Micro-RNAs involved in cellular proliferation have altered expression profiles in granulosa of young women with diminished ovarian reserve.

PURPOSE: The study aims to determine differences in micro-RNA (miRNA) expression in granulosa (GC) and cumulus cells (CC) between young women with diminished ovarian reserve (DOR) or normal ovarian reserve (NOR). Secondary objective was to identify downstream signaling pathways that could ultimately indicate causes of lower developmental competence of oocytes from young women with DOR. METHODS: The method of the study is prospective cohort study. RESULTS: Of the miRNA, 125 are differentially expressed in GC between DOR and NOR. Only nine miRNA were different in CC; therefore, we focused analysis on GC. In DOR GC, miR-100-5p, miR-16-5p, miR-30a-3p, and miR-193a-3p were significantly downregulated, while miR-155-5p, miR-192-5p, miR-128-3p, miR-486-5p, miR130a-3p, miR-92a-3p, miR-17-3p, miR-221-3p, and miR-175p were increased. This pattern predicted higher cell proliferation in the DOR GC. The primary pathways include MAPK, Wnt, and TGFbeta. CONCLUSIONS: The miRNA pattern identified critical functions in cell proliferation and survival associated with DOR. GC in women with DOR seems to respond differently to the LH surge.

Dehydroepiandrosterone (DHEA) supplementation results in supraphysiologic DHEA-S serum levels and progesterone assay interference that may impact clinical management in IVF.

PURPOSE: Dehydroepiandrosterone (DHEA) is often prescribed for poor responders in IVF in an effort to improve response to ovarian stimulation. The effect of DHEA supplementation and resultant supraphysiologic DHEA-S serum levels on sex steroid assays has not been evaluated in this population. This study seeks to determine the relationship between DHEA supplementation and progesterone measurements to characterize the degree of interference with particular immunoassays. METHODS: Characterization was accomplished in two phases. First, DHEA-S standard control reagents with no progesterone present were assayed for both DHEA-S and progesterone levels. Second, serum pools from 60 unique IVF patients' serum were used to create six pooled serum samples: three from patients on DHEA supplementation and three from patients not on DHEA supplementation. The three pools were composed of patients whose serum fell into low, medium, and high progesterone ranges. Baseline DHEA-S and progesterone were measured, and the mean level of DHEA-S in the mid-range progesterone pool was used as the mid-point for addition of DHEA-S standard to the serum pools from patients without DHEA supplementation. Progesterone from these pools was then measured on three commercially available immunoassay systems. RESULTS: The first experiment revealed a linear increase in progesterone when analyzing the DHEA-S standard ranging from 0.5 µg/dL [corrected] in the blank control (no DHEA-S) to up to 2.0 µg/dL [corrected] in the high control (DHEA-S >700 µg/dL), [corrected] indicating that the DHEA-S cross-reacts with the progesterone assays. In the second experiment, patients' serum DHEA-S and progesterone were measured from pooled serum samples of those taking DHEA and those not taking DHEA. Adding DHEA-S to the pooled serum of those not taking DHEA resulted in a linear increase in progesterone levels on two of three commercially available immunoassays (p < 0.05). CONCLUSIONS: DHEA-S can interfere with standard progesterone immunoassays used in clinical ART programs, and thus serum progesterone levels in IVF patients on DHEA supplementation may not reflect truly bioactive progesterone.

Attitudes towards potentially carrying the FMR1 premutation: before vs after testing of non-carrier females with diminished ovarian reserve.

Diminished ovarian reserve (DOR) and premature ovarian failure are associated with elevated FMR1 CGG repeat alleles. We assessed pretest attitudes about potentially carrying the FMR1 premutation (FXP) (>55 CGG repeats) among reproductive age women compared with attitudes after learning their non-carrier status. Ninety-two women with DOR, regular menses and no family history of Fragile X Syndrome underwent FMR1 testing and completed attitudinal questionnaires before (T1) and 3 months after learning the test results (T2). The analysis utilized signed rank tests and α = 0.05. Very few women thought they were likely to have a FXP (6.6%). More participants thought FMR1 premutations were "serious" at T2 (62.9%) than at T1 (46.1%, p < 0.0003). When asked at T1 to "describe your feelings when you consider that you are potentially a carrier" of a FXP, 10% had negative feelings, 50% felt ambivalent, and 40% had positive feelings. At T2, feelings about not being a carrier were significantly more favorable (p < 0.0001): negative (0%), ambivalent (6.5%), positive (93%). Corroborating prior reports, few women had a negative view of FXP, perhaps anticipating that carrying the FXP explains their infertility. Perception of the seriousness of FXP increased after learning they did not carry the FXP, which would be predicted by health belief models.

