Ultra low-dose hormone replacement therapy and bone protection in postmenopausal women.

OBJECTIVES: The aim of the present study was to evaluate the effects of low doses of hormone replacement therapy (HRT) in normal young postmenopausal women. METHODS: In an open trial healthy, non-obese postmenopausal women received for 2 years a low-dose continuous combined HRT (LD-HRT) containing 1mg estradiol+0.5 mg norethisterone acetate each pill for 28 days, or 0.5 mg of 17beta-estradiol and 0.25 mg of norethisterone acetate (Ultra low dose, Ultra-LD-HRT) along with 1000 mg of calcium per day. Control group consisted of women receiving only 1000 mg of calcium per day, for 2 years. Menopausal symptoms were evaluated by the Green climacteric scale for the first 12 weeks of the study while bleeding profiles, bone mineral density (BMD) and bone turnover were assessed for 24 months. RESULTS: LD-HRT and Ultra-LD-HRT were effective in reducing menopausal clinical symptoms. In the control group, BMD significantly (P<0.05) decreased at the spine (-2.8+/-0.2%), and femoral neck (-2.8+/-0.7%). In LD-HRT treated group BMD showed a significant (P<0.05) increase at the spine (5.2+/-0.7%), and femoral neck (2.8+/-0.4%) after 24 months. In the Ultra-LD-HRT treated women spine and femoral neck BMD showed a significant (P<0.05) increase (2.0+/-0.3 and 1.8+/-0.3%, respectively) after 24 months. In these women treated with LD-HRT and Ultra-LD-HRT the BMD values were significantly (P<0.05) different from those measured in calcium-treated women. CONCLUSIONS: LD-HRT and Ultra-LD-HRT can alleviate subjective symptoms providing an effective protection against the postmenopausal decrease of BMD.

Longitudinal evaluation of perimenopausal bone loss: effects of different low dose oral contraceptive preparations on bone mineral density.

OBJECTIVES: To evaluate the pattern of mineral density in eumenorrhoic and oligomenorrhoic perimenopausal women, and assess the effects of different low dose oral contraceptives (OC) on bone metabolism and spine bone density. METHODS: Spine bone density was evaluated in a longitudinal 2-year follow-up, randomized, unblinded, uncontrolled clinical trial conducted in healthy, normally menstruating perimenopausal women, perimenopausal oligomenorrhoic women and in perimenopausal oligomenorrhoic women treated with an oral contraceptive containing 20 microg ethinyl estradiol plus 0.15 mg desogestrel, 0.100 mg levonorgestrel, 0.75 mg of gestodene (n=15 in each group). The results were analyzed by factorial or repeated measures analysis of variance, as appropriate. RESULTS: During the observation period, in normal menstruating women there were no changes in menstrual cycle, plasma FSH and estradiol levels, and spine bone density. In oligomenorrhoic untreated women an increase in cycle length, with a concomitant decrease in plasma estradiol and an increase in plasma FSH levels were evidenced (p<0.05). In this group a significant decrease in bone density (p<0.05) occurred. In OC-treated women, a significant (p<0.05) increase in bone density was observed, with no differences among different groups. CONCLUSION: Different progestins used in OC preparations do not modify the bone sparing effect of perimenopausal OC administration avoiding the decrease in bone density.

Different effect of hormone replacement therapy, DHEAS and tibolone on endothelial function in postmenopausal women with increased cardiovascular risk.

Menopause is associated with an increased cardiovascular risk and with a decrease in endothelial function. Hormone replacement therapy (HRT) improves endothelial function in post-menopausal women (PMW) without established atherosclerosis. New alternative treatments, among which tibolone (T) and DHEAS have been suggested to reduce postmenopausal cardiovascular risk. Although, in vitro animal studies have suggested that T and DHEAS improve endothelial function, their effect in humans has never been tested. The aim of the present study was to compare the effects of HRT (continuous combined 0.625 mg conjugated equine estrogen plus 2.5 mg/d medoxyprogesterone) DHEAS and T on endothelium-dependent flow-mediated vasodilatation (FMD), plasma nitrite, nitrate and endothelin-1 levels in 16 PMW with increased cardiovascular risk in a double-blinded, double-crossover study. Women were randomized and treated for 4 weeks with HRT, T or DHEAS. Brachial artery diameter, FMD, endothelin-1 and plasma nitrite and nitrate levels were measured at baseline and after each treatment phase. Brachial artery diameters remained unchanged after each treatment phase. HRT significantly improved FMD compared to both baseline and to T and DHEAS therapies while no effect of T or DHEAS on FMD was noted. In conclusion, HRT, but neither T nor DHEAS, improves endothelial function and reduces plasma levels of endothelin-1 in PMW at risk of CAD.

Effects of low-dose, continuous combined hormone replacement therapy on sleep in symptomatic postmenopausal women.

