Premenopausal women show reduced BMD despite normal estrogen profiles. %ucOC may be a specific bone marker of the early postmenopause in healthy women.

Objective-To test whether black cohosh (BC) exhibits an action on the central endogenous opioid system in postmenopausal women.Design-A mechanistic study conducted in the same individuals of LH pulsatility with a saline/ naloxone (NAL) challenge (n=6) and PET imaging with [ 11 C]carfentanil, a selective μ-opioid receptor radioligand (n= 5), before and after 12 weeks of unblinded treatment with a popular black cohosh daily supplement.Results-Black cohosh treatment for 12 weeks at a standard dose (Remifemin, 40 mg/day) had no effect on spontaneous LH pulsatility or estrogen concentrations. With NAL blockade, there was an unexpected suppression of mean LH pulse frequency (saline vs NAL = 9.0+.6 vs 6.0+.7 pulses/ 16 hrs; p= 0.056), especially during sleep when the mean interpulse interval (IPI) was prolonged by approximately 90 minutes (SAL night IPI = 103± 9 mins vs NAL night IPI = 191± 31min, p = 0.03). There were significant increases in μ-opioid receptor binding potential (BP) in the posterior and subgenual cingulate, temporal and orbitofrontal cortex, thalamus and nucleus accumbens ranging from 10% to 61 % across regions -brain regions involved in emotional and cognitive function. In contrast, BP reductions of lesser magnitude were observed in regions known to be involved in the placebo response (anterior cingulate and anterior insular cortex).Conclusion-Using two different challenge paradigms for the examination of central opioid function, a neuropharmacologic action of black cohosh treatment was demonstrated in postmenopausal women.

NARRATIVE ABSTRACTTo assess the involvement of ovarian-derived regulatory proteins in FSH modulation, we compared FSH, inhibin A, inhibin B, activin A and follistatin in 79 women from the following five groups: young cycling (YC), older cycling (OC), 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 group and negatively correlated with advancing age.The monotropic rise in FSH in the late reproductive years prior to menopause is accompanied by declining inhibin B (1-3) and increasing activin A (2,3) in the presence of unchanged follistatin (FS) (2), suggesting the potential for a net stimulatory effect on FSH regulation. To what extent such changes reflect ovarian aging is unknown, because these peptides are also produced in multiple sites including the pituitary (4-7). To better assess the importance of ovarian aging in FSH modulation by these regulators, we compared circulating levels of inhibin A, inhibin B, activin A, and the neutralizing activin-binding protein, follistatin (FS), in women with functioning ovaries in varying pre and perimenopausal states to those in women of similar age after spontaneous menopause or ovariectomy while receiving estrogen replacement therapy.Prior to initiation of the study, approval of the protocol was obtained from the University of Michigan Hospital's institutional review board for use of human subjects. All participants (n = 79) provided written consent. Sixty-three healthy volunteers ages 40−50 yrs were recruited into the following four study groups: older cycling (OC mean age = 45.9 ± 0.8 yrs, n=17), perimenopause (PERI mean age = 49.0 ± 0.6 yrs, n=21), spontaneous menopause (PM mean age = 49.4 ± 0.6 yrs, n = 10), and surgical menopause receiving estrogen (OVX+ET mean age = 49.0±1.6 yrs, n=15). A fifth group of 16 young cycling women (YC mean age = 23.0±.9 yrs) served as controls. All participants had a body mass index of 20−25, and reported no current medical or psychiatric illness, no current use of sex steroid therapy, no pregnancy or breastfeeding in the past 6 months, no current history of dieting, excessive exercise or smoking. Plasma values for prolactin, testosterone and DHEAS, obtained during the screening visit, were Corresponding author: Nancy King Reame, MSN, PhD 630 168 th Street Columbia University New York, NY 10032 212−305−6761 (phone) 212−305−2139 (FAX) nr2188@columbia.eduAddress reprint requests to: Nancy Reame, MSN, PhD 630 168 th Street Columbia University New York, NY 10032 nr2188@columbia.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its fi...

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 non-obese volunteers with regular cycles (CO, n = 19) or in early menopause (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, adiponectin/leptin (A/L) ratio and HOMA-IR. In ovulatory women, AD, estradiol 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 µg/ml vs. CO: 14.0 ± 1.1 µg/ml vs. EPM: 17.7 ± 1.5 µg/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 ≤ 25 kg/m2), leptin concentrations were higher and A/L ratios lower in PRE and EPM overweight subgroups vs. normal-weight subgroups. AD was lower in overweight, cycling women and higher in the normal-weight EPM subgroup compared to normal-weight PRE women. In cycling women, AD did not vary across the menstrual cycle. Conclusion Non-obese, midlife women experience minimal adverse effects from reproductive aging on insulin sensitivity and adipokine secretion. The menstrual cycle is not a key mediator of AD. Early menopause has differential, BMI-dependent effects on adipokine secretion.

Aging-related sleep deficits in response to an experimental stressor occur in midlife women prior to menopause.