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Biomedical subjects

Henry G Burger

Publications and source records attributed to Henry G Burger.

At least 19 recordsLinked to original sources
PubMed2006

The association between obesity and the diagnosis of androgen deficiency in symptomatic ageing men.

OBJECTIVE: To determine the influence of obesity on the diagnosis of age-related androgen deficiency (AD) in symptomatic men according to current Australian guidelines. DESIGN, SETTING AND PARTICIPANTS: A community-based cohort of healthy ageing men with symptoms suggestive of AD was studied between May 2001 and February 2003. Men were classified as obese or non-obese according to body mass index (BMI) or waist circumference (WC). MAIN OUTCOME MEASURE: Diagnosis of AD according to Endocrine Society of Australia (ESA) guidelines. RESULTS: 223 men aged 54-86 years with mean BMI 27.3 +/- 0.2 kg/m2 (range 20.5-36.2 kg/m2) were recruited; 99 men were obese (BMI > or = 30.0 kg/m2 or WC > or = 102 cm) and 124 men were non-obese. Obese men had lower total testosterone (TT) (12.7 +/- 0.4 v 15.0 +/- 0.4 nmol/L); P < 0.001) and calculated free testosterone (275.7 +/- 7.8 v 299.3 +/- 7.4 pmol/L); P = 0.03) levels than non-obese men. TT levels < 8 nmol/L were recorded in 12% of obese men and 1% of non-obese men. Applying the ESA guidelines for the diagnosis of age-related AD, 15 obese men (15%) and 4 non-obese men (3%) were classified as being eligible for androgen therapy supported by the Pharmaceutical Benefits Scheme (PBS); the relative risk in obese men was 1.92 (95% CI, 1.44-2.55; P < 0.001). CONCLUSION: Obesity is an important determinant of serum TT levels in ageing men. Almost one in seven obese men but only one in 30 non-obese men in our study were eligible for PBS-supported androgen therapy according to Australian guidelines. Although obese men are more likely to have biochemical hypoandrogenism, the clinical implications of this remain uncertain. Studies of testosterone therapy in this group of ageing men are needed to determine whether androgen replacement is beneficial.

Aged↗
PubMed2006

A clinical update on female androgen insufficiency--testosterone testing and treatment in women presenting with low sexual desire.

The diagnosis of female androgen deficiency syndrome is suggested by complaints of a diminished sense of well being, persistent unexplained fatigue and decreased sexual desire, sexual receptivity and pleasure in a woman who is oestrogen-replete and in whom no other significant contributing factors can be identified. The diagnosis is supported by the finding of low circulating concentrations of free testosterone. Barriers to its recognition include the non-specificity of the symptoms and methodological problems due to insensitive testosterone assays. Barriers to its treatment include the unavailability of satisfactory forms of testosterone for administration to women and lack of data regarding long-term safety. Although several conditions lead to clear-cut androgen deficiency, such as hypopituitarism, adrenal and ovarian insufficiency, glucocorticoid therapy and use of oral contraceptives and oral oestrogens, it is important for clinicians to recognise that in normal women, androgen levels decline by 50% from the early 20s to the mid 40s, and hence age-related androgen insufficiency may occur in women in their late 30s and 40s, as well as postmenopausally. Satisfactory measurements of free testosterone requires a sensitive and reliable assay for total testosterone, and quantitation of sex hormone binding globulin, from which free testosterone is readily calculated. Adverse effects of testosterone treatment are few if replacement is monitored to achieve physiological circulating testosterone concentrations. Currently, available methods include testosterone implants and testosterone creams, and transdermal patches and sprays are in development.

Androgens↗
PubMed2006

Hormone therapy in the WHI era.

The announcement in July 2002 in the media of the results of the combined continuous hormone treatment arm of the Women's Health Initiative (WHI) had a profound effect on perceptions about hormone therapy among the lay public and the medical profession. Careful scrutiny of the announcement and the subsequent publications leads to the conclusion that the widespread fear of hormone therapy that was generated was not supported by the facts. WHI was not designed to be, nor can it be, interpreted as a randomised controlled trial of menopausal hormone therapy--rather, it was a trial of chronic disease prevention, particularly aimed at the possible cardiovascular benefits of a specific combination hormone therapy in postmenopausal women. The results, which were consistent with existing data, did not and do not warrant any major change in the previously established guidelines for the use of hormone therapy. Tibolone has emerged as an alternative treatment for menopausal symptoms, but its long-term benefits and risks have yet to be documented.