Sleep disturbances in peri- and postmenopausal women may result from hormonal changes, vasomotor symptoms, and possibly psychological factors. Hormone replacement therapy (HRT) seems to diminish the disruption of sleep in climacteric women. The aim of this study was to determine the effects of a low dose of conjugated equine estrogens (CE) in combination with different progestins (LD-HRT) and evaluate differences between regimens on sleep in symptomatic postmenopausal women. Postmenopausal women were recruited and assigned to calcium-vitamin (control group) or to LD-HRT with 0.3mg of CE associated with a daily administration at bedtime of a progestin (2.5 mg MPA, CE + MPA, n = 20), or 100 mg natural micronized progesterone (CE + P, n = 20). Subjective symptoms were evaluated by the Greene climacteric scale, and by a visuanalogic graduated scale (0-10) at baseline and after 4, 8, and 12 weeks of study. Greene's scores for the control group were similar to those in LD-HRT group at baseline, and showed no significant modification at all subsequent measurements. Conversely, in LD-HRT group, a significant (P < 0.05) reduction in the scores of all Greene's domains was evident versus corresponding baseline and control group values. Conversely, in LD-HRT group, a significant (P < 0.05) reduction in the scores of all Greene's domains was evident with no difference in the scores of the two treated group. Both CE + MPA and CE + P significantly (P = 0.05) reduced the HF and sleep visuanalogic score in comparison to the control group. The score of sleep was significantly (P = 0.05) lower in the CE + P group in comparison to that measured in the CE + MPA group. No significant correlation between sleep and vasomotor score was found. In conclusion, low estrogen dose may have a value in the treatment of menopausal women in which sleep disturbances may be a symptom of estrogen deprivation. Low-dose estrogen associated with low-dose micronized progesterone may especially benefit women who complain of disturbed sleep.

Effects of oral contraceptives on bone mineral density.

Osteoporosis is a major health problem that leads to a high incidence of spine, radial, and hip fractures. It is now well recognized that a chronically hypoestrogenic state increases bone turnover that, in turn, causes a critical decrease in bone mineral density (BMD), an important determinant of fracture risk. During the premenopausal period, hypogonadism can have deleterious effects on skeletal health by reducing peak bone mass or inducing precocious bone loss. In young women, hypothalamic amenorrhea, caused by gonadotropin-releasing hormone pulsatility dysregulation, is often associated with bone loss. Although the relationship between hypothalamic amenorrhea and bone density is not completely understood, the most plausible intervention for this disorder at the moment seems to be the use of hormone replacement. Oral contraceptives are associated with an improvement in BMD if assumed upon the onset of anovulatory cycles and, therefore, estrogen deficiency, but confer no benefit in healthy women with normal ovarian function. In perimenopausal oligomenorrheic women, the use of oral contraceptives seems to have bone-sparing effects. In conclusion, the protective role of oral contraceptives on bone density is biologically plausible, since this treatment represents a replacement therapy with continuous exposure to exogenous estrogens.

Terapia de Reemplazo Hormonal y riesgo de cancer de mama / Hormone replacement therapy and breast cancer

En los últimos 50 años el segmento más viejo de la población ha crecido más rápidamente que los grupos de edad más jóvenes y la expectativa de vida esta progresivamente en aumento. La perimenopausia representa un tiempo importante para establecer metas de prevención en salud. La terapia de reemplazo hormonal (TRH) puede prevenir los efectos a corto y a largo plazo de la privación de estrógenos. Sin embargo, entre el 80 por ciento y el 95 por ciento de las mujeres en los países occidentales no utilizan la terapia hormonal y el efecto de la TRH en la incidencia de cáncer de mama todavía está en debate. La investigación en estrógenos está descubriendo nuevos conceptos acerca del efecto de estos esferoides en diferentes tejidos blancos. Esas investigaciones están clarificando los beneficios de los estrógenos. La relación entre la administración de esferoides sexuales y el aumento del riesgo de cáncer de mama es plausible, pero hay a lo sumo sólo una modesta asociación entre el uso de TRH y el riesgo de cáncer de mama. Se discute la acción molecular y local de los esferoides ováricos en el tejido mamario

Postmenopausal femur bone loss: effects of a low dose hormone replacement therapy.

OBJECTIVES: Previous studies indicate that low-dose hormone replacement therapy (LD-HRT) can relieve vasomotor symptoms and prevent spine bone loss. METHODS: In the present study, we evaluated the effects of a low dose of conjugated equine estrogens (CEE; 0.3 mg) associated with different progestins in continuous combined scheme [2.5 mg of medroxyprogesterone acetate (n=25), 5 mg dydrogesterone (n=27), 2.5 mg nomegestrol (n=11)] as single group, on femur bone mineral density (BMD) and bone metabolism in young postmenopausal women (

Effects of low-dose, continuous combined estradiol and noretisterone acetate on menopausal quality of life in early postmenopausal women.

OBJECTIVES: To describe the effects of low dose hormonal replacement therapy (LD-HRT) on quality of life in early postmenopausal women, since the postmenopausal estrogen deprivation in mid age women often brings along a series of changes and symptoms, which may greatly affect quality of life. METHODS: Fifty normal postmenopausal women were recruited and randomly treated with LD-HRT, 17beta-estradiol (1 mg/day) and norethisterone acetate (0.5 mg/day) (LD-HRT) or calcium supplement (controls). No significant differences in age, age at menopause, the presence of chronic diseases and socio-economic status were present in the two groups. The Women's Health Questionnaire (WHQ), a validated quality-of-life instrument for perimenopausal and postmenopausal women, was administered at baseline and after 6 and 12 weeks of treatment in both groups. RESULTS: At baseline no significant differences in WHQ scores were present in the two groups. In the control group the scores in all different areas showed no significant modification either after 6 and 12 weeks of observation. Conversely, the LD-HRT group showed a significant decrease in the scores of vasomotor symptoms, somatic symptoms, anxiety/fear, depressed mood and sleep problem items. No effects on memory/concentration and menstrual symptoms areas were evident. CONCLUSION: Although quality of life is also and may be mainly influenced by socio-economic and cultural factors, LD-HRT definitively can improve not only vasomotor symptoms, but also more general aspects of physical and psychological well-being of symptomatic postmenopausal women.