Showing papers by "Henry G. Burger published in 2000"

A Prospective Longitudinal Study of Serum Testosterone, Dehydroepiandrosterone Sulfate, and Sex Hormone-Binding Globulin Levels Through the Menopause Transition

Abstract: The aims of this study were to describe, in relation to date of final menses, the average androgen levels of women in the years before and after this date, and to determine the extent to which these average levels were dependent on age and body mass index (BMI) and the degree of tracking in residual androgen levels, or the extent to which individuals above (below) the mean for their age or time relative to final menstrual period (FMP) and BMI remain above (below) the mean as time progresses. Serial levels of serum sex hormone-binding globulin (SHBG), testosterone (T), and dehydroepiandrosterone sulfate (DHEAS) were measured annually in 172 women from the Melbourne Women's Midlife Health Project who experienced a natural menopause during 7 yr of follow-up. Fasting blood samples were drawn between days 4-8 if women were still menstruating or after 3 months of amenorrhea. The free androgen index (FAI) was calculated as the ratio ofT to SHBG x 100. Means of the log-transformed androgen levels were analyzed as a double logistic function of time relative to FMP as well as age and BMI, and correlations between repeated androgen levels were measured. Mean SHBG levels decreased by 43% from 4 yr before to 2 yr after the FMP. The time of most change was 2 yr before FMP [95% confidence interval (CI), 0.8-3.2]. SHBG levels were, on the average, 5% lower for each halving of estradiol (E2) levels and 4% lower for each kilogram per m2 of BMI (P < 0.0001). About one third of the decline in SHBG was explained by E2 and BMI. After adjusting for all variables, SHBG showed strong tracking. Mean T levels did not vary with time relative to FMP and were independent of age and BMI. Residual values of T showed weak tracking. The FAI increased by 80% from 4 yr before FMP to 2 yr after FMP, and changed maximally 2.2 yr before FMP (95% CI, 1.2-3.2). The FAI was not related to age or E2, but was, on the average, 4% higher for each kilogram per m2 of BMI (P < 0.0001). Residual values of FAI showed moderate tracking. Mean DHEAS levels were not related to the FMP, but were 1.5% lower for each year of age (P < 0.01) and 3.8% lower for each kilogram per m2 of BMI (P < 0.0001). Residual values of DHEAS showed strong tracking. It is concluded that SHBG and FAI levels change at the time of the menopause, at least partially due to the decline in E2. DHEAS decreases as a function of age, not time relative to FMP, and T remains unchanged during the menopausal years. SHBG and DHEAS show a high degree of stability within an individual over time.

Longitudinal study of risk factors for coronary heart disease across the menopausal transition.

Abstract: The patterns of change in blood lipids, diastolic blood pressure, body mass index, smoking and drinking behaviors, and exercise were examined in an ongoing longitudinal study from 1991 to 1995 of 150 middle-aged Melbourne, Australia, women as they passed through menopause. Changes in risk factors over time were examined with reference to time of the final menstrual period (FMP). Random effects models were fitted with adjustments for repeated measures and other covariates, including age. There were overall net increases between 3 years before and the 3 years after menopause of 0.25 mmol/liter for low density lipoprotein cholesterol, 0.05 mmol/liter for high density lipoprotein cholesterol (HDL cholesterol), 0.34 mmol/liter for triglycerides, 0.12 kg/m2 for body mass index, and 0.48 mmHg for diastolic pressure. The proportion of drinkers decreased by 13%, that of smokers increased by 17%, and that of women who exercised at least once a week increased by 6%. The only change dependent on the FMP was a significant decrease in HDL cholesterol (counterbalanced by a similar rise in HDL cholesterol in the year before the FMP), and the rate of decrease was maximal around 9 months after menses ceased, with an instantaneous estimate of slope of 0.55 mmol/liter per year.

Estrogen receptor isoform gene expression in ovarian stromal and epithelial tumors.