Use of SERMs for treatment in postmenopausal women.

Selective estrogen receptor modulators (SERMs) are synthetic non-steroidal agents which have varying estrogen agonist and antagonist activities in different tissues, most likely due to the receptor conformation changes associated with that SERM's binding and the subsequent effect on transcription. Clinical trials aim to differentiate amongst SERMs on selected target tissues for use in postmenopausal women including effects on breast, bone, cardiovascular venous thrombosis risk, endometrium, vagina, vasomotor symptoms, and brain. This paper describes differences in clinical effects on selected target tissues of SERMs that are approved, discontinued or in development. FDA approved SERMs include tamoxifen and toremifene used for prevention and treatment of breast cancer, raloxifene approved for prevention and treatment of osteoporosis and prevention of invasive breast cancer, and ospemifene approved for treatment of dyspareunia from menopausal vaginal atrophy. The FDA approved first tissue selective estrogen complex (TSEC) a pairing of conjugated equine estrogens with the SERM, bazedoxifene. This pairing reduces the risk of endometrial hyperplasia that can occur with the estrogenic component of the TSEC without the need for a progestogen in women with a uterus. It also allows for the estrogenic benefits on relief of hot flashes and prevention of bone loss without stimulating the breast or the endometrium. In clinical practice, the tissue-selective actions of SERMs, alone or paired with estrogens, allow for individualization in meeting the treatment needs of postmenopausal women by providing targeted tissue effects. This article is part of a Special Issue entitled 'Menopause'.

Osteoporosis treatment and prevention for postmenopausal women: current and future therapeutic options.

Osteoporosis, a "silent disease," is often unrecognized until fracture. Lifestyle modification with nutritional counseling is recommended during menopausal transition. Bone density testing is recommended for women aged 65 years and older, younger postmenopausal women with risk factors, or to follow therapy. Bisphosphonates treat osteoporosis (prevent bone resorption). Raloxifene and hormone therapy prevent bone loss and fracture, with extraskeletal benefits. Denosumab treats osteoporosis, although bone effects reverse rapidly. Teriparatide (anabolic therapy) is considered for women at high risk of fracture. Bazedoxifene with conjugated estrogens, novel delivery of teriparatide, new parathyroid hormone proteins, anti-sclerostin antibodies, cathepsin K inhibitors, and stem cell therapies are in testing.

Racial differences in perception of healthy body weight in midlife women: results from the Do Stage Transitions Result in Detectable Effects study.

OBJECTIVE: Perception of healthy body weight may influence health behaviors, including physical activity level, nutritional habits, and health outcomes, and these perceptions may vary importantly by race. Midlife is a critical period for women that typically includes weight gain. We assessed the associations between perception of healthy body weight and body mass index (BMI) and whether they vary by race. METHODS: In the Do Stage Transitions Result in Detectable Effects study, BMI and perception of body weight (healthy, underweight, or overweight) were measured at baseline examination. Multinomial logistic regression models examined the associations, with race (white vs black) as moderator variable. RESULTS: Of 729 women enrolled, 689 women (95%; black, n = 145; white, n = 544) were included in these analyses. Even though the average BMI was higher for black women than for white women (33.1 vs 29.2 kg/m, respectively; P < 0.0001), black women were less likely to report that they weighed too much (relative risk ratio, 0.4; 95% CI, 0.2-0.9; P = 0.022) and more likely to think that they did not weigh enough (relative risk ratio, 14.2; 95% CI, 1.8-110; P = 0.011). CONCLUSIONS: Although black women, in general, face a greater threat of morbidity from weight-related chronic diseases, they are more likely to be accepting of their weight at higher BMIs relative to whites. Weight loss interventions and counseling about healthy body size may influence healthy behavior and reduce the risk of chronic diseases.