Aged↗
PubMed2005

Hot flushes during the menopause transition: a longitudinal study in Australian-born women.

OBJECTIVE: To investigate factors associated with the presence, severity, and frequency of hot flushes. DESIGN: A 9-year prospective study of 438 Australian-born women, aged 45 to 55 years and menstruating at baseline. Annual fasting blood collection, physical measurements, and interviews including questions about bothersome hot flushes in previous 2 weeks were performed. A "hot flush index" score was calculated from the product of the severity and frequency data. Data were analyzed using random-effects time-series regression models. RESULTS: A total of 381 women supplied complete data over the follow-up years. A total of 350 women experienced the menopause transition, of whom 60 (17%) never reported bothersome hot flushes. At baseline, women who reported hot flushes were significantly more likely to have higher negative moods, not be in full- or part-time paid work, smoke, and not report exercising every day. Over the 9-year period of the study, variables significantly associated with reporting bothersome hot flushes were relatively young age (P < 0.001), low exercise levels (P < 0.05), low estradiol levels (P < 0.001), high follicle-stimulating hormone (FSH) levels (P < 0.001), smoking (P < 0.01), being in the late menopause transition (P < 0.001), or being postmenopausal (P < 0.001). In women reporting hot flushes, the hot flush index score increased as their FSH levels increased (P < 0.01), as they entered the late stage of the menopause transition (P < 0.001), and as they became postmenopausal (P < 0.05), and decreased with as their age (P < 0.001) and exercise level (P < 0.05) increased. Between-women analyses found that the hot flush index score was greater in women with higher average FSH levels over time (P < 0.05). CONCLUSION: Menopause status, FSH and estradiol levels, age, exercise level, and smoking status all contributed to the experience of bothersome hot flushes.

Affect↗
PubMed2004

Inhibins and ovarian cancer.

The inhibins are produced and secreted by several ovarian cancers. Monitoring serum levels by immunoassay may be a useful diagnostic aid in the initial assessment of this disease and in monitoring its potential recurrence following surgery. The assays are applicable to women after menopause when the majority of ovarian cancers are detected, and when the normal ovarian production of inhibin is low to negligible. A new inhibin immunoassay (total inhibin ELISA) has been developed with the intention of widespread clinical application. The assay readily detects granulosa cell and mucinous tumours. CA125, a widely used ovarian cancer marker, detects the other main ovarian cancer types (serous, endometrioid, undifferentiated) with high sensitivity. The combination of the two tests detects the majority of ovarian cancers with high specificity (95%) and sensitivity (95%). Studies have been undertaken to assess its application to women in the perimenopausal stage and to younger women during normal reproductive life. These studies are providing a platform for the introduction of the test into clinical practice.

CA-125 Antigen↗
PubMed2004

The relative effect of endogenous estradiol and androgens on menopausal bone loss: a longitudinal study.

OBJECTIVE: The aim of this study was to assess the relative strength of the association of endogenous estradiol and androgens with bone loss at the lumbar spine and femoral neck during the menopausal transition. DESIGN: A longitudinal study of a population-based cohort of 159 Australian-born women who at baseline had a mean age of 50.0 years (SD=2.4) and had menstruated in the prior 3 months. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck on up to three occasions. RESULTS: Of the 159 participants, 50 had two BMD measurements and 109 had a third measure. The mean time between the first and final measures for the whole group was 39 months and at the time of the final measures 49% of the participants had become postmenopausal. The mean percentage change/year in lumbar spine BMD was -0.9% (95% CI, -1.1 to -0.6) and at the femoral neck, -0.5% (95% CI, -0.7 to -0.2). A highly significant association with estradiol at the final time point was found, whereas the contribution of estradiol at baseline was negligible. The variance explained by estradiol levels was 19% and 11% for change in BMD at the LS and FN, respectively. Excluding baseline estradiol values and using the average of change in BMD at the LS and FN, the final regression equation estimated that an estradiol level of 330 pmol/l (95% CI, 274 to 386) and 245 pmol/l (95% CI, 194 to 296) is required for preservation of LS and FN BMD, respectively. A stepwise linear regression model was used to assess the effect of age, BMI, estradiol, testosterone, DHEAS, SHBG, and free testosterone index on changes in BMD and found that only the final estradiol level had a significant association with change in BMD. CONCLUSION: Endogenous estradiol was the only hormone among those investigated to have a significant effect on bone mineral density during the menopausal transition.

