An retrospective audit of patients with polycystic ovary syndrome: the effects of a reduced glycaemic load diet.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and chronic anovulation. The aim of this retrospective audit was to determine the patient profile, including anthropometrics, biochemistry and symptoms, and to evaluate the influence of a dietary intervention in women with PCOS. METHODS: Data were collected retrospectively from dietetic and medical records from all PCOS patients (n = 88) who attended a dietetic consultation from July 2004 to July 2006. As standard clinic practice, a reduced glycaemic load diet had been prescribed, with energy reduction in overweight patients. Follow-up data were available for 59 patients. RESULTS: Fifty-eight patients had a body mass index (BMI) or= 25 kg m(-2). Thirty-six patients, with a BMI

Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis.

In a randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover over a period of 2 years. Our study comprised 117 Caucasian postmenopausal women, otherwise healthy apart from reduced bone density. They received either intranasal synthetic SCT (200 IU either three times weekly or daily) or placebo. Compared with placebo, daily intranasal calcitonin resulted in no significant bone loss in the lumbar spine, as assessed by dual photon absorptiometry, over the 2-year study period (P < 0.02). In this group, women more than 5 years postmenopause, with the lowest baseline bone mass, showed the greatest response to this treatment, with a total increase placebo in lumbar spine BMD of 3.1%. Significant spinal bone loss (P < 0.005) occurred in women receiving either placebo or thrice-weekly calcitonin. Although the rates of bone loss in the proximal femur were not significantly different in the three groups, there were differences over time. Whereas bone loss in the daily calcitonin group was insignificant, women who received placebo or thrice-weekly calcitonin experienced significant bone loss (P < 0. 001). No significant changes in biochemical markers were observed in any group. Therapy was well tolerated and there were no significant treatment-related adverse events. We conclude that intranasal SCT 200 IU daily is effective and safe for the prevention of bone loss in postmenopausal women with reduced bone mass.

Long-term effects of transdermal and oral hormone replacement therapy on postmenopausal bone loss.

Transdermal hormone replacement therapy (HRT) is now an accepted form of treatment, but the long-term skeletal effects have not been assessed. Sixty-six early postmenopausal women were randomized to receive either transdermal HRT (continuous 17 beta-oestradiol 0.05 mg/day, with 0.25 mg/day of norethisterone acetate added for 14 days of each 28-day cycle) or oral HRT (continuous conjugated equine oestrogens 0.625 mg/day, with 0.15 mg/day dl-norgestrel added for 12 days of each 28-day cycle). Treatment was given for 3 years and 30 matched untreated women were studied concurrently as a control group. Bone density was measured in the lumbar spine and proximal femur by dual-photon absorptiometry at 6-monthly intervals. Bone turnover was assessed by measurement of biochemical markers. At 3 years bone density had declined by 4% in the lumbar spine and by more than 5% in the femoral neck in the untreated group. By comparison bone density increased in both treatment groups at both sites (p < 0.001 vs. untreated) and biochemical measurements indicated a significant reduction in bone turnover. There were no significant differences between the treatment groups. Twelve per cent of women on transdermal or oral treatments lost a significant amount of bone from the femoral neck by 3 years despite adequate compliance. Women taking therapy primarily for hip fracture prevention may require a follow-up bone density measurement to establish the efficacy of treatment.

Long-term effects of oral and transdermal hormone replacement therapies on serum lipid and lipoprotein concentrations.

OBJECTIVE: To see whether the short-term changes in serum lipid and lipoprotein concentrations induced by postmenopausal estrogen-progestin therapy are maintained in the long term. METHODS: Sixty-one healthy postmenopausal women were randomized to either oral therapy (continuous conjugated equine estrogens at 0.625 mg/day with sequential dl-norgestrel at 0.15 mg/day for 12 days each cycle) or transdermal therapy (patches delivering continuous 17 beta-estradiol [E2] at 0.05 mg/day with sequential norethindrone acetate at 0.25 mg/day for 14 days each cycle). Twenty-nine healthy postmenopausal women who did not request therapy served as a reference group. Fasting serum lipid and lipoprotein concentrations were monitored for 3 years. RESULTS: Studied in the estrogen-progestin phase, oral and transdermal therapies reduced serum total cholesterol concentrations by 12.1% (P < .001) and 8.4% (P < .001), respectively, and those of low-density lipoprotein (LDL) by 14.2% (P < .001) and 6.6% (P < .01), respectively. These changes, apparent at 3 months, were maintained over 3 years. Serum triglyceride concentrations fell by 2.5% (P < .05) and 16.4% (P < .01), respectively. These decreases were evident after 6 months in both groups but were maintained over 3 years only in the transdermal group. High-density lipoprotein (HDL) concentrations fell in women given oral therapy (7.8%, P < .05) and transdermal therapy (10.7%, P < .001), as well as in untreated women (7.0%, P < .05). CONCLUSIONS: The potentially beneficial effects of estrogen-progestin therapy on serum total and LDL cholesterol and on triglycerides were maintained over 3 years. Interpretation of the potentially detrimental effects on HDL concentrations was hindered by the changes seen in untreated women.

