Kevin F. Gangar

Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause

The protection afforded by postmenopausal oestrogen replacement against cardiovascular disease is not fully explained by changes in plasma lipoproteins. To investigate the effect of oestrogen on arterial tone, Doppler ultrasound was used to assess blood flow characteristics in the internal carotid arteries of 12 postmenopausal women. Patients were studied pretreatment and at weeks 4, 6, 9, and 22 of therapy with transdermal oestradiol 50 micrograms/day. The pulsatility index (PI), which is thought to represent impedance to blood flow distal to the point of sampling, was measured from the flow velocity waveform. 11 of the 12 patients were within 5 years of menopause; 1 was 8 years postmenopausal but had experienced bleeding 4 years after menopause. In the 11 women there was a highly significant correlation (r = 0.77) between time since menopause and baseline PI. A similar correlation (r = 0.74) was observed when the episode of postmenopausal bleeding was redefined as time of menopause in the twelfth patient. For all 12 patients, there was a significant negative correlation (r = -0.70) between change in PI during transdermal oestradiol therapy and mean of baseline plus week 22 PI value. For all correlations between changes in PI and time since menopause, the longer the time the greater the fall in PI. These results, and previous observations of a reduction in uterine artery PI with oestradiol treatment, suggest that oestrogen has a generalised effect on the arterial system.

Effects of transdermal versus oral hormone replacement therapy on bone density in spine and proximal femur in postmenopausal women

66 early postmenopausal women were randomised to 28-day cycles of either transdermal hormone replacement therapy--continuous oestradiol 17-beta 0.05 mg daily, with norethisterone acetate 0.25 mg daily for 14 of each 28 days--or oral therapy--continuous conjugated equine oestrogens 0.625 mg daily, with dl-norgestrel 0.15 mg daily for 12 of each 28 days. An untreated reference group of 30 women were studied concurrently. Bone density was measured in the lumbar spine and proximal femur by dual photon absorptiometry at 6-month intervals for 18 months. Skeletal turnover was assessed by serum measurements of calcium, phosphate, and alkaline phosphatase, and by urine estimations of hydroxyproline/creatinine and calcium/creatinine excretion. In both treatment groups by comparison with the untreated groups by comparison with the untreated group, bone density increased in the vertebrae and proximal femur and biochemical measurements indicated a significant reduction in bone turnover.

Insulin resistance, secretion, and elimination in postmenopausal women receiving oral or transdermal hormone replacement therapy

Estrogen/progestin steroid combinations adversely affect glucose tolerance and insulin resistance, but their effects in combined hormone replacement therapy (HRT) have rarely been evaluated. We studied 61 untreated symptomatic postmenopausal women randomized to receive oral (conjugated equine estrogens, 0.625 mg/d continuous + levonorgestrel, 0.075 mg/d for 12 days of each 28-day cycle) or transdermal therapy (estradiol 17 beta, 0.05 mg/d continuous + norethindrone acetate, 0.25 mg/d for 14 days of each 28-day cycle). An untreated control group of 30 postmenopausal women not seeking HRT was also studied. Intravenous glucose tolerance tests (IVGTT) were performed at baseline and 3, 6, and 18 months later. Mathematical modeling analysis of plasma glucose, insulin, and C-peptide concentration profiles provided measures of insulin resistance, secretion, and elimination. There were no changes in glucose or insulin concentrations with transdermal therapy. Oral therapy caused a deterioration of glucose tolerance and an increased overall plasma insulin response, apparently due to a reduction in the immediate plasma insulin response to glucose. This may have resulted from increased hepatic insulin uptake, uncompensated for by an increase in first-phase pancreatic insulin secretion. Neither treatment caused significant insulin resistance compared with baseline, but with the oral treatment insulin resistance was greater during the combined phase compared with the estrogen-only phase. Thus the oral regimen affected both insulin delivery and insulin resistance. The transdermal regimen had relatively few effects on insulin metabolism.

Comparison of transdermal and oral estrogen-progestin replacement therapy: Effects on serum lipids and lipoproteins*‡

OBJECTIVE We attempted to ascertain whether transdermal postmenopausal estrogen-progestin therapy has the typical effects of oral therapy on serum lipoprotein risk markers for cardiovascular disease. STUDY DESIGN Sixty-one postmenopausal women were randomized to receive either transdermal continuous 17 beta-estradiol, 0.05 mg/day, with transdermal cyclic norethindrone acetate, 0.25 mg/day, or oral continuous conjugated equine estrogens, 0.625 mg/day, with oral cyclic dl-norgestrel, 0.15 mg/day. Twenty-nine untreated subjects served as controls. Lipoprotein profiles at 3 and 6 months were compared with baseline values by means of analysis of variance. RESULTS In the estrogen-alone phase both therapies reduced serum levels of total and low-density lipoprotein cholesterol; high-density lipoproteins were largely unchanged. Oral therapy increased triglycerides whereas this lipid fell with transdermal therapy. In the combined phase of the cycle both therapies reduced triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. CONCLUSION Transdermal and oral therapies had similar effects on lipoprotein cholesterol but different effects on triglycerides.

A Risk-Benefit Assessment of Estrogen Therapy in Postmenopausal Women

SummaryEstrogen therapy is extremely effective in relieving menopausal symptoms such as hot flushes, night sweats, urogenital atrophy and certain psychological symptoms. The short term side effects from this therapy are usually mild and self-limiting. They are more common in women who commence hormone replacement therapy some years after the menopause than in those who start treatment at about the time of the ovarian failure. Pre-existing gynaecological conditions such as fibroids and endometriosis can be worsened by estrogen therapy.The majority of published studies suggest a beneficial effect of postmenopausal estrogen therapy on cardiovascular and cerebrovascular disease. These effects may be mediated by favourable changes in lipids, but other mechanisms may also be involved. It is uncertain whether the adverse changes in lipids caused by progestogen therapy will reduce any of the benefits of estrogen therapy on the cardiovascular system.Osteoporosis is the major bone disease of the Western world; long term estrogen therapy will prevent its development in most postmenopausal women.The risk of endometrial carcinoma is increased with unopposed estrogen therapy; this increased risk appears to be abolished if a progestogen is added at an adequate dose and duration for each cycle. The risk of ovarian or cervical cancer is not increased with estrogen therapy. There may be an increased risk of breast carcinoma with long term postmenopausal estrogen use, but the studies show inconsistent results.

Oestrogen deficiency and oestradiol implants.

SIR,-Not only is the number of patients being treated in hospital increasing but it is thought that treatment is becoming more intensive. It has been my impression that this is throwing a considerable burden on junior staff. I have obtained data on the number of intravenous cannulas supplied annually over the past eight years to the two adjacent health districts of Dudley and Sandwell, serving a population totalling 500 000 (table).