Bone Density↗
PubMed2004

Menopause transition: Annual changes in serum hormonal patterns over the menstrual cycle in women during a nine-year period prior to menopause.

To examine the hormonal characteristics of menstrual cycles in healthy women approaching menopause, serum hormone profiles were investigated annually in this longitudinal study of 13 healthy women between 4 and 9 yr before menopause and the year of the menopause. Serum FSH, LH, estradiol, progesterone, total inhibin, inhibins A and B, and prolactin were determined in blood samples collected annually three times weekly for 4 wk beginning with the onset of menses. Menstrual bleeding diaries covering this 4- to 9-yr period were also collected allowing the prospective identification of the final menstrual period. A change in serum hormone patterns was observed in cycles approaching menopause, exemplified by an increasing number of cycles of prolonged length with a prolonged follicular phase resulting in a failure to detect a luteal phase rise in serum progesterone within the 4-wk collection period. These prolonged cycles (designated B cycles based on a previous work) were analyzed separately and compared with the remaining ovulatory (D) cycles. No B cycles were identified in any women earlier than 27 cycles from menopause. The proportion of B cycles increased as menopause approached, reaching 62% in the last 10 cycles. The proportion of D cycles decreased accordingly. The B cycles during the initial 4-wk collection period were characterized by elevated FSH, LH, FSH/inhibin A and FSH/inhibin B ratios, and longer duration, although cycle length/subject was not significantly different presumably due to the small number of B cycles. The D cycles showed no changes in hormonal profiles over the 4- to 9-yr time period. These data indicate that there is a time-related change in the character of menstrual cycles as menopause approaches, with an increasing proportion of cycles observed with prolonged follicular phases that may either be delayed ovulatory cycles or anovulatory cycles. The increase in the proportion of B cycles with elevated early follicular phase FSH levels and low inhibin/FSH ratios toward menopause provides a basis for the apparent early increase in serum FSH and decrease in serum inhibins observed previously in studies of the menopause transition based on sampling confined to the follicular phase only. The data amplify and clarify current concepts of the endocrine basis of the menopause transition.

Estradiol↗
PubMed2003

Central abdominal fat and endogenous hormones during the menopausal transition.

OBJECTIVE: To investigate the effect of endogenous hormone levels on central abdominal fat during the menopausal transition in a population-based cohort of Australian-born women. DESIGN: Prospective observational study. SETTING: Population-based sample. Body composition was assessed in the Royal Melbourne Hospital, and interviews were conducted at the patient's home. SUBJECT(S): One hundred two women from the Melbourne Women's Midlife Health Project. Data, physical measures, and blood were obtained by interview when the longitudinal study commenced (baseline) and at the time of the total body scan approximately 5 years later. Body composition was measured using dual-energy X-ray absorptiometry. INTERVENTION(S): None. MAIN OUTCOME MEASURES: Total body fat and central abdominal fat. RESULT(S): The 102 women were either premenopausal or in the early menopausal transition at baseline. At the time of their dual-energy X-ray absorptiometry scan, 31 were in the early menopausal transition, 22 were in the late menopausal transition, and 49 were postmenopausal. Multiple regression analysis found that total percentage of body fat was associated with weight measures, whereas central abdominal fat was also positively associated with baseline free T index (FTI) and with the increase in FTI since baseline. CONCLUSION(S): The major hormonal change associated with central adiposity during the menopausal transition is the increase in the FTI. This effect is significant even after allowing for baseline and final weight.

Abdomen↗
PubMed2003

The role of androgen therapy.

