.11; 95% CI, 0.85-1.35; P = 0.55), whereas VMS, adjusted by same-day negative affect, was predictive of negative affect for the next day (OR, 1.27; 95% CI, 1.03-1.58; P = 0.01). ConclusionsNegative affect is more likely to be reported on the same day and the day after VMS. Potential mechanisms underlying this relationship include negative cognitive appraisal, sleep disruption, and unmeasured third factors.

Mood symptoms after natural menopause and hysterectomy with and without bilateral oophorectomy among women in midlife.

OBJECTIVE: To examine whether mood symptoms increased more for women in the years after hysterectomy with or without bilateral oophorectomy relative to natural menopause. METHODS: Using data from the Study of Womens Health Across the Nation (n=1,970), depression and anxiety symptoms were assessed annually for up to 10 years with the Center for Epidemiological Studies Depression Index and four anxiety questions, respectively. Piece-wise hierarchical growth models were used to relate natural menopause, hysterectomy with ovarian conservation, and hysterectomy with bilateral oophorectomy to trajectories of mood symptoms before and after the final menstrual period or surgery. Covariates included educational attainment, race, menopausal status, age the year before final menstrual period or surgery, and time-varying body mass index, self-rated health, hormone therapy, and antidepressant use. RESULTS: By the tenth annual visit, 1,793 (90.9%) women reached natural menopause, 76 (3.9%) reported hysterectomy with ovarian conservation, and 101 (5.2%) reported hysterectomy with bilateral oophorectomy. For all women, depressive and anxiety symptoms decreased in the years after final menstrual period or surgery. These trajectories did not significantly differ by hysterectomy or oophorectomy status. The Center for Epidemiological Studies Depression Index means were 0.72 standard deviations lower and anxiety symptoms were 0.67 standard deviations lower 5 years after final menstrual period or surgery. CONCLUSION: In this study, mood symptoms continued to improve after the final menstrual period or hysterectomy for all women. Women who undergo a hysterectomy with or without bilateral oophorectomy in midlife do not experience more negative mood symptoms in the years after surgery. LEVEL OF EVIDENCE: II

Body Mass Index Following Natural Menopause and Hysterectomy with and without Bilateral Oophorectomy

Objective:The directional and temporal nature of relationships between overweight and obesity and hysterectomy with or without oophorectomy is not well understood. Overweight and obesity may be both a risk factor for the indications for these surgeries and a possible consequence of the procedure. We used prospective data to examine whether body mass index (BMI) increased more following hysterectomy with and without bilateral oophorectomy compared with natural menopause among middle-aged women.Methods:BMI was assessed annually for up to 10 years in the Study of Women’s Health Across the Nation (SWAN (n=1962)). Piecewise linear mixed growth models were used to examine changes in BMI before and after natural menopause, hysterectomy with ovarian conservation and hysterectomy with bilateral oophorectomy. Covariates included education, race/ethnicity, menopausal status, physical activity, self-rated health, hormone therapy use, antidepressant use, age and visit before the final menstrual period (FMP; for natural menopause) or surgery (for hysterectomy/oophorectomy).Results:By visit 10, 1780 (90.6%) women reached natural menopause, 106 (5.5%) reported hysterectomy with bilateral oophorectomy and 76 (3.9%) reported hysterectomy with ovarian conservation. In fully adjusted models, BMI increased for all women from baseline to FMP or surgery (annual rate of change=0.19 kg m−2 per year), with no significant differences in BMI change between groups. BMI also increased for all women following FMP, but increased more rapidly in women following hysterectomy with bilateral oophorectomy (annual rate of change=0.21 kg m−2 per year) as compared with following natural menopause (annual rate of change=0.08 kg m−2 per year, P=0.03).Conclusion:In this prospective examination, hysterectomy with bilateral oophorectomy was associated with greater increases in BMI in the years following surgery than following hysterectomy with ovarian conservation or natural menopause. This suggests that accelerated weight gain follows bilateral oophorectomy among women in midlife, which may increase risk for obesity-related chronic diseases.

Cognitive performance in healthy women during induced hypogonadism and ovarian steroid addback

Gynecology clinic-based studies have consistently demonstrated that induced hypogonadism is accompanied by a decline in cognitive test performance. However, a recent study in healthy asymptomatic controls observed that neither induced hypogonadism nor estradiol replacement influenced cognitive performance. Thus, the effects of induced hypogonadism on cognition might not be uniformly experienced across individual women. Moreover, discrepancies in the effects of hypogonadism on cognition also could suggest the existence of specific risk phenotypes that predict a woman’s symptomatic experience during menopause. In this study, we examined the effects of induced hypogonadism and ovarian steroid replacement on cognitive performance in healthy premenopausal women. Ovarian suppression was induced with a GnRH agonist (Lupron) and then physiologic levels of estradiol and progesterone were reintroduced in 23 women. Cognitive tests were administered during each hormone condition. To evaluate possible practice effects arising during repeated testing, an identical battery of tests was administered at the same time intervals in 11 untreated women. With the exception of an improved performance on mental rotation during estradiol, we observed no significant effects of estradiol or progesterone on measures of attention, concentration, or memory compared with hypogonadism. In contrast to studies in which a decline in cognitive performance was observed in women receiving ovarian suppression therapy for an underlying gynecologic condition, we confirm a prior report demonstrating that short-term changes in gonadal steroids have a limited effect on cognition in young, healthy women. Differences in the clinical characteristics of the women receiving GnRH agonists could predict a risk for ovarian steroid-related changes in cognitive performance during induced, and possibly, natural menopause.

