Henry G. Burger

A prospective population-based study of menopausal symptoms☆

Objective To identify symptoms that change in prevalence and severity during midlife and evaluate their relationships to menopausal status, hormonal levels, and other factors. Methods In a longitudinal, population-based study of 438 Australian-born women observed for 7 years with an 89% retention rate, 172 advanced from premenopause to perimenopause or postmenopause. Annual measures included a 33-item symptom check list; psychosocial, lifestyle, and health-related factors; menstrual status; hormone usage; and blood levels of follicle-stimulating hormone and estradiol (E2). Results Increasing from early to late perimenopause were the number of women who reported five or more symptoms (+14%), hot flushes (+27%), night sweats (+17%) and vaginal dryness (+17%) (all P < .05). Breast soreness-tenderness decreased with the menopausal transition (−21%). Trouble sleeping increased by +6%. The major change in prevalence was from early to late perimenopause, except for insomnia, which showed a gradual increase. Those variables most related to onset of hot flushes were number of symptoms at early perimenopause (P < .05), having an unskilled or no occupation (P < .05), more than 10 pack-years of smoking (P < .01), and decreased E2 (P < .01). The onset of night sweats increased with the change in E2 (P < .05). The onset of vaginal dryness decreased with more years of education (P < .05). Trouble sleeping was predicted by prior lower well-being (P < .01), belief at baseline that women with many interests hardly notice menopause (P < .01), and hot flushes (P < .01). Conclusion Although middle-aged women are highly symptomatic, the symptoms that appear to be specifically related to hormonal changes of menopausal transition are vasomotor symptoms, vaginal dryness, and breast tenderness. Insomnia reflected bothersome hot flushes and psychosocial factors.

Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality.

To investigate the role of androgens in increasing bone density and improving low libido in postmenopausal women, we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospective, 2 year, single-blind randomised trial. Thirty-four postmenopausal volunteers were randomised to treatment with either estradiol implants 50 mg alone (E) or estradiol 50 mg plus testosterone 50 mg (E&T), administered 3-monthly for 2 years. Cyclical oral progestins were taken by those women with an intact uterus. Thirty-two women completed the study. BMD (DEXA) of total body, lumbar vertebrae (L1-L4) and hip area increased significantly in both treatment groups. BMD increased more rapidly in the testosterone treated group at all sites. A substantially greater increase in BMD occurred in the E&T group for total body (P < 0.008), vertebral L1-L4 (P < 0.001) and trochanteric (P < 0.005) measurements. All sexual parameters (Sabbatsberg sexual self-rating scale) improved significantly in both groups. Addition of testosterone resulted in a significantly greater improvement compared to E for sexual activity (P < 0.03), satisfaction (P < 0.03), pleasure (P < 0.01), orgasm (P < 0.035) and relevancy (P < 0.05). Total cholesterol and LDL-cholesterol fell in both groups as did total body fat. Total body fat-free mass (DEXA, anthropometry, impedance) increased in the E&T group only. We concluded that in postmenopausal women, treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone. Significantly greater improvement in sexuality was observed with combined therapy, verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women. The favourable estrogenic effects on lipids were preserved in women treated with T, in association with beneficial changes in body composition.

