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Biomedical subjects

H G Burger

Publications and source records attributed to H G Burger.

At least 19 recordsLinked to original sources
PubMed2005

Practical guidelines for postmenopausal hormone therapy.

The fourth Amsterdam Menopause Symposium (2-4 October 2004) was dedicated to practical recommendations to guide clinicians after the confusion, concerns, and controversies generated by study results over the previous several years. Those recommendations are summarized in this deliberately concise and user-friendly document, always recognizing that each clinician must help women with their decision-making according to individual needs, desires, and understanding of benefits and risks.

Alzheimer Disease↗
PubMed2005

Serum C-reactive protein and plasma homocysteine levels are associated with hormone therapy use and other factors: a population-based study of middle-aged Australian-born women.

OBJECTIVE: To investigate the associations between C-reactive protein (CRP), homocysteine levels, use of hormone therapy (HT) and other factors. METHODS: A 12-year prospective study of 438 Australian-born women (Melbourne Women's Midlife Health Project), who at baseline were aged 45-55 years, had menstruated in the previous 3 months and were not taking HT. Fasting blood was collected in the 11th follow-up year for CRP, homocysteine, estradiol and follicle stimulating hormone (FSH) levels. Physical measurements and face-to-face interviews obtained information on health and lifestyle variables. RESULTS: A total of 258 women (mean age 60 years) participated in the 11th follow-up year. Multiple regression analysis found that CRP levels were positively associated with body mass index (p < 0.001), HT use (p < 0.01), and negatively associated with statin use (p < 0.005) and exercising (p < 0.05). In postmenopausal women currently not using HT (n = 173) and after adjusting for body mass index, exercise and smoking, CRP was negatively associated with FSH levels (beta = -0.32, p < 0.05). Homocysteine levels were positively associated with smoking (p < 0.001) and negatively associated with HT use (p < 0.05). CONCLUSION: In middle-aged Australian-born women, HT use was associated with increased CRP and decreased homocysteine levels. High CRP levels were also associated with high relative weight, low exercise levels and no statin medication.

Australia↗
PubMed2004

Androgen insufficiency in women: diagnostic and therapeutic implications.

The proposed key symptoms of the female androgen insufficiency syndrome (FAIS) include reduced libido, diminished well being and lowered mood. The diagnosis of FAIS is made on the basis of these symptoms in the setting of a low serum free testosterone level. However, there is currently no readily available inexpensive assay which reliably measures free testosterone levels in the female range. The diagnosis of FAIS is further complicated by the lack of data demonstrating a minimum serum free testosterone level which, if below this, correlates with the symptoms of FAIS. Despite the complexities involved with defining FAIS, the symptoms have been reported to respond well to testosterone replacement. There is a need for formulations of testosterone therapy specifically designed for use in women, along with clear guidelines regarding optimal therapeutic doses and long-term safety data.

Androgens↗
PubMed2004

The menopausal transition: a 9-year prospective population-based study. The Melbourne Women's Midlife Health Project.

OBJECTIVES: To describe the natural history of the menopause in Australian-born women. To determine the hormonal changes relating to the menopausal transition (MT) and how these affect quality of life, bone mineral density, body composition, cardiovascular disease (CVD) risk and memory. DESIGN: A 9-year prospective, observational study of a population-based sample of 438 Australian-born women aged 45-55 years at baseline. By the 9th year, the retention rate was 88%. Interviews, blood sampling, menstrual calendars, quality of life and physical measures were taken annually, and bone mineral density was measured bi-annually. RESULTS: The late MT coincides with changes in estradiol, follicle stimulating hormone, and free testosterone index, decreases in bone density and mastalgia, and increases in central adiposity, vasomotor symptoms, insomnia and vaginal dryness. Levels of total testosterone and dehydroepiandrosterone sulfate are unchanged by the MT. An increase in CVD risk was associated with increases in weight and free testosterone index and a decrease in estradiol. Depressed mood is increased by symptoms and by stressors occurring in the MT. Sexual functioning significantly deteriorates with the MT and aging, but relational factors have major effects. Menstrual cycles became more variable and longer closer to the final menstrual period. CONCLUSIONS: As hormonal changes during the MT directly or indirectly adversely affect quality of life, body composition and CVD risk, maintenance of health parameters in the premenopausal years is crucial for a healthy postmenopause.

Affect↗
PubMed2004

Inhibin/activin and ovarian cancer.

