Postmenopausal hormone treatment alters neural pathways but does not improve verbal cognitive function.

OBJECTIVE: Cognitive outcomes in trials of postmenopausal hormone treatment have been inconsistent. Differing outcomes may be attributed to hormone formulation, treatment duration and timing, and differential cognitive domain effects. We previously demonstrated treatment benefits on visual cognitive function. In the present study, we describe the effects of hormone treatment on verbal outcomes in the same women, seeking to understand the effects of prior versus current hormone treatment on verbal function. METHODS: This is a cross-sectional evaluation of 57 women (38 hormone users [25 prior long-term users and 13 current users] and 19 never-users). Hormone users took identical formulations of estrogen or estrogen + progestin (0.625 mg/d conjugated equine estrogens with or without medroxyprogesterone acetate) for at least 10 years, beginning within 2 years of menopause. Women were evaluated with tests of verbal function and functional magnetic resonance imaging (fMRI) of a verbal discrimination task. RESULTS: All women scored similarly on assessments of verbal function (Hopkins Verbal Learning Test and a verbal discrimination task performed during the fMRI scanning session); however, women ever treated with hormones had more left inferior frontal (T = 3.72; P < 0.001) and right prefrontal cortex (T = 3.53; P < 0.001) activation during the verbal task. Hormone-treated women performed slightly worse on the verbal discrimination task (mean accuracy 81.72 ±â€Š11.57 ever-treated, 85.30 ±â€Š5.87 never-treated, P = 0.14), took longer to respond (mean reaction time 1.10 ±â€Š0.17 s ever-treated, 1.02 ±â€Š0.11 never-treated, P = 0.03), and remembered fewer previously viewed words (mean accuracy 62.21 ±â€Š8.73 ever-treated, 65.45 ±â€Š7.49 never-treated, P = 0.18). Increased posterior cingulate activity was associated with longer response times (R = 0.323, P = 0.015) and worse delayed verbal recall (R = -0.328, P = 0.048), suggesting that increased activation was associated with less efficient cognitive processing. We did not detect between group differences in activation in the left prefrontal cortex, superior frontal cortex, thalamus, or occipital/parietal junction. CONCLUSIONS: Although current and past hormone treatment was associated with differences in neural pathways used during verbal discrimination, verbal function was not higher than never-users.

Postmenopausal Symptoms in Female Veterans with Type 2 Diabetes: Glucose Control and Symptom Severity.

BACKGROUND: While type 2 diabetes mellitus (DM) is a common condition of midlife women, few studies have examined its influence on the symptom features of menopause. To explore this relationship, we conducted a study of symptom patterns of diabetic patients using a random sample of female veterans receiving care in the Veterans Affairs Healthcare system. METHODS: A cross-sectional comparison was conducted with three groups of postmenopausal respondents (ages 45-60 years) to a mailed national survey who also consented to clinical data access: no diabetes (n=90), diabetes with better glucose control (hemoglobin A1c [HbA1c]≤7%, n=135) and diabetes with worse glucose control (HbA1c>7%, n=102). RESULTS: Respondents, on average, were obese (body mass index: 33.9±0.4 kg/m(2)), 11.30±0.2 years postmenopause, with more than one chronic illness. Despite higher body mass index and increased comorbidities in women with diabetes compared with nondiabetic women, measures of mental health (anxiety, depressed mood, stress) were similar across groups. The pattern of menopause symptoms did not differ by group. Muscle aches/joint pain was the most prevalent symptom (78.6%), followed by vasomotor symptoms (74.4%). Respondents with elevated HbA1c demonstrated higher total menopausal symptom severity scores (DM-HbA1c>7: 15.4±0.8 vs. DM-HbA1c≤7%: 12.2±0.8 vs. No diabetes: 12.3±0.8; p=0.006) than the other two groups. CONCLUSIONS: In postmenopausal female veterans with diabetes, glucose control is associated with the severity of those symptoms commonly attributed to menopause. Joint pain is an important part of the postmenopausal symptom complex in this population.