Paradoxical effects of hormone replacement therapy on breast tenderness in postmenopausal women.

We have studied the effect of HRT on breast tenderness in 61 postmenopausal women randomised to oral or transdermal sequential HRT. An untreated reference group of 29 postmenopausal women was studied concurrently. A questionnaire concerning breast tenderness was administered before and after 10, 12 and 24 weeks of treatment (n = 60) and on 3 occasions at 3-month intervals in the reference group (n = 28). In 10 women with frequent tenderness at baseline, HRT resulted in a reduction at 10 weeks (P < 0.05), which was maintained at 24 weeks (P < 0.05). In contrast, 10 women with infrequent tenderness before treatment reported worsening of tenderness at the 10-week visit (P < 0.01 for transdermal, P < 0.05 for oral), which was not significantly different from the baseline thereafter. These 10 women were older (P < 0.05), and further from the menopause (P < 0.05) than the remaining 40 women who did not develop more frequent tenderness. No significant changes occurred in the reference group. HRT may cause transient breast tenderness, especially in older women and those furthest from the menopause. Paradoxically, it may relieve this symptom in women who have breast tenderness prior to treatment. Breast tenderness should not be considered a contraindication to HRT.

Effect of continuous combined estrogen and desogestrel hormone replacement therapy on serum lipids and lipoproteins.

OBJECTIVE: To determine the effects of continuous combined hormone replacement therapy with desogestrel and 17 beta-estradiol (E2) on serum lipids and lipoproteins. METHODS: Fifty-seven healthy postmenopausal women of less than 60 years of age were studied prospectively and treated with oral desogestrel 0.15 mg/day and micronized 17 beta-E2 1 mg/day, both taken continuously. Fasting venous blood samples for serum lipids and lipoproteins were taken before and after 6 and 12 months of treatment. RESULTS: Thirty-two women completed the study. Levels of all serum lipids and lipoproteins fell significantly by 6 months and remained low at 12 months. The mean percentage reduction after 12 months of treatment was 12.8% for high-density lipoprotein (HDL) cholesterol, which largely resulted from a reduction in the HDL2 subfraction, which fell by 25.7%. The mean percentage reduction for both low-density lipoprotein (LDL) cholesterol and triglycerides was 7.7%. The median percentage reduction for lipoprotein (a) was 17.6%. CONCLUSIONS: This combination of hormone replacement therapy had profound effects on serum lipids and lipoproteins. According to current concepts, reductions in total and LDL cholesterol, triglycerides, and lipoprotein (a) may reduce cardiovascular disease risk. The reduction in HDL was unexpected, given the rise in HDL that has been demonstrated when desogestrel is combined with ethinyl estradiol in the contraceptive pill. The lowering of HDL observed in this study is undesirable and may be potentially harmful. Our results indicate that when desogestrel 0.15 mg/day is combined with micronized 17 beta-E2 1 mg/day in a continuous manner, the effects of the progestogen on HDL predominate and cause a reduction in HDL and the HDL2 subfraction.

Postmenopausal bone loss: does HRT always work?

In a 3-year study comparing oral and transdermal HRT, we measured bone density in the spine and proximal femur by dual-photon absorptiometry. Sixty-six women were randomly allocated to receive either oral conjugated equine oestrogens, 0.625 mg daily, together with cyclical oral dl-norgestrel, 0.15 mg daily, or transdermal 17 beta-oestradiol, 0.05 mg daily, together with cyclical transdermal norethisterone acetate, 0.25 mg daily. We found that only 2% showed significant vertebral bone loss on either treatment, whilst approximately 12% lost from the proximal femur. Compliance was demonstrated by monitoring all used patches and pill packets, recording all side effects and bleeding patterns, and by the demonstration of appropriate changes in levels of gonadal steroids and lipoproteins. Comparing the bone losers with the ten highest gainers, lowers were closer to their menopause but were not different in body mass or life style. Serum oestradiol levels were similar, and both groups showed a similar response in terms of changes in bone biochemical markers and lipoproteins in response to HRT. In thus seems that a small proportion of women do not conserve bone density in the proximal femur with standard doses of HRT. It remains to be determined whether they could be identified by more specific biochemical markers of bone turnover, and whether they would maintain with a higher dose of oestrogen.

HRT: developments in therapy.