Inhibin and activin are members of the transforming growth factor beta (TGFbeta) family of cytokines produced by the gonads, with a recognised role in regulating pituitary FSH secretion. Inhibin consists of two homologous subunits, alpha and either betaA or betaB (inhibin A and B). Activins are hetero- or homodimers of the beta-subunits. Inhibin and free alpha subunit are known products of two ovarian tumours (granulosa cell tumours and mucinous carcinomas). This observation has provided the basis for the development of a serum diagnostic test to monitor the occurrence and treatment of these cancers. Transgenic mice with an inhibin alpha subunit gene deletion develop stromal/granulosa cell tumours suggesting that the alpha subunit is a tumour suppressor gene. The role of inhibin and activin is reviewed in ovarian cancer both as a measure of proven clinical utility in diagnosis and management and also as a factor in the pathogenesis of these tumours. In order to place these findings into perspective the biology of inhibin/activin and of other members of the TGFbeta superfamily is also discussed.

Activins↗
PubMed2003

Estrogen exposures and memory at midlife: a population-based study of women.

Estrogen loss after natural menopause is hypothesized to impair episodic memory. A total of 326 women aged 52 to 63 years participating in the Melbourne Women's Midlife Health Project completed a word list memory task. Estrogen exposures were inferred from menopausal status, time from final menstrual period, use of hormone therapy, serum estradiol concentration, and other indices. Memory did not vary significantly with most exposures. The authors conclude that episodic verbal memory assessed by word list learning is not substantially affected during the menopausal transition or in the years immediately after natural menopause.

Body Mass Index↗
PubMed2002

Inhibins/activins as diagnostic markers for ovarian cancer.

It is widely recognised that the early detection and subsequent assessment of recurrence of ovarian cancers are key steps for successful treatment. Available serum markers (e.g. CA125) are sensitive for some epithelial carcinomas (e.g. serous, endometrioid, clear cell), however, these markers are less sensitive for granulosa cell tumours and mucinous carcinomas. Serum inhibin is an ovarian product which decreases to non detectable levels after menopause, however, certain ovarian cancers (mucinous carcinomas and sex cord stromal tumours such as granulosa cell tumours) continue to produce inhibin which provides a basis for a serum diagnostic test. Studies from this and other laboratories have investigated the suitability of inhibin as a diagnostic marker by identifying which inhibin (inhibin A (alphabetaA), inhibin B (alphabetaB), free alpha subunit) or activin (betaAbetaA) form is associated with these cancers. Available data show that inhibin assays which detect all inhibin forms, i.e. assays which detect the alpha subunit both as the free form and as an alphabeta subunit dimer provide the highest sensitivity/specificity characteristics as an ovarian cancer diagnostic test. This review will discuss the data supporting these observations and show recent studies in which a new alpha subunit monoclonal antibody-based ELISA is used as a potential diagnostic test. Furthermore, based on the high sensitivity/specificity characteristics of the respective assays for the various types of ovarian cancer, the combination of the inhibin assay with CA125 detects the majority of all ovarian cancers.

Activins↗
PubMed2002

Surgical or medical treatment of polycystic ovary syndrome: a cost-benefit analysis.

With the availability of laparoscopic ovarian cautery, there has been a resurgence in interest in the surgical treatment of clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Comparison of ovulation and pregnancy rates has found no difference in success rates between ovarian cautery and gonadotropin ovulation induction for such women. We have therefore compared the cost of laparoscopic ovarian cautery with that of a typical cycle of gonadotropin ovulation induction, and also found that there is little difference. Because of the potential advantages of ovarian cautery, we recommend this surgery as the next line of treatment if clomiphene citrate fails to induce ovulation in PCOS patients, before gonadotropins are introduced.

Cautery↗
PubMed2002

FSH-regulated gene expression profiles in ovarian tumours and normal ovaries.

Development, growth and function of the ovary are controlled by endocrine and paracrine signals. These may also influence the development of ovarian cancer. The aim of this study was to identify the key molecular markers of the unregulated growth and hormone synthesis seen in ovarian tumours, particularly in granulosa cell tumours (GCT). Genes used in this study were chosen on the basis of our understanding of growth and differentiation in the normal ovary. We sought to define the patterns of gene expression in a panel of epithelial and stromal ovarian tumours. Expression was determined by RT-PCR using gene-specific primers for the FSH receptor (FSHR); the FSH early response genes: regulatory subunit of protein kinase A (RII-beta), cyclin D2 (cycD2) and sgk; and late response markers: cyclooxygenase-2 (COX-2) and the LH receptor (LHR). The GCT had high expression of FSHR compared with normal ovaries and the other tumours. cycD2 and RII-beta and COX-2 genes were also highly expressed in the GCT. sgk and LHR expression was lower in all of the tumours than in normal ovaries. Serous cystadenocarcinomas also had an unexpectedly high expression of COX-2. Comparison of the gene expression profiles between each tumour group suggests a molecular phenotype for GCT that is similar to that reported for FSH stimulated pre-ovulatory granulosa cells.

