D.M. Hart

Urogenital ageing and its effect on sexual health in older British women

Objective To provide information on the extent of problems of urogenital ageing in older British women.

Bone loss during oestriol therapy in postmenopausal women.

In contrast to all other oestrogens examined thus far oestriol hemisuccinate (12 mg/day) did not prevent bone loss in 28 postmenopausal women. The average bone loss, however, was somewhat less than expected from placebo studies, while the bone loss achieved by a group taking 4-6 mg/day was equal to that achieved by previous placebo groups. To be an effective agent for prevention of post-menopausal osteoporosis oestriol would have to be prescribed in daily doses considerably in excess of 12 mg.

CALCITONIN AND POSTMENOPAUSAL OSTEOPOROSIS

Fasting serum calcitonin levels were measured in 54 postmenopausal women who had for 10 years been taking part in a double blind trial to assess the effect of the synthetic oestrogen, mestranol, on postmenopausal bone loss. There were no differences in calcitonin levels between mestranol treated and placebo groups, Fifteen of the women were challenged with a calcium infusion to measure the secretory reserve of calcitonin. Oestrogen treatment did not increase the calcitonin response to calcium infusion. The three patients who exhibited the greatest responses were placebo treated. Bone density was measured by γ‐ray absorptiometry over the ten year period and the annual rate of change of bone density calculated. No correlation could be found between basal calcitonin level or calcitonin reserve and change in bone density. Our results indicate that postmenopausal osteoporosis is not caused by a deficiency of calcitonin and that the action of oestrogen therapy to prevent bone loss does not involve calcitonin.

Response of plasma low density lipoprotein subfractions to oestrogen replacement therapy following surgical menopause

OBJECTIVE Epidemiological studies suggest that postmenopausal oestrogen replacement reduces the incidence of cardiovascular disease. The purpose of this study was to establish the effects of oestrogen replacement therapy on subfractions of plasma low density lipoprotein in bilaterally oophorectomized women.

Failure of response of menopausal vasomotor symptoms to clonidine

A double-blind crossover trial of clonidine failed to show any effect of the drug on menopausal vasomotor symptoms. A significant placebo effect was observed, the effect being greater in those with long-standing symptoms and a high neurotic index.

The effect of endogenous oestrogen on plasma and urinary calcium and phosphate in oophorectomized women.

Using a specific radioimmunoassay, significant levels of plasma oestradiol can be detected in the blood of oophorectomized women. In these women the plasma concentration of oestradiol correlates positively with the body fat content. Low circulating concentrations of oestradiol are associated with increased values for serum phosphate and alkaline phosphatase, but no significant change in serum calcium. The fasting urinary calcium creatinine ratio is inversely related to circulating plasma oestradiol concentration which also correlates, in a more complex way, with the renal threshold for phosphate (TmPO4/GFR). It is suggested that oestrogen production may be an important factor in determining bone loss in post‐menopausal women.

Effects of bilateral oophorectomy on lipoprotein metabolism

Summary. The effects of surgical menopause on lipoprotein levels and their dme course were studied in 31 premenopausal women who were undergoing hysterectomy and bilateral oophorectomy for non‐malignant conditions. Lipoprotein levels were measured beforc oophorectomy and afterwards at 6 and 12 weeks, then at intervals of 3 months for 18 months. Low density lipoprotein (LDL) cholesterol levels rose significantly (P<0.05) in the 6 weeks after operation from a mean of 3.57 (SD 0.66) mmol/1 to 4.21 (SD 0.84) mmol/1 with no significant changes thereafter. There were no significant changes in cholesterol in the other density fractions or in triglyceride levels. High density lipoprotein (HDL) subfractions were measured in 10 of the women to assess any change in the relative amounts of cholesterol carried on HDL2 and HDL3, since the protective effect of HDL is believed to be conferred by the HDL2 fraction only. No significant change was found in either fraction. The increase in LDL cholesterol would be expected to result in an appreciable increase in the risk of developing coronary heart disease, but cannot wholly account for the increase in cardiovascular disease associated with oophorectomy.

