Postmenopausal hormone therapy and quality of life


Objective: To evaluate whether hormonal therapy (HT) had any significant effect on quality of life (QoL) in a selected group of postmenopausal women. Methods: The study was conducted in a specialist private practice in Tygerberg, Cape Town, South Africa, over an 18-month period ending in July 2003. A questionnaire using the Utian Quality of Life (UQoL) scale was posted to all women with established postmenopausal status, seen over this period. 541 questionnaires were posted, 421 returned and 398 could be used. Women gave written informed consent. Results: The average age of the women was 60 years. 313 women (78.6%) were using hormone therapy (HT) while 275 women (69.1%) reported concomitant medical problems. HTusers had significantly higher scores in three of the four QoL domains, namely, occupational ( p =0.046), emotional ( p =0.03), and sexual ( p =0.009). There was no significant difference in the health domain ( p =0.2). Conclusion: This study found that postmenopausal South African women experienced that HT had a positive effect on global quality of life.


Estrogen receptor a as a target for indole-3-carbinol


A wealth of preclinical evidence supports the antitumorigenic properties of indole-3-carbinol (I3C), which is a major bioactive food component in cruciferous vegetables. However, the underlying molecular mechanism(s) accounting for these effects remain unresolved. In the present study, estrogen receptor alpha (ER-a) was identified as a potential molecular target for I3C. Treating MCF-7 cells with 100 AM I3C reduced ER-a mRNA expression by approximately 60% compared to controls. This reduction in ER-a transcript levels was confirmed using real-time polymerase chain reaction. The I3C dimer, 3,3V-diindolylmethane (DIM), was considerably more effective in depressing ER-a mRNA in MCF-7 cells than the monomeric unit. The suppressive effects of 5 AM DIM on ER-a mRNA was comparable to that caused by 100 AM I3C. DIM is known to accumulate in the nucleus and is a preferred ligand for aryl hydrocarbon receptor (AhR) to I3C. The addition of other AhR ligands, a-naphthoflavone (a-NF, 10 AM) and luteolin (10 AM), to the culture media resulted in a similar suppression in ER-a mRNA levels to that caused by 5 AM DIM. Thus, it is likely that the binding of ligands to AhR inhibits nuclear ER-a transcript. The results from these experiments suggest that the antitumorigenic effects of I3C in MCF-7 human breast cancer cells may arise from its ability to reduce ER-a expression through the binding of its metabolite, DIM, to the nuclear AhR.


Estrogen and exercise may be related to body fat distribution and leptin in young women


Objective: To evaluate the effects of estrogen deficiency and exercise on body composition and leptin in young women.
Design: Cross-sectional clinical study.
Setting: Volunteers in an academic research environment.
Patient(s): Three age- and body mass index–matched groups: normal-weight women with exercise-associated amenorrhea, regularly menstruating exercising control women, and regularly menstruating normally active control women.
Intervention(s): Collection of blood samples and measurement of body fat and regional fat distribution by dual-energy x-ray absorptiometry.
Main Outcome Measure(s): Central fat accumulation (i.e., ratio of trunk to extremity fat) and serum concentrations of E2 and leptin.
Result(s): In both regularly menstruating control groups, but not in the amenorrheic women, there was a negative correlation between the serum E2 concentrations and the trunk-to-extremity fat ratio (r  0.4), independent of age, exercise, body fat, and serum T concentrations. In all women, E2 concentrations were positively and exercise inversely correlated to leptin concentrations, independent of body fat.
Conclusion(s): Estradiol level is inversely associated with central fat accumulation only in women with regular menstrual cycles. In all young premenopausal subjects, estrogen secretion influences leptin concentrations independently of body fat.


Understanding the oestrogen action in experimental and clinical atherosclerosis

Whereas hormone replacement/menopause therapy (HRT) in postmenopausal women increases the coronary artery risk, epidemiological studies (protection in premenopaused women) suggest and experimental studies (prevention of the development of fatty streaks in animals) demonstrate a major atheroprotective action of oestradiol (E2). The understanding of the deleterious and beneficial effects of oestrogens is thus required. The immuno-inflammatory system plays a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas E2 favours an anti-inflammatory effect in vitro (cultured cells), it rather elicits in vivo a proinflammation at the level of several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. Endothelium is another important target for E2, as it potentiates endothelial NO and prostacyclin production, thus promoting the beneficial effects as vasorelaxation and inhibition of platelet aggregation. Prostacyclin, but not NO, appears to be involved in the atheroprotective effect of E2. E2 also accelerates endothelial regrowth, thus favouring vascular healing. Finally, most of these effects of E2 are mediated by oestrogen receptor a, and are independent of oestrogen receptor b. In summary, a better understanding of the mechanisms of oestrogen action not only on the normal and atheromatous arteries, but also on innate and adaptive immune responses is required and should help to optimize the prevention of cardiovascular disease after menopause. These mouse models should help to screen existing and future selective oestrogen receptor modulators.


Gonadal steroid regulation of mood: The lessons of premenstrual syndrome


New models for menstrual cycle-related mood disorders provide unique opportunities to gain insight into the processing of emotional information and the regulation of mood state by reproductive steroids. This paper reviews the role of reproductive steroids in aVect regulation and in premenstrual dysphoric disorder (PMD), parses PMD into component processes that suggest potential mediating neurocircuitry, and highlights the importance of and potential contributors to the diVerential sensitivity that permits reproductive steroids to destabilize mood in some but not all women.


Endogenous androgen levels and well-being: differences between premenopausal and postmenopausal women

Objective: We investigated whether there is a relationship between androgens levels and wellbeing in pre- and postmenopausal women.
Design: We randomly recruited 1423 women aged 18 to 75 years from the community via the electoral roll. Each provided a morning blood sample and completed the Psychological General Well Being Index questionnaire on the same day.Women were excluded if they took medication for any psychiatric illness, had abnormal thyroid function, or had documented polycystic ovarian syndrome. Analysis was by linear regression for well-being, including demographic and lifestyle variables as well as serum levels of androgens.
Results: We included 1224 women in the analysis. Being partnered was positively associated with well-being in premenopausal women. In postmenopausal women, well-being was positively related to age and exercising, whereas smoking, obesity, and postmenopausal hormone therapy use were each negatively associated with well-being. None of the measured androgens (total and free testosterone, dehydroepiandrosterone sulfate, and androstenedione) made an independent contribution to well-being in postmenopausal women (n = 603). However, for premenopausal women (n = 621), levels of dehydroepiandrosterone sulfate were independently and positively associated with the domain score for vitality.
Conclusions: Our findings do not support an important independent role for androgens as determinants of well-being in postmenopausal women. That dehydroepiandrosterone sulfate alone is associated with greater vitality in premenopausal women is of interest but requires further evaluation as an a priori hypothesis in another study.