Various forms of oestrogen have been available for use as Hormone Replacement Therapy (HRT) for approximately 50 years. However, there has been little change in the mode of administration until the last 10-15 years. Although the oral route has remained the mainstay of therapy, non-oral routes of administration have been developed. During the 1970s it became clear that use of unopposed oestrogens in women with an intact uterus resulted in an increase in risk of endometrial carcinoma and thus the current practice of adding a sequential progestogen each month, to prevent endometrial hyperplasia, was introduced. However, certain progestogens can cause side-effects and some of the metabolic changes which they induce are potentially undesirable. Thus the search continues for new oral progestogens which are more 'metabolically friendly' than those in current use. Additionally, non-oral delivery systems for progestogens have been studied, such as the transdermal route (patches) and local administration within the uterine cavity (progestogen-containing intra-uterine devices). Both these strategies may minimise their symptomatic, psychological and metabolic effects. Continuous (every day) administration of progestogens in combination with the oestrogen, or the use of new compounds (e.g. tibolone) may overcome the problem of regular withdrawal bleeding which some women find unacceptable. However, it remains to be determined whether such therapies are as efficacious as conventional oestrogen/sequential progesterone regimens.

Riesgos y beneficios a largo plazo de la terapia mediante substitución de hormonas / Risks and benefits of long term of the therapy by hormone replacement

Existe un consenso en cuanto a que las consecuencias a largo plazo de la deprivación ovárica pueden ser prevenidas o reducidas mediante una terapia de substitución hormomal (TSH). Después de la menopausia, se produce una pérdida rápida del hueso trabecular que en uno de casa dos casos resulta en riesgo de por vida de fracturas osteoporósicas. La terapia de substitución hormonal (TSH) previene, esta pérdida del hueso y disminuye la incidencia de fracturas. Se recomienda un mínimo de 5 años de tratamiento para lograr beneficios significativos. La evidencia epidemiológica viene acumulándose en cuanto a que la terapia de estrógenos postmenopáusica reduce el riego de enfermedades cardiovasculares y de apoplejías en cerca de 30% y 70%, aún en presencia de factores de riesgo establecidos. Dada la frecuencia de enfermedades cardiovasculares, ésta viene a ser probablemente una de las ventajas originales de la terapia mediante substitución de hormonas en la próxima década. Las inquietudes acerca de la seguridad a largo plazo de la TSH se han concentrado en el cáncer endometrial y de la mama. El incremento del riesgo de cáncer de endometrio asociado con a terapia única con estrógenos es disminuida con la adición secuencia de progesterona por 10 a 12 días en cada ciclo. El posible efecto de la terapia (TSH) en cuanto a riesgo de cáncer de mama debe ser considerado frente a experiencias que indica que uno de cada 12 desarrolla esta enfermedad. Los estudios epidemiológicos que investigan esta relación son revisados en este trabajo. Existe un gram consenso en que la terapia mediante substitución de hormonas (TSH) con una duración de 5 a 6 años no incrementa los riesgos de cáncer de mama. Terapias de mayor duración (10-15 años) se han reportado, que incrementan este riesgo, pese a que no toda la información es conforme. Otros factores, tales como la historia familiar y las enfermedades benignas de mama, también podrían influir en los riesgos de cáncer...

Changes in body composition with danazol therapy.

Whole body lean and fat mass measurements by dual energy x-ray absorptiometry were performed in 14 premenopausal women undergoing danazol treatment for endometriosis. After 6 months, there was a significant increase in lean tissue mass. Body fat decreased but this was significantly less in the android (upper body segment) region than in the gynoid (lower body segment) region. Danazol thus has both anabolic and androgenic effects on body composition. Dual energy x-ray absorptiometry provides a new, noninvasive, and rapid means of studying body composition.

The long-term risks and benefits of hormone replacement therapy.

There is increasing awareness that the long-term consequences of ovarian failure can be prevented or reduced with appropriate hormone replacement therapy (HRT). After the menopause, there is a rapid loss of trabecular bone resulting in a one in two lifetime risk of osteoporotic fracture. HRT prevents this bone loss and decreases the incidence of fracture. A minimum of 5 years treatment is recommended for significant benefit. Epidemiological evidence is accumulating that post-menopausal oestrogen therapy reduces the risk of cardiovascular disease and stroke by between 30 and 70% even in the presence of established risk factors. Given the prevalence of cardiovascular disease, this is likely to be one of the principle benefits of HRT in the next decade. Concerns about the long-term safety of HRT have focused on endometrial and breast cancer. The increase in risk of endometrial cancer associated with oestrogen only therapy is abolished with the sequential addition of a progestogen for 10-12 days each cycle. The possible effect of HRT on breast cancer risk has to be considered against the background of a one in 12 lifetime risk of developing this disease. The epidemiological studies investigating this relationship are reviewed in this paper. There is a broad consensus that 5-6 years duration of HRT does not increase breast cancer risk. Longer durations of therapy (10-15 years) have been reported to increase this risk although not all the data are in agreement. Other factors, such as family history and benign breast disease, may also influence the risk of breast cancer. The potential benefits of HRT on mortality and morbidity are enormous. Against this is a possible small increase in breast cancer risk with long-term usage. Greater awareness of the long term consequences of the menopause and the potential benefits of HRT should be encouraged so that women can make informed decisions about their need for HRT.