DHEA replacement for postmenopausal women: placebo or panacea?

In adults, dehydroepiandrosterone (DHEA) is the most abundant steroid found in serum and its levels fall with age. It can be converted into androgens and estrogens by peripheral tissues. Thus it may be considered to be a pro-hormone. Many websites are promoting oral DHEA as an anti-aging tonic and in some countries it is sold as a supplement. Recent clinical trials of oral DHEA and reviews of those trials have failed to show any health benefits for postmenopausal women. However, there may be a role for vaginal DHEA.

The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolaemia.

The effects of dietary isoflavone supplementation using a purified extract of red clover containing approximately biochanin A 26 mg, formononetin 16 mg, daidzein 0.5 mg and genistein 1 mg per tablet at doses of one or two tablets per day were compared to placebo in a three-period, randomised, double blind, ascending dose study in 66 post menopausal women with plasma cholesterol levels between 5.0 and 9.0 mmol/l. Each treatment period lasted 4 weeks and a further nine women received placebo for the full 12-week period. All women consumed a low isoflavone diet for 2 weeks preceding the commencement of the study and for the 12-week study period. Urinary isoflavone excretion was very low in subjects receiving placebo but increased in a dose-dependent manner during therapy with one and two of isoflavone tablets. Dietary supplementation with isoflavones did not significantly alter total plasma cholesterol, LDL cholesterol, HDL cholesterol or plasma triglyceride levels. However, inverse correlations were found between urinary genistein excretion and plasma triglyceride levels and between urinary O-DMA excretion (an isoflavone metabolite) and plasma triglyceride levels in subjects receiving one isoflavone tablet, suggesting a weak relationship between isoflavone intake and plasma triglycerides which may be influenced by individual differences in isoflavone absorption or metabolism. The results suggest that isoflavone phytoestrogens from red clover in the proportions and quantities studied do not significantly alter plasma lipids in post menopausal women with moderately elevated plasma cholesterol levels.

A review of the clinical effects of phytoestrogens.

OBJECTIVE: To review the sources, metabolism, potencies, and clinical effects of phytoestrogens on humans. DATA SOURCES: The MEDLINE data base for the years 1980-1995 and reference lists of published articles were searched for relevant English-language articles concerning phytoestrogens, soy products, and diets with high-phytoestrogen content. METHODS OF STUDY SELECTION: We identified 861 articles as being relevant. Human cell line studies, human epidemiologic studies (case-control or cohort), randomized trials, and review articles were included. Animal studies regarding phytoestrogens were included when no human data were available concerning an important clinical area. TABULATION, INTEGRATION, AND RESULTS: Included were studies containing information considered pertinent to clinical practice in the areas of growth and development, menopause, cancer, and cardiovascular disease. When findings varied, those presented in this study reflect consensus. All studies concurred that phytoestrogens are biologically active in humans or animals. These compounds inhibit the growth of different cancer cell lines in cell culture and animal models. Human epidemiologic evidence supports the hypothesis that phytoestrogens inhibit cancer formation and growth in humans. Foods containing phytoestrogens reduce cholesterol levels in humans, and cell line, animal, and human data show benefit in treating osteoporosis. CONCLUSION: This review suggests that phytoestrogens are among the dietary factors affording protection against cancer and heart disease in vegetarians. With this epidemiologic and cell line evidence, intervention studies are now an appropriate consideration to assess the clinical effects of phytoestrogens because of the potentially important health benefits associated with the consumption of foods containing these compounds.

The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume.

Fifteen ovulating women had serial ultrasound scans to measure follicular, endometrial, and uterine growth, as well as biochemical indices including estradiol (E2) and the free androgen index, throughout a natural and a clomiphene-citrate-induced cycle. Despite higher E2 levels in the 5 days preceding ovulation, the clomiphene cycles were characterized by absence of the normal increase in uterine volume and an inhibition of endometrial thickening. It is proposed that the anti-estrogen effect of clomiphene inhibits the normal cyclical growth of the uterus and endometrium.

