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Endocrine comparison of obese menstruating and amenorrheic women.

10 examine the relationship between obesity and chronic anovulation, we compared basal serum LH, FSH, and PRL levels, determined at 20-min intervals, and basal C21 [progesterone, 17- hydroxyprogesterone , pregnenolone, 17-hydroxypregnenolone ( 17Pe ), and cortisol], C19 [testosterone (T), delta 4-androstenedione (A), and dehydroepiandrosterone] and C18 (estrone and estradiol) steroid hormone concentrations measured at 1- to 2-h intervals for a 24-h period in five normal weight cycling women (NC) and in two groups of weight-matched obese women. Five of the obese women were regularly cycling (OC), and six were amenorrheic (OA). Sex hormone-binding globulin (SHBG) and non-SHBG-bound T and estradiol concentrations were also measured in each woman. Compared to NC women, OC women had normal basal protein and steroid hormone concentrations, except for reduced 17Pe levels (P less than 0.05). Mean SHBG concentrations were reduced by approximately 30%, and non-SHBG-bound T was increased by 70%, although the differences were not significant. In addition, when six precursors of testosterone (pregnenolone, 17Pe , dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone, and A) were considered together as a group and the data analyzed by the kappa 2 test, a reduction in basal levels of these precursors was found in OC women relative to those in NC women (P less than 0.005). In OA women, mean concentrations of SHBG were markedly reduced and those of total T, A, estrone, and non-SHBG-bound T were significantly increased compared to those in both NC and OC women. Mean 24-h concentrations of LH tended to be greatest and FSH lowest in this group, but were not significantly different from those in the other groups. The mean LH pulse frequency was significantly greater in OA than in OC women (P less than 0.05). Mean 24-h PRL and cortisol levels were also reduced in OA women relative to those in NC women. These data suggest the possibility of a compensatory decline in total T production in OC women in an attempt to maintain normal hormonal homeostasis; as a consequence, ovulation continues in a cyclic fashion. In OA women, such compensatory mechanisms are no longer operative. Instead, a central and/or peripheral defect, resulting in overproduction of androgen, may also exist and lead to anovulation in OA women. In conclusion, our data imply that obesity is not a primary factor causing chronic anovulation. However, obesity may aggravate an already existing subtle defect in some women and result in amenorrhea.

Adult↗

Steroid-modulated stromal cell tissue factor expression: a model for the regulation of endometrial hemostasis and menstruation.

This study examined steroidal regulation of tissue factor expression by cultured endometrial stromal cells. Confluent stromal cell cultures derived from cycling human endometria were exposed to vehicle control, 10(-8) mol/L estradiol (E2), 10(-8)-10(-6) mol/L medroxyprogesterone acetate (MPA), or both E2 and MPA for 2-24 days in serum-containing medium. The progestin enhanced immunoreactive and functionally active stromal cell tissue factor content, achieving peak effects by 8-12 days of culture. Although E2 alone was ineffective, it augmented MPA-enhanced tissue factor content by 8 days of culture, with continued increases beyond 20 days. Dose-dependent effects on tissue factor protein content were observed between 10(-8)-10(-6) mol/L MPA added alone or together with E2. The content of tissue factor mRNA was also increased by MPA and synergistically increased by E2 plus MPA. Similar steroidal effects on stromal cell tissue factor protein and mRNA content were observed using a defined medium. After optimal induction of tissue factor expression by E2 plus MPA, removal of these steroids reduced levels of stromal cell tissue factor mRNA and protein, with virtually complete reversal by day 7 of withdrawal. These time-course and dose-response relationships establish in vitro conditions with which to dissect factors controlling endometrial hemostasis, whereas the observed effects of steroid withdrawal establish a novel model for the study of mechanisms regulating normal and abnormal uterine bleeding.

Cells, Cultured↗

Dietary restriction reduces luteinizing hormone (LH) pulse frequency during waking hours and increases LH pulse amplitude during sleep in young menstruating women.

To determine the effect of dietary energy restriction on gonadotropins, we assayed LH and FSH in samples drawn at 10- and 60-min intervals, respectively, over 24 h from seven young women (mean +/- SE gynecological age, 7.7 +/- 1.2 yr) on day 9, 10, or 11 of two menstrual cycles. Cortisol was measured in samples collected at 30-min intervals. During the 4 previous days and the day of sampling, dietary energy intake was set at either 45 or 10 Cal/kg lean body mass.day in random order. Beginning 2 days before treatment, blood was sampled daily at 0800 h and assayed for T3, insulin-like growth factor-I, and insulin. Estradiol was measured in samples collected daily and at 6-h intervals on the day of frequent sampling. By the day of frequent sampling, dietary restriction had reduced T3 20% (P < 0.01), insulin-like growth factor-I 58% (P < 0.001), and insulin 54% (P < 0.001). Twenty-four-hour transverse means for LH (P = 0.3), FSH (P = 0.2), estradiol (P = 0.3), and cortisol (P = 0.13) were unaffected, but LH pulse frequency was reduced 23% (P < 0.01), especially during waking hours, whereas LH pulse amplitude was increased 40% (P = 0.05), especially during sleep. These results support the hypothesis that LH pulsatility depends upon energy availability in women, as it does in other mammalian species.