Assessment of synthetic steroid (Org OD 14): Effect on skeletal metabolism by 24-h whole-body retention of diphosphonate

Using a 24-h whole-body retention (WBR) of Tc99m hydroxyethylidene diphosphonate (HEDP), a sensitive measure of skeletal metabolism, 24 women receiving the synthetic steroid hormone Org OD 14 were studied. OD 14 was found to have a powerful suppressive effect on skeletal metabolism in both oophorectomized and non-oophorectomized women when compared with control subjects (P less than 0.001 and P less than 0.01, respectively). The degree of suppression was similar to that found with oestrogen therapy. While it has previously been shown that OD 14 prevents bone mineral loss (as measured by photon-absorptiometry), the present study provides further evidence as to the efficacy of this compound in suppressing skeletal metabolism.

A comparison of the effects of two continuous HRT regimens on cardiovascular risk factors

In a study comparing the effects of two continuous HRT regimens on cardiovascular risk markers, 43 postmenopausal women were randomly assigned to receive either tibolone 2.5 mg/day (n=20) or 0.625 mg/day conjugated equine oestrogens plus continuous medroxyprogesterone acetate 5 mg/day (n=23). Serum lipoprotein levels, including LDL and HDL subfractions, oxidisability of LDL and serum nitrate/nitrite levels were determined before and during 12 weeks of therapy. Tibolone significantly reduced triglycerides (17.1%, P<0.01), HDL cholesterol (22.2%, P<0.001), and the ratio HDL(2)/HDL(3) cholesterol (20.2%, P<0.01). Total LDL cholesterol levels did not change significantly, although there was a downward trend in the LDLIII subfraction (12.0% reduction; P=0.06), percentage changes being positively correlated with percentage changes in triglyceride levels (r=0.60, P<0.01). Susceptibility of LDL to oxidation was significantly decreased (P<0.001), changes in lag-time being highly negatively correlated with percentage changes in levels of both LDLIII (r=-0.68, P<0.01) and triglycerides (r=-0.63, P<0.01). Nitrate/nitrite levels did not change. In contrast, the combined therapy caused a significant reduction in LDL cholesterol levels (11.1%; P<0.01) as a result of a significant decrease in the LDLI+II subfraction (12.8%; P<0.05). Changes in LDLI+II and LDLIII were correlated with changes in triglyceride levels (r=-0.52, P<0.05 and r=0.63, P<0.01, respectively). No other parameter was significantly modified. Between treatment effects were significantly different on triglycerides (P<0.01), HDL cholesterol (P<0.001), LDL oxidation (P<0.01) and LDLI+II:LDLIII ratio (P<0.05). The reduction in LDL induced by the continuous combined therapy is likely to be beneficial, despite the apparent shift towards the LDLIII subfraction. Changes in oxidisability and subfraction profile of LDL indicate that tibolone may have a more favourable effect on cardiovascular risk than previously suggested.

Org OD 14: long-term effects on serum lipoproteins

For many years oestrogen replacement therapy has been used to relieve climacteric symptoms and prevent the loss of bone that occurs after the menopause. However, oestrogen treatment can lead to endometrial hyperplasia [l] unless it is given with a progestogen, which brings with it the inconvenience of monthly uterine bleedings. In addition, most progestogens have adverse effects on lipoprotein metabolism [2,3]. Org OD 14, a synthetic steroid[(7a, 17cu)-17-hydroxy-7-methyl-l9-norpregn-5(10)en-20-yn-3-one], has been shown to be effective in alleviating climacteric symptoms and preventing post-menopausal osteoporosis and to have no stimulatory effect on the endometrium [4,5]. The steroid has been shown in animal experiments to have a combination of weak oestrogenic, androgenic and progestogenic activities (research files, Organon International, Oss, The Netherlands). Its long-term effects on lipoprotein metabolism have not been reported. We have measured lipoprotein levels in 24 post-menopausal women who had been taking Org OD 14 for a period of 5 yr and compared them with those of a control group.