Abstract: The factors involved in the pathogenesis of ovarian cancers remain unclear, and the response of these tumors to hormonal therapy is limited. The identification of a second estrogen receptor gene (ERbeta), expressed predominantly in ovarian granulosa cells, led us to explore its possible role in ovarian cancer, particularly in granulosa cell tumors (GCT). Several isoforms of ERbeta have been identified. We sought to define the patterns of both ERalpha and ERbeta gene expression in a panel of ovarian tumors consisting of GCT and serous and mucinous cystadenocarcinomas as well as in normal ovary. Expression was determined by RT-PCR using gene- and isoform-specific primers and probes combined with Southern blot analysis of the PCR products. Widespread expression of ERalpha was observed in all tumor types, but at relatively low levels. ERbeta is expressed predominantly in GCT, with lower levels in mucinous tumors and very low levels in serous tumors. The ERbeta2 splice variant previously reported in rodents was not observed. Only very low levels of the exon 5, exon 6, and exon 5/6 deletion variants were detected. The C-terminal truncation variant ERbeta(cx), however, exhibited widespread expression across all the tumor types. As ERbeta(cx) has been shown to be a ligand-independent antagonist of ERalpha action, the relative ratios of ERbeta(cx), ERalpha, and ERbeta may influence the response of a tumor to antiestrogen therapy.

Phytoestrogens and breast cancer in postmenopausal women: a case control study.

Abstract: Objective To examine the association between isoflavones, androgens, and dietary composition and the risk of breast cancer in Australian postmenopausal women. Design Eighteen women with recently diagnosed breast cancer before surgery and 20 controls were recruited over a 12-month period. Both cases and controls were similarly assessed for urinary isoflavones, serum and urinary sex steroids, and dietary intake. Results Women with breast cancer had lower 24-h urinary daidzein compared with controls (cases: 31 [95% CI: 4, 234] nmol/day; controls: 427 [95% CI: 4, 234] nmol/day; p = 0.03), and there was a trend to lower urinary genistein excretion (cases: 25 [95% CI: 5, 132] nmol/day; controls: 155 [95% CI: 43, 550] nmol/day; p = 0.08). Total testosterone was higher in women with breast cancer compared with controls (cases: 1.3 [95% CI: 1.1, 1.5] nmol/L; controls: 1.0 [95% CI: 0.8, 1.11 nmol/L; p = 0.05). No significant differences were found for serum sex hormone binding globulin, free androgen index, dehydroepiandrosterone sulphate, estradiol and progesterone, or in urinary androgen metabolites, or in dietary intake with regard to fat, carbohydrate, protein, or fiber consumption between cases and controls. Conclusions This preliminary study is the first report of low urinary daidzein and genistein in postmenopausal women with breast cancer. These findings are in keeping with the increasing observational data demonstrating a protective effect from phytoestrogens on breast cancer risk.

Prevalence of gestational diabetes mellitus in polycystic ovarian syndrome (PCOS) patients pregnant after ovulation induction with gonadotrophins.

Abstract: SUMMARY Our aims were: 1 To investigate if women with PCOS who become pregnant using gonadotrophins have a higher incidence of gestational diabetes mellitus (GDM) compared to spontaneously pregnant matched control women, 2 To compare the prevalence of GDM in PCOS women with that in women with hypo/eugonadotrophic hypogonadism and in unexplained infertility and 3 To investigate differences in pregnancy outcomes between the groups. This was a retrospective case-control study. Women with PCOS were matched with a control by age, BMI, and ethnicity. There were 60 women with PCOS, 11 with hypogonadotrophic hypogonadism, 6 with eugonadotrophic hypogonadism, and 12 with unexplained infertility. Control women were those who attended a major public hospital for antenatal care and delivery. We found no difference in the prevalence of GDM between the PCOS (22%) and the controls (17%) or between the PCOS and other groups. Women with GDM (diet or insulin controlled) had a significantly higher BMI than women without GDM (p = 0.019). There was no difference in pregnancy outcomes between the groups. There was a significant dependence of babies' birth weight on mother's BMI (p <0.001).

Early follicular phase serum FSH as a function of age: the roles of inhibin B, inhibin A and estradiol.