Daily physical activity and hot flashes in the Study of Women's Health Across the Nation (SWAN) Flashes Study

OBJECTIVE To examine the role of physical activity in menopausal hot flashes. DESIGN Physiologic hot flash monitor and activity monitor over two 48-hour periods, with self-report in an electronic diary. SETTING Community. PATIENT(S) 51 midlife women. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Physiologically detected hot flashes and reported hot flashes with and without physiologic corroboration. RESULT(S) Competing models conceptualize physical activity as a risk or protective factor for hot flashes, but few studies have examined this relationship prospectively using physiologic measures of hot flashes and physical activity. When physiologic hot flashes, reported hot flashes, and reported hot flashes without physiologic corroboration were related to activity changes using hierarchic generalized linear modeling, adjusting for potential confounders, hot flash reports without physiologic corroboration were more likely after activity increases, particularly among women with higher levels of depressive symptoms. No other types of hot flashes were related to physical activity. CONCLUSION(S) Acute increases in physical activity were associated with increased reporting of hot flashes that lacked physiologic corroboration, particularly among women with depressive symptoms. Clinicians should consider the role of symptom perception and reporting in relations between physical activity and hot flashes.

Cortisol dysregulation is associated with daily diary‐reported hot flashes among midlife women

Hot flashes are reported by 70–80% of women during the menopause transition. It has been proposed that cortisol dysregulation is involved in hot flashes, but the relationship between cortisol and hot flashes has received little empirical attention. This study examined the relationship between cortisol and daily self‐reported hot flashes.

Negative attitudes and affect do not predict elective hysterectomy: A prospective analysis from the Study of Women's Health Across the Nation

Objective: Cross-sectional studies suggest an association between hysterectomy and negative affect. Using prospective data, we examined the associations of negative affect, attitudes toward aging and menopause, premenstrual symptoms, and vasomotor symptoms with elective hysterectomy in midlife. Methods: Data were from the Study of Womens Health Across the Nation, a multisite, community-based prospective cohort study of the menopausal transition (n = 2,818). Annually reported hysterectomy at visits 2 to 9 was verified with medical records when available (71%). Anxiety, perceived stress, depressive symptoms, attitudes toward aging and menopause, vasomotor symptoms, and premenstrual symptoms were assessed at baseline using standardized questions. Cox proportional hazards models were used to relate these variables to subsequent elective hysterectomy. Covariates included demographic variables, menstrual bleeding problems, body mass index, hormone levels, and self-rated health, also assessed at baseline. Results: Elective hysterectomy was reported by 6% (n = 168) of participants over an 8-year period. Women with hysterectomy were not higher in negative affect or negative attitudes toward aging and menopause compared with women without hysterectomy. Vasomotor symptoms (hazard ratio [HR], 1.44; 95% CI, 1.03-2.01; P = 0.03) and positive attitudes toward aging and menopause (HR, 1.74; 95% CI, 1.04-2.93) at baseline predicted hysterectomy over the 8-year period, controlling for menstrual bleeding problems, site, race/ethnicity, follicle-stimulating hormone, age, education, body mass index, and self-rated health. Menstrual bleeding problems at baseline were the strongest predictor of hysterectomy (HR, 4.30; 95% CI, 2.05-9.05). Conclusions: In this prospective examination, negative affect and attitudes were not associated with subsequent hysterectomy. Menstrual bleeding problems were the major determinant of elective hysterectomy.

Sexual Assault, Sexual Harassment, and Physical Victimization during Military Service across Age Cohorts of Women Veterans

OBJECTIVES Exposure to sexual and physical trauma during military service is associated with adverse mental and physical health outcomes. Little is known about their prevalence and impact in women veterans across age cohorts. METHODS Data from a 2013 national online survey of women veterans was used to examine associations between age and trauma during military service, including sexual assault, sexual harassment, and physical victimization. Analyses were conducted using logistic regression, adjusting for service duration and demographic factors. In secondary analyses, the moderating role of age in the relationship between trauma and self-reported health was examined. RESULTS The sample included 781 women veterans. Compared with the oldest age group (≥ 65), all except the youngest age group had consistently higher odds of reporting trauma during military service. These differences were most pronounced in women aged 45 to 54 years (sexual assault odds ratio [OR], 3.81 [95% CI, 2.77-6.71]; sexual harassment, OR, 3.99 [95% CI, 2.25-7.08]; and physical victimization, OR, 5.72 [95% CI, 3.32-9.85]). The association between trauma during military service and self-reported health status also varied by age group, with the strongest negative impact observed among women aged 45 to 54 and 55 to 64. CONCLUSIONS Compared with other age groups, women in midlife were the most likely to report trauma during military service, and these experiences were associated with greater negative impact on their self-reported health. Providers should be aware that trauma during military service may be particularly problematic for the cohort of women currently in midlife, who represent the largest proportion of women who use Department of Veterans Affairs health care.