Differential Contributions of Polycystic Ovary Syndrome (PCOS) Manifestations to Psychological Symptoms.

The purpose of this study was to investigate the relative contributions of previously identified Polycystic ovary syndrome (PCOS) manifestations (infertility, hirsutism, obesity, menstrual problems) to multiple psychological symptoms. Participants were 126 female endocrinology patient volunteers diagnosed with PCOS who completed a cross-sectional study of PCOS manifestations and psychological symptoms. Participants had significantly elevated scores on nine subscales of psychological symptoms. Menstrual problems were significantly associated with all symptom subscales as well as the global indicator, while hirsutism and obesity were significantly related to five or more subscales. After controlling for demographic factors, menstrual problems were the strongest predictor of psychological symptoms. Findings suggest features of excess body hair, obesity, and menstrual abnormalities carry unique risks for adverse psychologic symptoms, but menstrual problems may be the most salient of these features and deserve particular attention as a marker for psychological risk among women with PCOS.

Adipokine concentrations in nonobese women: a study of reproductive aging, body mass index, and menstrual cycle effects.

OBJECTIVE: To explore the influence of reproductive aging, body mass index (BMI), and the menstrual cycle on adiponectin (AD) and leptin concentrations. DESIGN: Cross-sectional comparison in age- and BMI-matched nonobese volunteers with regular cycles (CO, n = 19) or in early postmenopause (EPM, n = 19), aged 40-52 years, and a young cycling group (CY, n = 21), aged 20-30 years. MEASURES: Sex steroids, fasting AD, leptin, insulin, glucose, AD/leptin (A/L) ratio, and insulin resistance (IR) by homeostasis model assessment (HOMA-IR). In ovulatory women, AD, estradiol (E(2)), and progesterone were assessed weekly across the same menstrual cycle. RESULTS: Insulin, glucose, HOMA-IR, A/L ratio, and leptin values were similar across the three study groups. AD differed, with the highest concentrations in the EPM group (CY: 13.0 +/- 0.9 microg/ml vs. CO: 14.0 +/- 1.1 microg/ml vs. EPM: 17.7 +/- 1.5 microg/ml; p = .05). Values among cycling women were similar. When the cycling groups were combined into a premenopausal (PRE) group and compared to EPM women by BMI (> or

Black cohosh has central opioid activity in postmenopausal women: evidence from naloxone blockade and positron emission tomography neuroimaging.

OBJECTIVE: To test whether black cohosh (BC) exhibits an action on the central endogenous opioid system in postmenopausal women. DESIGN: This was a mechanistic study conducted in the same individuals of luteinizing hormone pulsatility with a saline/naloxone challenge (n = 6) and positron emission tomography with [C]carfentanil, a selective micro-opioid receptor radioligand (n = 5), before and after 12 weeks of unblinded treatment with a popular BC daily supplement. RESULTS: BC treatment for 12 weeks at a standard dose (Remifemin, 40 mg/day) had no effect on spontaneous luteinizing hormone pulsatility or estrogen concentrations. With naloxone blockade, there was an unexpected suppression of mean luteinizing hormone pulse frequency (saline vs naloxone = 9.0 +/- 0.6 vs 6.0 +/- 0.7 pulses/16 h; P = 0.056), especially during sleep when the mean interpulse interval was prolonged by approximately 90 minutes (saline night interpulse interval = 103 +/- 9 min vs naloxone night interpulse interval = 191 +/- 31 min, P = 0.03). There were significant increases in mu-opioid receptor binding potential in the posterior and subgenual cingulate, temporal and orbitofrontal cortex, thalamus, and nucleus accumbens ranging from 10% to 61% across brain regions involved in emotional and cognitive function. In contrast, binding potential reductions of lesser magnitude were observed in regions known to be involved in the placebo response (anterior cingulate and anterior insular cortex). CONCLUSIONS: Using two different challenge paradigms for the examination of central opioid function, a neuropharmacologic action of BC treatment was demonstrated in postmenopausal women.