Postmenopausal hormone therapy: An endocrine society scientific statement

OBJECTIVE Our objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint. PARTICIPANTS IN DEVELOPMENT OF SCIENTIFIC STATEMENT: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.S.) and suggested experts with expertise in specific areas. In conjunction with the Task Force, lead authors (n = 25) and peer reviewers (n = 14) for each specific topic were selected. All discussions regarding content and grading of evidence occurred via teleconference or electronic and written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement. EVIDENCE Each expert conducted extensive literature searches of case control, cohort, and randomized controlled trials as well as meta-analyses, Cochrane reviews, and Position Statements from other professional societies in order to compile and evaluate available evidence. No unpublished data were used to draw conclusions from the evidence. CONSENSUS PROCESS A consensus was reached after several iterations. Each topic was considered separately, and a consensus was achieved as to content to be included and conclusions reached between the primary author and the peer reviewer specific to that topic. In a separate iteration, the quality of evidence was judged using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system in common use by The Endocrine Society for preparing clinical guidelines. The final iteration involved responses to four levels of additional review: 1) general comments offered by each of the 25 authors; 2) comments of the individual Task Force members; 3) critiques by the reviewers of the Journal of Clinical Endocrinology & Metabolism; and 4) suggestions offered by the Council and members of The Endocrine Society. The lead author compiled each individual topic into a coherent document and finalized the content for the final Statement. The writing process was analogous to preparation of a multiauthored textbook with input from individual authors and the textbook editors. CONCLUSIONS The major conclusions related to the overall benefits and risks of MHT expressed as the number of women per 1000 taking MHT for 5 yr who would experience benefit or harm. Primary areas of benefit included relief of hot flashes and symptoms of urogenital atrophy and prevention of fractures and diabetes. Risks included venothrombotic episodes, stroke, and cholecystitis. In the subgroup of women starting MHT between ages 50 and 59 or less than 10 yr after onset of menopause, congruent trends suggested additional benefit including reduction of overall mortality and coronary artery disease. In this subgroup, estrogen plus some progestogens increased the risk of breast cancer, whereas estrogen alone did not. Beneficial effects on colorectal and endometrial cancer and harmful effects on ovarian cancer occurred but affected only a small number of women. Data from the various Womens Health Initiative studies, which involved women of average age 63, cannot be appropriately applied to calculate risks and benefits of MHT in women starting shortly after menopause. At the present time, assessments of benefit and risk in these younger women are based on lower levels of evidence.

Dietary flour supplementation decreases post-menopausal hot flushes: Effect of soy and wheat

Plants contain compounds with oestrogen--like action called phytoestrogens. Soy contains daidzin, a potent phytoestrogen, and wheat flour contains less potent enterolactones. We aimed to show in 58 postmenopausal women (age 54, range 30-70 years) with at least 14 hot flushes per week, that their daily diet supplemented with soy flour (n = 28) could reduce flushes compared with wheat flour (n = 30) over 12 weeks when randomised and double blind. Hot flushes significantly decreased in the soy and wheat flour groups (40% and 25% reduction, respectively < 0.001 for both) with a significant rapid response in the soy flour group in 6 weeks (P < 0.001) that continued. Menopausal symptom score decreased significantly in both groups (P < 0.05). Urinary daidzein excretion confirmed compliance. Vaginal cell maturation, plasma lipids and urinary calcium remained unchanged. Serum FSH decreased and urinary hydroxyproline increased in the wheat flour group.

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 Addisons disease, corticosteroid therapy, chronic illness, estrogen replacement (leads to elevated SHBG and, therefore, low free testosterone), premenopausal ovarian failure, or oophorectomy.

Hormones, mood, sexuality, and the menopausal transition

OBJECTIVE To determine the extent of changes in womens sexual functioning and well-being during the menopausal transition and the relationship to hormonal changes. DESIGN Prospective observational study. SETTING Population-based sample assessed at home. PATIENT(S) 438 Australian-born women 45-55 of years who were still menstruating at baseline. Of these, 226 were studied for effects of hormones on sexual functioning. MAIN OUTCOME MEASURE(S) Short Personal Experiences Questionnaire (SPEQ) and Affectometer 2 scores and annual blood sampling. RESULT(S) From the early to late menopausal transition, the percentage of women with SPEQ scores indicating sexual dysfunction increased from 42% to 88%. Mood scores did not change significantly. In the early menopausal transition, women with low total SPEQ scores had lower estradiol level but similar androgen levels to those with higher scores. Decreasing SPEQ scores correlated with decreasing estradiol level but not with androgen levels. Hormone levels were not related to mood scores. CONCLUSION(S) Female sexual functioning declines with the natural menopausal transition. This decline relates more to decreasing estradiol levels than to androgen levels.