Adult↗

Responses of catecholestrogen metabolism to acute graded exercise in normal menstruating women before and after training.

It has been hypothesized that exercise-related hypo-estrogenemia occurs as a consequence of increased competition of catecholestrogens (CE) for catechol-O-methyltransferase (COMT). This may result in higher norepinephrine (NE) concentrations, which could interfere with normal gonadotropin pulsatility. The present study investigates the effects of training on CE responses to acute exercise stress. Nine untrained eumenorrheic women (mean percentage of body fat +/-SD: 24.8 +/- 3.1%) volunteered for an intensive 5-day training program. Resting, submaximal, and maximal (tmax) exercise plasma CE, estrogen, and catecholamine responses were determined pre- and post training in both the follicular (FPh) and luteal phase (LPh). Acute exercise stress increased total primary estrogens (E) but had little effect on total 2-hydroxyestrogens (2-OHE) and 2-hydroxyestrogen-monomethylethers (2-MeOE) (= O-methylated CE after competition for catechol-O-methyltransferase). This pattern was not significantly changed by training. However, posttraining LPh mean (+/-SE) plasma E, 2-OHE, and 2-MeOE concentrations were significantly lower (P < 0.05) at each exercise intensity (for 2-OHE: 332 +/- 47 vs. 422 +/- 57 pg/mL at tmax; for 2-MeOE: 317 +/- 26 vs. 354 +/- 34 pg/mL at tmax). Training produced opposite effects on 2-OHE:E ratios (an estimation of CE formation) during acute exercise in the FPh (reduction) and LPh (increase). The 2-MeOE:2-OHE ratio (an estimation of CE activity) showed significantly higher values at tmax in both menstrual phases after training (FPh: +11%; LPh: +23%; P < 0.05). After training, NE values were significantly higher (P < 0.05). The major findings of this study were that: training lowers absolute concentrations of plasma estrogens and CE; the acute exercise challenge altered plasma estrogens but had little effect on CE; estimation of the formation and activity of CE suggests that formation and O-methylation of CE proportionately increases. These findings may be of importance for NE-mediated effects on gonadotropin release.

Adolescent↗

Daily low-dose mifepristone has contraceptive potential by suppressing ovulation and menstruation: a double-blind randomized control trial of 2 and 5 mg per day for 120 days.

Daily administration of progesterone (P) antagonists to women inhibits ovulation and disrupts endometrial function. In this double-blind randomized trial, we have explored the contraceptive potential of two doses of the P antagonist mifepristone in healthy volunteers in Edinburgh and Shanghai. Ninety-eight women (58 in Edinburgh and 40 in Shanghai) were randomized to receive either 2 or 5 mg mifepristone daily for 120 d. Ovarian activity was monitored by the weekly measurement of steroid metabolites in urine and of E2 and P in plasma every month. Endometrial function was assessed by menstrual records, and ultrasound measurement of endometrial thickness was assessed every month. Endometrial biopsy was collected on d 12 of the control cycle and after 60 and 120 d of treatment. Ninety women (50 in Edinburgh and 40 in Shanghai) completed the study. Follicular activity continued during treatment with both doses in Edinburgh women, although ovulation was suppressed in the majority of cycles (90 and 95% of cycles in 2- and 5-mg groups, respectively). The women in Shanghai showed evidence of ovulation in only 3 of 160 months of treatment (2 in 2-mg group and 1 in 5-mg group). The majority of women in both centers were amenorrheic (65% in 2-mg group and 88% in 5-mg group in Edinburgh, and 90% in both dose groups in Shanghai). The endometrial thickness increased significantly in women in Edinburgh and decreased in Shanghai; histology showed either atrophic or cystic changes without evidence of hyperplasia. There was no pregnancy reported in the 200 months of exposure in 50 sexually active women who had used no other method of contraception during the study. We conclude that mifepristone in low daily doses inhibits ovulation and induces amenorrhea in the majority of women and has the potential to be developed as a novel estrogen- free oral contraceptive pill.

Adult↗

How does menstruation affect cognitive competence and psychophysiological response?

Studies of the effect of the menstrual cycle on standardized cognitive tasks, work and academic performance, perceptual-motor performance, and psychophysiological measures are reviewed. The weight of the evidence argues against a menstrual cycle effect on behavior. Studies of self report and of behaviors reflecting self confidence suggest that beliefs of menstrual debilitation remain in the population. Studies of atypical and deviant groups indicate a possible connection between behavior and the menstrual cycle.

Achievement↗