Adult↗
PubMed2002

Characterization of inhibin forms and their measurement by an inhibin alpha-subunit ELISA in serum from postmenopausal women with ovarian cancer.

The aim of this study was to characterize the molecular wt forms of inhibins A and B and its free alpha-subunit present in serum from women with ovarian cancer as a basis for developing improved monoclonal antibody-based inhibin assays for monitoring ovarian cancer. Three new inhibin alpha-subunit (alphaC) ELISAs were developed using monoclonal antibodies directed to three nonoverlapping peptide regions of the alphaC region of the inhibin alpha-subunit. To characterize serum inhibin molecular wt forms present in women with ovarian cancer, existing inhibin immunoassays (inhibin A, inhibin B, and pro-alphaC) and the new alphaC ELISAs were applied to sera from women with granulosa cell tumors and mucinous carcinomas previously fractionated using a combined immunoaffinity chromatography, preparative SDS-PAGE, and electroelution procedure. The distribution and molecular size of dimeric inhibins and alpha-subunit detected were consistent with known mol wt forms of inhibins A and B and inhibin alpha-subunit and their precursor forms present in serum and follicular fluid from healthy women. The alphaC ELISAs recognized all known forms of inhibin and the free inhibin alpha-subunit, although differences between alphaC ELISAs were observed in their ability to detect high mol wt forms. To assess which of the alphaC ELISAs was preferred in application to ovarian cancer, the alphaC ELISAs were applied to serum from a range of normal postmenopausal women (n = 61) and postmenopausal women (n = 152) with ovarian (serous, mucinous, endometrioid, clear cell carcinomas, and granulosa cell tumors) and nonovarian (breast and colon) cancers. Despite differences in their ability to detect high mol wt forms of inhibin, the alphaC ELISAs showed similar sensitivity (i.e. proportion of cancer patients correctly detected) and specificity (proportion of controls correctly detected) indexes in the detection of mucinous carcinomas (84% and 95%) and granulosa cell tumors (100% and 95%) compared with earlier inhibin RIA or polyclonal antibody-based immunofluorometric assays. A combination of the alphaC ELISAs with the CA125 assay, an ovarian tumor marker that has a high sensitivity and specificity for other ovarian cancers (serous, clear cell, and endometrioid), resulted in an increase in sensitivity/specificity indexes (95% and 95%) for the all ovarian cancer group. These new monoclonal antibody-based inhibin alphaC ELISAs now provide practical and sensitive assays suitable for evaluation as diagnostic tests for monitoring ovarian cancers.

Adenocarcinoma, Mucinous↗
PubMed2002

Differing effects of low-dose estrogen-progestin therapy and pravastatin in postmenopausal hypercholesterolemic women.