The concept of a female androgen insufficiency syndrome, although not new, remains somewhat controversial. Androgens are quantitatively the predominant sex steroid in women, circulating in the micromolar and nanomolar concentration range, compared with picomolar levels of oestrogens. The most significant biologically active androgen is testosterone (T), which circulates bound tightly to sex-hormone-binding globulin (SHBG) and loosely to albumin. It is generally held that the non-SHBG-bound fraction is the bioavailable moiety. Hence, clinically useful T measurements require data on total concentrations as well as SHBG level. Testosterone insufficiency occurs in a number of circumstances, including hypopituitarism, premature ovarian failure, adrenal failure, exogenous corticosteroid use and oral oestrogen therapy (causing elevation of SHBG and suppression of gonadotrophins). Clinical symptoms of androgen insufficiency include loss of libido, diminished well-being, fatigue and blunted motivation and have been reported to respond well to T replacement, generally without significant side-effects.

Androgens↗
PubMed2003

Response of serum inhibin B and pro-alphaC levels to gonadotrophic stimulation in normal men before and after steroidal contraceptive treatment.

BACKGROUND: Testicular regulation of inhibin B may be influenced by the germ cell complement. METHODS: We examined the effects of gonadotrophin stimulation on serum inhibin B and pro-alphaC in 25 normal men at (i) control (stimulation test 1), (ii) after spermatogenic suppression induced by testosterone plus progestin treatment (stimulation test 2), and (iii) during spermatogenic recovery induced by FSH and/or hCG treatment (stimulation test 3). For each test, subjects received a single injection of 1200 IU FSH or 5000 IU hCG or both. RESULTS: Inhibin B and pro-alphaC fell with spermatogenic suppression (75 and 51% of pre-treatment baseline respectively, P < 0.05). Inhibin B response to FSH (130-144%) was similar in controls and after germ cell suppression. Pro-alphaC response after germ cell suppression compared with control was significantly increased (P < 0.05) with both FSH (210-229% versus 140-185%) and hCG (254-261% versus 145%). All treatments partially restored spermatogenesis with no clear relationship apparent between inhibin B and sperm count. CONCLUSIONS: We conclude that: (i) serum inhibin B and pro-alphaC are only partially gonadotrophin dependent, (ii) spermatogenic suppression does not modify inhibin B response to FSH but enhances pro-alphaC response to both FSH and hCG, and (iii) inhibin B is a poor marker of spermatogenesis in this model of gonadotrophic manipulation in normal men.

Adult↗
PubMed2002

Molecular pathogenesis of granulosa cell tumours.

Granulosa cell tumours (GCT) of the ovary arise from granulosa cells of the ovary on morphological, biochemical and molecular criteria. In order to understand the molecular pathogenesis of these tumours better we have sought to define their molecular phenotype, to identify activating mutations of the FSH-signalling pathway, to characterise their estrogen receptor expression and to explore the hypothesis that GCT may be resistant to inhibin. The pattern of gene expression observed in GCT suggests a phenotype which is similar to that of late preovulatory granulosa cells which would be consistent with activation of the FSH receptor signalling pathway, however, there is no evidence for activating mutations of either the FSH receptor or the associated trimeric G-proteins. Estrogen receptor beta is abundantly expressed in GCT. The various subunits and isoforms of the activin-inhibin receptor are expressed in GCT. These observations provide a basis for future studies of GCT, including further characterisation of signalling pathways known to be important in the regulation of granulosa cell growth and differentiation.

Activin Receptors↗
PubMed2002

Androgen production in women.