Differential effects of aging on activin A and its binding protein, follistatin, across the menopause transition.

To assess the involvement of ovarian-derived regulatory proteins in FSH modulation, we compared FSH, inhibin A, inhibin B, activin A, and follistatin (FS) in 79 women from the following five groups: young cycling, older cycling, perimenopause (PERI), spontaneous menopause (PM), and surgical menopause receiving estrogen (OVX+ET). Although inhibin B varied as expected by ovarian function, no group differences were observed in activin A, barring a tendency for an increase in PERI, while FS 288 was lower in the PERI, PM, and OVX+ET groups and negatively correlated with advancing age.

Differential associations for menopause and age in measures of vitamin K, osteocalcin, and bone density: a cross-sectional exploratory study in healthy volunteers.

OBJECTIVE: To distinguish the effects of midlife aging from early postmenopause on vitamin K measures, bone formation biomarkers, and bone density. DESIGN: Cycling older volunteers (CO; 40-52 years, n = 19) were compared to cycling young (CY; 20-30 years, n = 21) and untreated, age-matched women in the early postmenopause years (EPM; 40-52 years, mean years PM = 2.8 +/- 0.5, n = 19). We assessed sex steroids, vitamin status (phylloquinone, 25-hydroxyvitamin D, retinol), osteocalcin (OC), percentage of undercarboxylated osteocalcin (%ucOC), and bone mineral density (BMD) at the spine and hip with dual-energy x-ray absorptiometry. RESULTS: CO women had similar estradiol and vitamin status as CY women, but lower OC (0.64 +/- 0.04 vs 0.97 +/- 0.08 nmol/L, P = 0.01) and BMD at the total hip (1.0038 +/- 0.032 vs 1.1126 +/- 0.030 g/cm2, P = 0.02). In the two older groups, BMD was similar at all sites, but OC was elevated in the EPM women (1.10 +/- 0.10 vs 0.64 +/- 0.04 nmol/L, EPM vs CO, P = 0.001). Although phylloquinone was highest in the EPM women, %ucOC was also higher when compared with all cycling women (21.9 +/- 1.7% vs 17.4 +/- 0.9%, n = 40; P = 0.02). CONCLUSIONS: Premenopausal women show reduced BMD despite normal estrogen profiles. %ucOC may be a specific bone marker of the early postmenopause in healthy women.

Intake of dietary soy isoflavones in relation to perimenstrual symptoms of Korean women living in the USA.

This study was conducted to identify the potential relationship between the dietary intake level of soy isoflavones and perimenstrual symptomatology. The research design was a cross-sectional study. The sample was made up of 84 Korean women living in the USA, aged 28-40 years. The Moos Menstrual Distress Questionnaire (MDQ) and the Food Frequency Questionnaire were used as measurement tools. The soy isoflavone intake was significantly correlated with MDQ scores in the menstrual phase. In conclusion, the beneficial effect of dietary soy isoflavones on certain menstrual symptoms was established, suggesting that soy isoflavones could be one of the dietary factors related to the complexity of premenstrual syndrome (PMS). The positive effect of soy isoflavones on PMS warrants further study.

Health-related quality of life issues in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the influence of obesity, fertility status, and androgenism scores on health-related quality of life in women with polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional, correlational. SETTING: Private reproductive endocrinology practice in two southeast U.S. cities. PARTICIPANTS: Convenience sample of 128 women with PCOS, half of whom were attempting to conceive in addition to being treated for PCOS. Most were White (97%), married (78%), with a mean age of 30.4 years (SD +/- 5.5). MAIN OUTCOME MEASURES: The Health-Related Quality of Life Questionnaire (PCOSQ) for women with polycystic ovary syndrome. A laboratory panel and clinical measures, including body mass index, waist-to-hip ratio, and degree of hirsutism. RESULTS: The most common health-related quality of life concern reported by women with PCOS was weight, followed in descending order by menstrual problems, infertility, emotions, and body hair. CONCLUSIONS: The psychological implications of PCOS are easily underestimated and have been largely ignored. Nursing has a pivotal role in recognizing these concerns and implementing therapy to improve quality of life in women with PCOS.