Abstract: Objective Reproductive aging in regularly cycling normal women is characterized by a gradual decline in ovarian follicle number and a progressive increase in serum follicle stimulating hormone (FSH), particularly over the age of 40 years. The lack of any consistent decrease in circulating estradiol and progesterone has led to the hypothesis that the FSH increase results from decreasing ovarian inhibin production. The aim of this study was to investigate the relationship between serum inhibins A and B, FSH and estradiol in normal women between the ages of 20 and 50 years.Design and patients Serum from 66 regularly cycling subjects, aged 20–50 years, was collected on days 3–5 of the menstrual cycle for this cross-sectional study.Measurements Serum inhibin A and inhibin B levels were measured by specific enzyme-linked immunosorbent assays (ELISAs). Alpha subunit forms were determined by an immunofluorometric assay which detects all known monomeric and dimeric forms of inhibin A and inhibin B and free α subun...

Biological and Psychosocial Factors Affecting Sexual Functioning During the Menopausal Transition

Abstract: There has been much controversy about whether women experience changes in sexual functioning during the menopausal transition. Studies of women attending menopause clinics report a high prevalence of sexual difficulties and marital problems (1). Clinicians and scientists are therefore concerned about whether aspects of sexual functioning diminish with the menopausal transition. If changes do occur, then does this reflect particular hormonal changes, or concomitant aging?

Inhibins A and B are regulated differentially in the early post-partum period.

Abstract: Background The early postpartum period is characterized endocrinologically by a rapid fall in the levels of oestradiol (E2) and immunoreactive inhibin, and a delayed rise in serum follicle stimulating hormone (FSH). No description is currently available of changes in serum inhibins A and B. Objectives The present study aimed to examine the levels of inhibin A and B during the early weeks of postpartum lactational amenorrhoea, to determine whether there was evidence for differential regulation of the two hormones at a time when no dominant follicle was developing in the ovary. Subjects and methods Serum samples were available from 12 subjects aged 29-38 in whom postpartum levels of FSH, immunoreactive inhibin, E2 and prolactin had been examined previously. Samples for hormone assays had been obtained prior to delivery, daily for the 3-5 days postpartum, and weekly thereafter. Inhibins A and B were measured by specific ELISA assays, and results were calculated as 10 day averages for samples obtained on days 1-10, 11-20, 21-30, etc. postpartum. Normal hormone concentrations for reference were obtained from volunteers, also aged 29-38, sampled on days 3-5 of a normal menstrual cycle. Results Inhibin A in the predelivery sample ranged from 62 to 1243 ng/l, geometric mean 592. Concentrations fell rapidly postpartum and reached a nadir in the low follicular phase range between days 5 and 37 postdelivery, mean 13.6 days. The concentrations of both inhibin B and FSH rose 14-27 days postpartum from their initially low postdelivery levels, to reach the normal follicular phase range. These increases in concentration were significantly correlated in all individual subjects. Conclusions The secretion of inhibin A and B is regulated differentially during the early stages of lactational amenorrhoea, just as it is in the late luteal phase of the normal menstrual cycle. Whilst inhibin A falls postpartum, reflecting cessation of placental function, and remains low until ovulatory cycles are resumed, FSH and inhibin B rise after a delay of two weeks or more. It is postulated that the rise of inhibin B is the result of secretion from a cohort of small follicles stimulated by rising FSH levels.

CHAPTER 9 – Perimenopausal Changes in FSH, the Inhibins, and the Circulating Steroid Hormone Milieu

Abstract: The perimenopause is a time of markedly fluctuating hormone levels. Attempts to define menopausal status purely on the basis of single measurements of FSH or E 2 are unlikely to yield useful information. Though E 2 concentrations appear to be preserved in regularly cycling women at least until the age of 50, INH-B declines and FSH rises. The establishment of menstrual irregularity is marked by a decrease in the follicular-phase concentrations of INH-B, an increase in FSH, but relative preservation of E 2 and INH-A until the time of the FMP. The frequency of anovulatory cycles increases markedly as the FMP approaches. It is difficult to demonstrate substantial changes in androgen concentrations in the immediate perimenopausal period, though levels postmenopausally appear to be lower than those of young regularly cycling women, perhaps as a function of increasing age rather than menopausal status. Hormonal measurements are of little diagnostic value during the perimenopause other than for the purposes of physiological study.