Are changes in sexual functioning during midlife due to aging or menopause

OBJECTIVE To determine whether changes in womens sexual functioning during midlife are due to aging or menopause. DESIGN Prospective, observational study. SETTING Population-based sample assessed in own homes. PATIENT(S) Four hundred thirty-eight Australian-born women aged 45-55 years and still menstruating at baseline. One hundred ninety-seven were studied for effects of the natural menopausal transition. Control group A (n = 44) remained premenopausal or early perimenopausal for 7 years. Control group B (n = 42) remained postmenopausal over 5 years. INTERVENTION(S) Nil; questionnaires and blood sampling annually. MAIN OUTCOME MEASURE(S) Shortened version of the Personal Experiences Questionnaire. RESULT(S) By the late perimenopause, there was a significant decline in the factors we had derived of sexual responsivity and total score, and there was an increase in the partners problems factor. By the postmenopausal phase, there was a further decline in the factors sexual responsivity, frequency of sexual activities, libido, and in the total score, and a significant increase in vaginal dyspareunia and partners problems. Sexual responsivity significantly declined in both control groups. CONCLUSION(S) Sexual responsivity is adversely affected by both aging and the menopausal transition. Other domains of female sexual functioning were significantly adversely affected when the women became postmenopausal. The relationship with the partner and his ability to perform sexually is adversely affected by the menopausal transition.

The endocrinology of the menopause

Changes in the endocrinology of the pituitary-ovarian axis first become manifest at about the age of 40, a selective rise in serum follicle stimulating hormone (FSH) levels occurring at about the same time as a marked acceleration in the loss of primordial follicles from the ovary. FSH levels gradually increase with increasing age in women who continue to cycle regularly. During the menopausal transition, initiated when changes in cycle frequency or in menstrual flow are first observed, both gonadotrophins, oestradiol and inhibin show a marked degree of variability with abrupt changes from typical post-menopausal patterns to those characteristic of the reproductive age group. Within 1-2 years after the final menstrual period or menopause, FSH levels are markedly elevated, luteinizing hormone (LH) levels moderately so, while oestradiol and inhibin levels are low or undetectable. Post-menopausally, adrenal androstenedione is the major source of oestrogen and serum testosterone levels fall moderately, with oophorectomy leading to a further significant fall. Serum sex hormone binding globulin levels fall to a small degree post-menopausally. Areas of persisting controversy include the question of whether oestradiol levels fall with increasing age prior to the onset of the menopausal transition, the relative roles of oestradiol and inhibin in the selective rise of serum FSH and the role of serum androgens post-menopausally.

Elevated Serum Inhibin Concentrations in Postmenopausal Women with Ovarian Tumors

Background Inhibin is an ovarian hormone that inhibits the secretion of follicle-stimulating hormone (FSH) by the anterior pituitary gland. Women with granulosa-cell tumors of the ovary have elevated serum inhibin concentrations, but whether the concentrations are increased in women with other ovarian tumors is unknown. Methods We measured serum inhibin and FSH concentrations before surgery in 212 postmenopausal women with suspected ovarian cancer and after surgery in 210 of them. Results Eighteen of the 22 women (82 percent) with mucinous carcinomas (mucinous cystadenocarcinomas and mucinous borderline cystic tumors) of the ovary had elevated serum inhibin concentrations, whereas only 9 of the 53 women (17 percent) with serous carcinomas (serous cystadenocarcinomas and serous borderline cystic tumors) had elevated levels. Serum inhibin concentrations were also elevated in 2 of 12 women (17 percent) with clear-cell carcinomas, 4 of 26 women (15 percent) with undifferentiated carcinomas, 3 of 3 women (100 ...

Age related changes in follicle stimulating hormone, luteinizing hormone, oestradiol and immunoreactive inhibin in women of reproductive age

objective In women over the age of 45 years with continuing regular menstrual cycles, follicular phase FSH levels rise without an accompanying change in LH. We determined the effect of increasing age in women with regular cycles on the serum levels of FSH, LH, Immunoreactive Inhibin, progesterone and oestradiol