Continuing decline in hormone therapy use: population trends over 17 years.

OBJECTIVE: To describe the prevalence of menopausal hormone therapy (HT) in 2008 and trends over the last 17 years in an Australian population. METHODS: Data were obtained from nine representative population face-to-face interview surveys of the South Australian population from 1991 to 2008. The surveys used consistent method and quality control procedures. In 2008, demographic data, HT use and eight dimensions of health, using the SF-36 health survey questionnaire, were measured. Participants Over 3000 South Australian adults were interviewed in their own home by trained health interviewers in each of the surveys; in the 2008 survey, 1555 women participated, of whom 953 were over age 40. RESULTS: After a peak in use in the 2000 survey, HT use fell from 2003 and has continued to decline in 2008. In 2008, current use over age 50 of registered conventional HT products is now 11.8%, with a further 4.0% using non-registered alternative 'hormonal' products. Current HT use is highest between the ages of 50 and 59 years, where 13.4% use conventional HT and 7.7% use unconventional alternative hormones. Use of these unregistered hormonal products was rare in previous surveys. Median and mean length of conventional HT use were 10.0 and 10.5 years, respectively. HT users continued to have a demographic profile similar to those in previous surveys, i.e. they were better educated, employed, partnered, had a higher income and were less inclined to use complementary and alternative medicines. CONCLUSIONS: There has been a continuing decline in both the overall prevalence and length of use of conventional HT from 2003, probably in association with negative media about HT. Of medical concern is that about one-quarter of women using HT around menopause now chooses unregistered hormonal mixtures that are untested for long-term safety and efficacy.

Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes.

BACKGROUND: Hot flushes and night sweats are common symptoms experienced by menopausal women. Hormone therapy (HT), containing oestrogens alone or oestrogens together with progestogens in a cyclic or continuous regimen, is often recommended for their alleviation. OBJECTIVES: To examine the effect of oral HT compared to placebo on these vasomotor symptoms and the risk of early onset side-effects. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders Group and Subfertility Group trials register (searched May 2002). This register is based on regular searches of MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, the handsearching of 20 relevant journals and conference proceedings, and searches of several key grey literature sources. We also contacted all relevant pharmaceutical companies, The Journal of the International Menopause Society and Climacteric. SELECTION CRITERIA: Double-blind, randomised, placebo-controlled trials of oral HT for at least three months duration. DATA COLLECTION AND ANALYSIS: Study quality and outcome data were assessed independently. Random effects models were considered appropriate due to the variety of trial methodologies. The meta-analyses were explored for sensitivity to trial quality and therapy duration. Symptom frequency and severity were assessed separately, together with withdrawals and side-effects. Frequency data were analysed using the Weighted Mean Difference (WMD) between treatment and placebo outcomes. For severity data, odds ratios were estimated from the proportional odds model. From 115 references originally identified, 24 trials meeting the selection criteria were included in the review. Study participants totaled 3,329. Trial duration ranged from three months to three years. MAIN RESULTS: There was a significant reduction in the weekly hot flush frequency for HT compared to placebo (WMD -17.92, 95% CI -22.86 to -12.99). This was equivalent to a 75% reduction in frequency (95% CI 64.3 to 82.3) for HT relative to placebo. Symptom severity was also significantly reduced compared to placebo (OR 0.13, 95% CI 0.07 to 0.23). Withdrawal for lack of efficacy occurred significantly more often on placebo therapy (OR 10.51, 95% CI 5.00 to 22.09). Withdrawal for adverse events, commonly breast tenderness, oedema, joint pain and psychological symptoms, was not significantly increased (OR 1.25, 95% CI 0.83 to 1.90), although the occurrence of any adverse events was significantly increased for HT (OR 1.41, 95% CI 1.00 to 1.99). In women who were randomised to placebo treatment, a 57.7% (95% CI 45.1 to 67.7) reduction in hot flushes was observed between baseline and end of study. REVIEWERS' CONCLUSIONS: Oral HT is highly effective in alleviating hot flushes and night sweats. Therapies purported to reduce such symptoms must be assessed in blinded trials against a placebo or a validated therapy because of the large placebo effect seen in well conducted randomised controlled trials, and also because during menopause symptoms may fluctuate and after menopause symptoms often decline. Withdrawals due to side-effects were only marginally increased in the HT groups despite the inability to tailor HT in these fixed dose trials. Comparisons of hormonal doses, product types or regimens require analysis of trials with these specific "within study" comparisons.

Genistein inhibits growth of B16 melanoma cells in vivo and in vitro and promotes differentiation in vitro.

Consumption of soy products has been linked to a reduced mortality and morbidity from a number of cancers. Genistein, one of the principal soy isoflavones, has been shown to inhibit the growth of a number of tumour cell lines in vitro; however, a role of genistein in retarding tumour growth in vivo is less well documented. In this study, in addition to examining the effects of genistein on the growth of murine B16 melanoma cells in vitro, we have examined the effects of feeding a genistein-rich diet on s.c. growth of these tumour cells in mice. In vitro, the melanoma cells showed an increase in sensitivity to genistein with increasing time of exposure, culminating in a 50% growth inhibition (IC50) at 12.5 microM after 7 days. Genistein at 25 microM induced micronucleus formation after 24 hr and at concentrations as low as 2.5 microM induced morphological changes indicative of differentiation. Growth of solid tumours implanted into female C57BL/6J mice was inhibited by 50% when mice were fed genistein for 1 week before and for 1 week after inoculation with B16 melanoma cells. Plasma genistein concentrations at the time of tumour removal were 1.1 microM, which is similar to levels reported in humans consuming diets high in soybeans or soybean products, while control animals had no detectable genistein in plasma. Our results provide additional in vivo evidence suggesting that genistein retards the growth of implanted tumours, adding further to studies suggesting that this isoflavonoid is a biologically active component of soy foods.

Absorption and excretion of the soy isoflavone genistein in rats.

Rodent models have been used to study the anticarcinogenic properties of the soy isoflavones, particularly genistein, but there is little information regarding the pharmacokinetics of the absorption and excretion of genistein. In this study, rats were given a single oral dose of genistein (20 mg/kg body weight) or an equivalent dose of its glycone forms, as an isoflavone-rich soy extract. Concentrations of genistein were measured in plasma, urine and feces at intervals up to 48 h after dosing. Plasma genistein concentration at 2 h after dosing was 11.0 +/- 2.3 mumol/L in genistein-treated rats compared with 4.93 +/- 0.22 mumol/L (P = 0.025) in soy extract-treated rats, but there were no significant differences at 8 h and later times. The mean urinary excretion rate during the first 2 h after dosing was more than 10 times higher in the genistein group compared with the soy extract group (0.27 +/- 0.08 mumol/h and 0.020 +/- 0.011 mumol/h, respectively, P = 0.017) but the percentage of dose recovered in urine over 48 h was not different between groups (19.9 +/- 2.4% genistein treated; 17.5 +/- 1.1% soy extract treated). There were no significant differences between groups in the recovery of genistein in feces (21.9 +/- 2.8% and 21.1 +/- 2.5% of dose, respectively). Only 6.1 +/- 0.9% of the daidzein from the soy extract was recovered in the feces. The results suggest that the extent of absorption of genistein is similar for the glycone and aglycone forms. Although higher initial plasma concentrations may be achieved with the aglycone, similar long-term concentrations exist for both forms of isoflavone.