BACKGROUND: Most studies examining the potential cardioprotective effects of postmenopausal estrogen have been undertaken in healthy women, with doses that may not be appropriate for long-term intervention. New low-dose estrogen-progestin regimens alleviate postmenopausal symptoms with a favorable side-effect profile; however, little is known of the impact of such regimens in women at increased risk of cardiovascular disease. Hence, we have evaluated the effects of low-dose oral estrogen-progestin therapy on serum lipoprotein lipids, brachial artery reactivity and fibrinogen in hypercholesterolemic postmenopausal women in direct comparison with the effects of pravastatin, a lipid-lowering agent known to reduce cardiovascular events in women. METHODS: In a randomized, double-blind, double-dummy, parallel trial, we studied the effects of continuous combined estrogen-progestin therapy (1 mg 17beta-estradiol with 500 micro g norethisterone acetate daily) or pravastatin (20 mg daily) in 72 postmenopausal women with fasting serum low-density lipoprotein (LDL) cholesterol levels greater than 124 mg/dl after an 8-week run-in diet, over a 24-week period. The primary end-point was percentage change in LDL cholesterol from baseline. RESULTS: The intention-to-treat population comprised 65 women, mean age 59 +/- 6.3 years, and 29 in each group completed the trial. Diet alone reduced LDL cholesterol significantly in both treatment groups, in association with a reduction in weight during this period. Compared with respective baseline values, pravastatin decreased LDL cholesterol and total cholesterol to a greater extent than hormone therapy (p = 0.0001 and 0.003 for difference between treatments, respectively). High-density lipoprotein (HDL) cholesterol levels decreased with hormone therapy, but did not change with pravastatin (p = 0.01). Lipoprotein(a) decreased significantly with hormone therapy only (-14%, 95% confidence interval (CI) -21 to -6%, p = 0.01 for difference between groups). Brachial artery flow-mediated dilatation (FMD) was impaired at baseline, and this increased with hormone therapy (absolute mean change in artery diameter as percentage units 2.07, 95% CI 0.57-3.57, p = 0.009) versus no change with pravastatin (0.19, 95% CI -1.1 to 1.5, p = 0.78), with a near-significant difference between the two groups (p = 0.058). A significant correlation between improved brachial artery FMD and reduction in LDL cholesterol was not observed. Fibrinogen decreased significantly in both treatment groups with no difference between treatments. CONCLUSIONS: In postmenopausal hypercholesterolemic women, pravastatin and hormone therapy exhibited divergent effects. The former lowered total and LDL cholesterol more effectively, whereas hormone therapy lowered lipoprotein(a) significantly and improved brachial artery endothelium-dependent dilatation, independent of the reduction in LDL cholesterol. The modest increase in brachial artery FMD seen is consistent with hypercholesterolemia compromising endothelial integrity, and suggests that the important effect of estrogen on the endothelial microenvironment may be attenuated in women with endothelial dysfunction.

Aged↗
PubMed2001

The inhibins and ovarian cancer.

Interest in inhibin as a marker of ovarian malignancy was stimulated by the description of elevated immunoreactive inhibin levels in the sera of patients with granulosa cell tumours. Several groups have confirmed the value of serum inhibin in the diagnosis and follow-up of patients with this uncommon malignancy. Immunoreactive inhibin levels are also frequently elevated in patients with mucinous cystadenocarcinoma and less frequently in other forms of ovarian tumour. Assay of sera using the specific dimeric inhibin assays has shown that ovarian tumours are able to secrete dimeric inhibin particularly inhibin B. The less specific alpha-subunit directed assays, however, most frequently show elevated concentrations. Used in combination with CA125 as a dual tumour marker, it appears in principle that inhibin can be a useful diagnostic agent. Immunohistochemistry for the inhibin subunits has been reported with increasing frequency as a helpful method to assess suspected ovarian stromal cell tumours. Its diagnostic accuracy for other types of ovarian adenocarcinoma appears less reliable. Expression of the inhibin subunit mRNAs has been demonstrated in a variety of ovarian malignancies. The observation that inhibin levels are elevated in ovarian cancer has stimulated studies of their relevance to the molecular pathogenesis of these malignancies. Findings to date have been largely negative with no evidence for activating mutations of the FSH receptor or of the post-receptor signalling pathway proteins.

Biomarkers, Tumor↗
PubMed2001

The effects of Chinese medicinal herbs on postmenopausal vasomotor symptoms of Australian women. A randomised controlled trial.

OBJECTIVE: To evaluate the effects of a defined formula of Chinese medicinal herbs (CMH) on menopausal symptoms. DESIGN: A double-blind randomised placebo-controlled trial. METHODS: Between August 1998 and April 1999, 55 postmenopausal Australian women recruited from an urban population completed 12 weeks of intervention with either a defined formula of CMH (n = 28) or placebo (n = 27) taken twice daily as a beverage. MAIN OUTCOME MEASURES: The primary end-point was change in frequency of vasomotor events (hot flushes and night sweats). The secondary end-points were changes in score for the domains measured in the Menopause Specific Quality of Life (MENQOL) Questionnaire. RESULTS: There was a reduction in average weekly frequency of vasomotor events with CMH (-15%; 95% CI, -31% to +1%) and with placebo (-31%; 95% CI, -42% to -21%). The difference between groups favoured the use of placebo; however, this was not significant (P=0.09). Although significant reductions in scores for the various domains of the MENQOL Questionnaire were observed for both CMH and placebo, there were no significant differences between the two treatment groups for any domain. There was evidence for effect modification by previous use of natural therapies for the vasomotor, physical and sexual domains of the MENQOL Questionnaire: women with no prior use of natural therapies for their menopausal symptoms responded to therapy, whereas prior users did not. CONCLUSIONS: The defined formula of CMH was no more effective than placebo in reducing vasomotor episodes in Australian postmenopausal women, or in improving any of the four symptom domains in the MENQOL Questionnaire. Three of the MENQOL Questionnaire domains were modified by prior use of natural therapies. This finding has implications for future studies.