A twin study of polycystic ovary syndrome.

OBJECTIVE: To examine the role of genetic and environmental factors in polycystic ovary syndrome (PCOS) by using the classic twin model. SETTING: Outpatient clinic of the Royal Hospital for Women, Paddington, Sydney, New South Wales, Australia. PATIENTS: A group of 19 monozygotic (MZ) and 15 dizygotic (DZ) twin pairs identified from the national twin register. INTERVENTIONS: Ultrasound, clinical, and biochemical parameters were used to define PCOS. RESULTS: Eleven pairs of twins (5 MZ, 6 DZ pairs) were scan-discordant (i.e., one twin had scan-PCOS and the co-twin did not). Model-fitting analysis suggested that fasting insulin level, androstanediol glucuronide, and body mass index (BMI) were significantly influenced by genetic factors. CONCLUSION: This study suggests that PCOS is not the result of a single autosomal genetic defect, but rather environmental factors, perhaps both intrauterine and extrauterine, are involved in the pathogenesis of this disorder or that PCOS may be an X-linked disorder or the result of polygenic factors. However, fasting insulin level, androstanediol glucuronide, and BMI did appear to be under significant genetic influence.

Estrogen replacement therapy in survivors of breast cancer: a risk-benefit assessment.

The use of hormone replacement therapy (HRT) after breast cancer is controversial. For a minority of such women, menopausal symptoms such as hot flushes can be so severe as to compromise quality of life. Moderate doses of progestogens alone are an effective therapy for hot flushes in around two-thirds of patients and poorly absorbed topical estrogens are well tolerated and effective for vaginal dryness. However, for a small number of women, the only effective therapy for hot flushes is estrogen replacement. Women with early stage breast cancer are unlikely to die from this disease and will be more likely to be affected by age-related diseases such as heart disease, strokes and osteoporotic fractures. These women may also benefit from estrogen replacement. Prospective trials are currently under way to determine the safety of HRT after breast cancer.

Phytoestrogens--a short review.

The wide distribution of plant estrogens or 'phytoestrogens' in cereals, vegetables and medicinal plants raises questions concerning the possible health risks and benefits associated with their consumption. In this article, we provide a synopsis of the literature relating principally to the clinical effects of phytoestrogens on the diseases associated with ageing. The sources, metabolism and properties of the different phytoestrogens are also discussed. The studies included were primarily restricted to those with data pertinent to clinical practice. Our contention is that phytoestrogens are at least part of the reason why vegetarians and Asian populations have a low rate of cancer and heart disease.

Effects of estrogens and hormone replacement therapy on breast cancer risk and on efficacy of breast cancer therapies.

This review summarises preclinical and clinical data on effects of endogenous and exogenous estrogens on probability of breast cancer diagnosis, and on the course and efficacy of breast cancer therapies. The data indicate that higher endogenous estrogen exposure (e.g. pregnancy, early menarche and late menopause, estrogen levels in future breast cancer patients, obesity) or exogenous estrogens (oral contraceptives; hormone replacement therapies) may be associated with an increased probability of breast cancer diagnosis. However, there is little evidence that estrogens have deleterious effects on the course of breast cancer. Moreover, increased incidence of breast cancer diagnosis after prolonged hormone replacement therapy (HRT) use seems to be associated with clinically less advanced disease. In studies assessing both diagnosis and mortality, HRT is frequently associated with reduced mortality compared to never users. The interaction of progestagens and estrogens on the probability of breast cancer diagnosis is complex and dependent on type of progestagens and regimens employed. Efficacy of current treatment modalities for breast cancer (surgery, irradiation, adjuvant therapy or chemotherapy) is not negatively influenced by estrogens at concentrations considerably higher than those attained with current HRT preparations. Although it cannot be excluded that estrogens increase the probability of breast cancer diagnosis, available data fail to demonstrate that, once breast cancer has been diagnosed, estrogens worsen prognosis, accelerate the course of the disease, reduce survival or interfere with the management of breast cancer. It may therefore be concluded that the prevalent opinion that estrogens and estrogen treatment are deleterious for breast cancer, needs to be revisited. However, results of ongoing prospective, randomised clinical trials with different HRT regimens in healthy women or breast cancer survivors are needed to provide more definite conclusions about risks and benefits of HRT.