Midlife women's responses to a hospital sleep challenge: aging and menopause effects on sleep architecture.

OBJECTIVE: To distinguish aging from menopause effects on sleep architecture, we studied an episode of disturbed hospital sleep in asymptomatic midlife women during the follicular phase of an ovulatory cycle and three control groups differing by age or menopause status. METHODS: Fifty-one studies were conducted in four groups of volunteers: young cycling (YC, 20-30 years, n = 14), older cycling (OC, 40-50 years, n = 15), ovariectomized receiving estrogen therapy (OVX, 40-50 years, n = 12), and spontaneously postmenopausal (PM, 40-50 years, n = 10). Subjects were admitted to the University Hospital General Clinical Research Center (GCRC) for a first-night sleep study conducted during a 24-hour, frequent blood sampling protocol. RESULTS: Despite similar estrogen concentrations in the YC (28 +/- 4 pg/ml) and OC (34 +/- 6 pg/ml) groups, OC women had reduced sleep efficiency (79% +/- 2%) vs. YC (87% +/- 3%; p = 0.009). In the OVX and PM groups where estrogen concentrations were markedly different, sleep efficiency was also reduced vs. the YC group (OVX vs. YC, 79% +/- 3% vs. 87% +/- 3%, p = 0.05; PM vs. YC, 75% +/- 3% vs. 87% +/- 3%, p = 0.007). Wake time was longer in the three older groups (103 +/- 10 minutes, 101 +/- 12 minutes, 123 +/- 12 minutes for OC, OVX, PM, respectively) vs. YC (63 +/- 13 minutes, p < 0.05). The number of stage shifts was positively associated with advancing age (rho = 0.3, p < 0.03) but not with estrogen concentration. CONCLUSIONS: Aging-related sleep deficits in response to an experimental stressor occur in midlife women prior to menopause.

Elevated early follicular gonadotropin levels in women with unexplained infertility do not provide evidence for disordered gonadotropin-releasing hormone secretion as assessed by luteinizing hormone pulse characteristics.

OBJECTIVE: To determine whether women with rigorously defined unexplained infertility demonstrated altered GnRH secretion, as reflected by serum LH secretion patterns. DESIGN: Prospective observational study. SETTING: National Center for Infertility Research at Michigan. PATIENT(S): Nine women with rigorously defined unexplained infertility and 11 healthy, parous age-matched control women.Gonadotropin-releasing hormone (25 ng/kg) as a bolus injection. MAIN OUTCOME MEASURE(S): Daytime pulse patterns of LH secretion measured every 10 minutes; mean serum concentrations of LH, FSH, E(2), P, PRL, and cortisol; and response to a physiologic dose of GnRH in the early follicular, late follicular, mid-luteal, and late luteal phases of the same menstrual cycle. RESULT(S): Serum LH pulse frequency and pulse amplitude and LH secretion in response to a physiologic bolus of GnRH were not significantly different in unexplained infertility patients at any phase of the cycle. Luteinizing hormone pulse frequency and amplitude, as well as response to GnRH, varied significantly across the cycle. Mean early follicular serum LH and FSH concentrations were significantly higher in unexplained infertility patients than in fertile control subjects (LH: 5.31 +/-.51 vs. 4.03 +/-.33 [mIU/mL +/- SEM]; FSH: 5.81 +/-.63 vs. 3.80 +/-.45) but were not different at any other phase of the cycle. CONCLUSION(S): These data do not support the hypothesis that unexplained infertility is caused by an abnormality in pulsatile GnRH secretion or abnormal pituitary sensitivity to GnRH. However, the results are consistent with a difference in negative feedback from the ovary to the pituitary in unexplained infertility patients that is suggestive of diminished ovarian reserve.