Aged↗
PubMed2001

Impaired fasting glycaemia in middle-aged women: a prospective study.

OBJECTIVES: To investigate: (i) the incidence of impaired fasting glycaemia (IFG) developed over 5 y in a population-based sample of Australian-born women; (ii) prospectively the factors which are associated with the development of IFG; (iii) the association of the menopausal transition with the onset of IFG and an increase in serum insulin concentrations. DESIGN AND METHODS: A total of 265 women (110 pre-, 138 peri-, 17 postmenopausal) participants in the longitudinal phase of the Melbourne Women's Midlife Health Project, aged 46-57 and with normal fasting plasma glucose concentrations at the time of the initial measure, were interviewed, had physical measurements and blood taken annually over a 5 y follow-up period. RESULTS: During the study period 43 women (16%) recorded a fasting glucose concentration of > or =6.1 mmol/l (IFG). Women who recorded IFG prospectively had, at the time of the initial measure when fasting glucose concentrations were normal: higher body mass index (BMI), trunk skinfold thicknesses, waist and hip circumferences (P<0.005), lower SHBG, higher free androgen index and serum insulin concentrations (P<0.05), higher systolic blood pressure, serum triglyceride and lower HDL-cholesterol concentrations (P<0.05) than women whose fasting glucose concentrations remained normal. The onset of IFG was not triggered by the menopausal transition or hormone use. Changes in insulin concentration were associated with changes in BMI (P<0.05). CONCLUSION: Women who developed IFG during the menopausal transition exhibited significantly higher levels of body fatness and dyslipidemia, premenopausally, compared with the women who did not develop IFG. The menopausal transition did not have an effect on the development of IFG, but weight gain during this period was associated with an increase in insulin concentration.

Australia↗
PubMed2001

Physiological principles of endocrine replacement: estrogen.

The major biologically active circulating estrogen in both males and females is estradiol (E(2)). Circulating E(2) is a product of the ovarian granulosa cell and the testicular Leydig cell. Its gonadal formation is dependent on A-ring aromatization of its immediate precursor, testosterone, by a particular isoform of the enzyme aromatase, which also catalyses the conversion of the much weaker androgen, androstenedione, to the weak estrogen, estrone. E(2) is also formed in non-gonadal tissues, such as adipose tissue, liver, muscle and brain. Only adipose tissue makes significant extra-gonadal contributions to circulating estrogen. Loss of ovarian function during reproductive life, as a result of loss of gonadotropin secretion (secondary hypogonadism) or as a result of premature ovarian failure (generally defined as cessation of ovarian function prior to age 40), results in loss of the majority of circulating E(2) and of luteal progesterone. Loss of ovarian function at the menopause likewise results in a 90% loss of circulating E(2). The consequences of loss of ovarian function during reproductive life may be severe. Symptoms include hot flushes, night sweats, vaginal dryness and dyspareunia, loss of libido, loss of bone mass with subsequent osteoporosis and abnormalities of cardiovascular function, including a substantial increase in the risk of ischemic heart disease. Various regimens of estrogen replacement have been employed, aiming to eliminate symptoms, restore well-being and avert the consequences of estrogen depletion. The commonly adopted form of replacement is with the low-dose oral contraceptive pill for reasons of convenience, cost, efficacy, general freedom from side effects and the psychological advantage that many of the patient's peer group are also "taking the pill". An often neglected aspect of hormone therapy in the reproductive age group is the therapeutic use of testosterone. The application of such principles to the postmenopausal period is more problematic, as there is a common perception that the menopause is a normal physiological occurrence and that it is therefore not physiological to offer hormone therapy at that time. The pragmatic approach is to recommend standard therapy with estrogen and progestogen for the management of menopausal symptoms and to recommend longer term hormone replacement in the light of the individual's needs and current data with regard to efficacy for protection from osteoporosis and cardiovascular disease.

Estrogen Replacement Therapy↗
PubMed2000

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

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.

Blood Pressure↗