Elevated free androgen index as an indicator of polycystic ovaries in oligomenorrhoea without obesity or hirsuties.

A group of oligomenorrhoeic women without obesity or hirsuties was investigated with high-resolution ultrasound, laparoscopy and biochemical parameters. In this series, polycystic ovaries (PCO), as defined by ultrasound and laparoscopy, are a common cause of oligomenorrhoea in women without the classic symptoms, and were strongly associated with an elevated free androgen index (FAI). Despite an elevated FAI, these women were not hirsute, It would seem reasonable to include a FAI in the investigation of the oligomenorrhoeic woman, along with the more 'standard' tests, such as thyroid function and a prolactin level.

Factors influencing the free androgen index in a group of subfertile women with normal ovaries.

Eighty-five regularly cycling women with normal ovaries at laparoscopy, were studied to determine the factors that influence the free androgen index (FAI). It was found that body mass index (BMI), age of the patient and the phase of the menstrual cycle that the blood was collected can all affect the FAI. It is recommended that where possible, specimens should be collected in the early follicular phase to avoid misinterpretation of the result.

The effects of soy protein in women and men with elevated plasma lipids.

Fifty four postmenopausal women with elevated cholesterol were recruited for a randomised, double-blind controlled trial of soy protein containing isoflavones. (ISP+) or a soy protein with a low isoflavone content (ISP-), taken daily for 12 weeks. There was an overall reduction after 12 weeks in total cholesterol (TC), LDL cholesterol (LDL-C), sex hormone binding globulin (SHBG), and luteinizing hormone (LH). There were no significant differences between treatment groups. In a separate study 27 male subjects with a TC > 5.5 mmol/l were given ISP+ for 12 weeks. In this male study there was a significant increase in HDL cholesterol (HDL-C) and SHBG. Soy protein has a cholesterol lowering effect in both women and men. These studies suggest that this effect is independent of isoflavones. Soy protein also reduces SHBG levels in both sexes.

A double-blind, randomized, placebo-controlled trial of the effect of testosterone cream on the sexual motivation of menopausal hysterectomized women with hypoactive sexual desire disorder.

OBJECTIVES: To assess the safety and efficacy of 10 mg topical testosterone therapy daily (2 cm Andro-Feme cream) as a treatment for low sexual desire in postmenopausal hysterectomized women who were already on transdermal estrogen. METHODS: A double-blind, randomized, placebo-controlled, cross-over study (each period being of 3 months' duration) was performed in the research center of a tertiary referral women's hospital. Thirty-six menopausal healthy women were recruited who had undergone a hysterectomy, who were not depressed, were in a stable relationship and who fulfilled diagnostic criteria for low sexual desire, as measured by the Brief Index of Sexual Function for Women (BISF-W). MAIN OUTCOME MEASURES: The primary outcome measure was improvement in the sexuality score as measured by a validated tool (BISF-W); secondary measures were sub-scores of the BISF-W, effect on mood and energy, lipids and testosterone levels. RESULTS: Testosterone cream significantly improved sexual desire, frequency of sex, receptivity and initiation as measured by the BISF-W score. It did not change mood, energy, lipids, blood pressure or weight over the study period. CONCLUSIONS: Testosterone cream significantly improved sexual scores in menopausal women with low sexual desire. It was effective, easy to use and had no side-effects over the 3-month period of active treatment. It offers a novel and acceptable method of administering testosterone to menopausal women.

Which is the best test to detect the polycystic ovary?