OBJECTIVE: To describe the sources, production rates, circulating concentrations, and regulatory mechanisms of the major androgen precursors and androgens in women. DESIGN: Review of the major published literature. RESULT(S): Quantitatively, women secrete greater amounts of androgen than of estrogen. The major circulating steroids generally classified as androgens include dehydroepiandrosterone sulphate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T), and dihydrotestosterone in descending order of serum concentration, though only the latter two bind the androgen receptor. The other three steroids are better considered as pro-androgens. Dehydroepiandrosterone is primarily an adrenal product, regulated by adrenocorticotropic hormone (ACTH) and acting as a precursor for the peripheral synthesis of more potent androgens. Dehydroepiandrosterone is produced by both the ovary and adrenal, as well as being derived from circulating DHEAS. Androstenedione and testosterone are products of the ovary and the adrenal. Testosterone circulates both in its free form, and bound to protein including albumin and sex steroid hormone-binding globulin (SHBG), the levels of which are an important determinant of free testosterone concentration. CONCLUSION(S): The postmenopausal ovary is an androgen-secreting organ and the levels of testosterone are not directly influenced by the menopausal transition or the occurrence of menopause. Dihydrotestosterone (DHT) is primarily a peripheral product of testosterone metabolism. Severe androgen deficiency occurs in hypopituitarism, but other causes may lead to androgen deficiency, including Addison's disease, corticosteroid therapy, chronic illness, estrogen replacement (leads to elevated SHBG and, therefore, low free testosterone), premenopausal ovarian failure, or oophorectomy.

Androgens↗
PubMed2002

Reproductive hormones: ageing and the perimenopause.

This review explores the pituitary-ovarian hormones involved with ageing and the onset of menopause. The serum patterns of pituitary-ovarian hormones throughout the menstrual cycle alter as menopause approaches. The increase in follicular phase FSH prior to menopause is attributed to an early decline in the ovarian hormone, inhibin B, which negatively regulates follicle-stimulating hormone (FSH) secretion. Serum inhibin B is believed to reflect the age-related decrease in ovarian follicle reserve, which is the primary source of serum inhibin B. The later rise in serum luteinizing hormone (LH) during the menopause transition is due to a cessation of ovarian follicle development. Hormonal patterns during the luteal phase of the menstrual cycle also show changes with age but these changes are poorly understood.

Aging↗
PubMed2002

The role of androgen therapy.

The concept of an androgen deficiency syndrome in women is a relatively old one, although it has gained substantially increased attention in recent years. Androgens are quantitatively the predominant sex steroid in women, circulating in the micro- and nanomolar concentration range, compared with picomolar levels of oestrogen. The most significant biologically active androgen is testosterone, which circulates bound tightly to sex hormone-binding globulin (SHBG) and loosely to albumin. It is generally held that the non-SHBG bound fraction is the bioavailable moiety. Hence interpretable testosterone measurements require data on total concentrations as well as the SHBG level. Testosterone deficiency occurs in a number of situations such as hypopituitarism, primary ovarian and adrenal failure, exogenous corticosteroid use and oral oestrogen therapy (due to the elevation of SHBG and suppression of gonadotrophins). Clinical symptoms of androgen deficiency include lethargy, tiredness and loss of sex drive and interest, and have responded well to androgen replacement, generally without significant side-effects.

Adult↗
PubMed2002

Sertoli-Leydig cell tumor of the ovary, a rare cause of precocious puberty in a 12-month-old infant.

We report a 12-month-old infant who presented with a 4-month history of isosexual precocious puberty secondary to an estrogenizing Sertoli-Leydig cell tumor of the ovary. Total serum immunoreactive inhibin and subunits A and B were markedly elevated before surgical resection and subsequently decreased 7 wk later into the normal prepubertal range. Twenty weeks following surgical removal, the patient presented again with central precocious puberty; inhibin B levels were raised on this occasion, a luteinizing releasing hormone stimulation test confirmed central precocious puberty. This is the youngest reported occurrence of this rare sex cord stromal neoplasm. The prognosis of this extremely rare tumor presenting at this early juvenile stage is uncertain. This report illustrates the usefulness of serum inhibin as a tumor marker during therapeutic suppression with leuprorelin acetate for central precocious puberty. Analysis of genomic and tumor DNA revealed a normal nucleotide sequence for the LH receptor and the Galpha(s) gene. To understand the molecular pathogenesis of this tumor we analyzed mRNA levels for the inhibin A and B subunits, FSH receptor, LH receptor aromatase, steroidogenic factor-1 and the ER beta genes. Molecular characterization reveals the presence of genes specific for granulosa and Leydig cells; the relative expression of these genes, in addition to its histologic characteristics, suggests that this tumor may result from a dysdifferentiation of a primordial follicle.

Androstenedione↗