Laparoscopy was used to characterize the ovaries of a group of infertile women. Patients with polycystic ovaries (PCO) were compared with those with normal ovaries. A free androgen index (FAI) greater than 4.5 was 100% specific and sensitive for detecting the PCO in a group of women with oligomenorrhoea. Overall, a biochemical 'screen' consisting of a luteinizing hormone (LH) level greater than 10 U/l, testosterone (T) greater 2.6 nmol/l, sex hormone binding globulin (SHBG) greater than 31 nmol/l or a FAI greater than 4.5 was 89% sensitive and 98% specific for PCO, which is comparable with the reliability of ultrasound for detecting the PCO.

Two cases of partial 21 hydroxylase deficiency associated with progesterone excess.

Two cases of partial 21 hydroxylase deficiency are presented where inappropriate follicular phase progesterone secretion was documented and ultrasonography demonstrated a failure of the normal endometrial and uterine growth towards ovulation.

The polycystic ovary syndrome presenting as resistant acne successfully treated with cyproterone acetate.

OBJECTIVE: To review a group of Australian women presenting to a reproductive endocrinologist with acne and investigate how many had androgen excess and how they had responded to endocrinological therapy. DESIGN: All patients referred to me over a 12 month period were included in the study and investigated in a standard manner. Medical therapy was given in a non-randomised manner based on clinical and biochemical evidence. SETTING: Most patients were referred to my private practice, but all public patients seen over this period were also included. PATIENTS: Subjects were women who presented with acne. Some were also hirsute and/or had menstrual irregularities. The total group consisted of 157 subjects. Patients with thyroid disease, hyperprolactinaemia, and late-onset congenital adrenal hyperplasia, and menopausal women were excluded, and the final study group consisted of 90 subjects. INTERVENTIONS: Women presenting with acne but no hirsutism and an elevated level of dehydroepiandrosterone sulphate were treated with low-dose dexamethasone. All other subjects were treated with ethinyloestradiol and cyproterone acetate. MAIN OUTCOME MEASURES: (i) The diagnosis of polycystic ovary syndrome and (ii) the effect of endocrinological therapy on their acne. RESULTS: Of the 90 subjects presenting with acne, 67 (74%) were found to have the polycystic ovary syndrome. In all cases the acne was substantially reduced by treatment. All 30 subjects who had previously failed to respond to standard dermatological preparations were successfully treated with combined ethinyloestradiol and cyproterone acetate therapy. CONCLUSIONS: The polycystic ovary syndrome is commonly found amongst women complaining of acne. Some patients will not have excess body hair, obesity or menstrual irregularities. Among women with resistant acne, not responding to conventional treatments, the polycystic ovary syndrome is very common. Treatment with ethinyloestradiol and cyproterone acetate is an extremely effective, safe and well tolerated therapy for these women.

Progestogens: an occasional review.

Progestogens are drugs which share the ability to stimulate the progesterone receptor, but differ in many other aspects. Some of their uses include the regulation of menstrual bleeding, protection of oestrogen-primed endometrium, contraception and as anticancer therapy. However, progesterone physical and psychological side-effects and potentially adverse metabolic effects including lipoprotein changes must be considered. An understanding of these differences will permit appropriate prescribing of these drugs for gynaecological and medical disorders.

Fetal-induced trauma as a cause of antepartum hemorrhage.

External trauma is a well-known cause of antepartum hemorrhage. These two cases demonstrate that fetal trauma may also be a cause of antepartum hemorrhage. Both patients complained of painful fetal movements, and real-time ultrasonography demonstrated that the fetus was striking the placental edge.

Managing the menopause: phyto-oestrogens or hormone replacement therapy?

Menopause is a natural event, and understandably many women would like to take a natural therapy rather than a drug for managing their menopause symptoms as well as preventing the long-term sequelae of oestrogen deficiency. In this respect phyto-oestrogens show a lot of promise. However, at this point in time clinical data are inconclusive. There are some data supporting the contention that isoflavones improve hot flushes; however, there are also negative studies. Soy protein has been shown to lower cholesterol, and isoflavones improve arterial compliance. Clinical studies suggest that isoflavones have little impact on menopause-induced bone loss.