Massimo Ciaponi

Prospective evaluation of body weight and body fat distribution in early postmenopausal women with and without hormonal replacement therapy

AIMS In order to assess the effects of menopause and hormonal replacement therapy (HRT) on body weight and body fat distribution (determined by dual energy X-ray), early postmenopausal women were given either oral calcium (500 mg/day, control group, n=13) or HRT, a combination of estradiol valerate (EV, 2 mg/day for 21 days) with cyproterone acetate (CPA, 1 mg/day in the last 10 days of the treatment cycle, n=18; Climen, Schering). RESULTS There were no differences in basal body weight and body fat distribution in the two groups before the study. In control group, a significant (P<0.05) increase in body weight (from 63.5+/-2.0 to 68.7+/-2.0 kg after 36 months) paralleled a shift to a prevalent central, android fat distribution with a slight but significant (P<0.05) increase in total body fat mass (from 23.4+/-2.1 to 29.1+/-2.1 kg), an increase in trunk (from 10.1+/-0.4 to 12.7+/-0.4 kg, P<0.05), arms (from 2.4+/-0.2 to 2.9+/-0.2 kg, P<0.05) and legs (from 6.5+/-0.4 to 7.8+/-0.4 kg, P<0.05) fat. In the HRT group total body bone mineral showed a significant increase (from 1086+/-21 to 1128+/-19 mg/cm(2), P<0.05) increase after 36 months, with no significant increase in body weight (from 62.6+/-1.8 to 65.0+/-1.9 kg), and no modifications in trunk (from 10.0+/-0.2 to 10.1+/-0.2 kg) and arms (from 2.4+/-0.1 to 2.6+/-0.1 kg) fat, but a significant increase in legs fat (from 6.9+/-0.3 to 9.9+/-0.4 kg, P<0.05). CONCLUSION Present results demonstrate that menopause is associated with an accelerated increase in body weight and body fat, with a prevalent central, android fat distribution, that can be counteracted at least in part by oral HRT.

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 Womens 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.

Effects of combined low dose of the isoflavone derivative ipriflavone and estrogen replacement on bone mineral density and metabolism in postmenopausal women

OBJECTIVES To assess the pattern of biochemical markers of bone metabolism and vertebral bone mineral density in early postmenopausal women treated with combined ipriflavone and low dose conjugated estrogens. METHODS Bone biochemical markers and vertebral bone density were evaluated in a longitudinal, comparative, 2 year study conducted in postmenopausal women treated with sole calcium supplementation (500 mg/day), or with either ipriflavone (IP) at the standard dose (600 mg/day) plus the same calcium dose, low dose conjugated estrogens (CE) (0.3 mg/day) plus calcium, or low dose IP (400 mg/day) plus low dose CE (0.3 mg/day) plus calcium. The results were analyzed by repeated measures analysis of variance, as appropriate. RESULTS No modifications of both urinary excretion of hydroxyproline and plasma osteocalcin levels were observed in calcium and in CE-treated women, while vertebral bone density significantly decreased (P < 0.0001) in both groups. In IP or IP + CE-treated women, plasma osteocalcin did not show any modification, while urinary hydroxyproline showed a significant (P < 0.05) decrease, that paralleled a significant (P < 0.05) increase in vertebral bone density. CONCLUSION Postmenopausal IP administration, at the standard dose of 600 mg/day, can prevent the increase in bone turnover and the decrease in bone density that follow ovarian failure. The same effect can be obtained with the combined administration of low dose (400 mg/day) IP with low dose (0.3 mg/day) CE.

Longitudinal Evaluation of Perimenopausal Femoral Bone Loss: Effects of a Low-Dose Oral Contraceptive Preparation on Bone Mineral Density and Metabolism

Abstract: To characterize the pattern of biochemical markers of bone metabolism and femoral bone mineral density in eumenorrheic and oligomenorrheic perimenopausal women, and assess the effects of a low-dose oral contraceptive (OC) on bone metabolism and femoral bone density, bone biochemical markers and femoral bone density (measured at the neck, Ward’s triangle and trochanter regions) were evaluated in a longitudinal 2-year follow-up study. The study was conducted in healthy, normally menstruating perimenopausal women (n= 18), perimenopausal oligomenorrheic women (n= 18), and perimenopausal oligomenorrheic women treated with an OC containing 20 mg ethinylestradiol plus 0.15 mg desogestrel (n= 19). The results were analyzed by factorial or repeated measures analysis of variance, as appropriate. During the observation period, in normally menstruating women there were no changes in the menstrual cycle, plasma FSH and estradiol levels, biochemical markers of bone turnover or femoral bone density. In oligomenorrheic untreated women an increase in cycle length with a concomitant decrease in plasma estradiol and an increase in plasma FSH levels were found (p < 0.05). In this group a significant increase in urinary excretion of hydroxyproline and in plasma osteocalcin levels with a concomitant significant decrease in femoral bone density (p < 0.05) occurred. In OC-treated women, osteocalcin plasma levels and urinary excretion of hydroxyproline significantly (p < 0.05) decreased, leading to a significant (p < 0.05) increase in femoral bone density. It is concluded that perimenopausal OC administration can avoid the increase in bone turnover and the decrease in femoral bone density due to the perimenopausal impairment of ovarian function.

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 (<or=56 years). All women were supplemented with 1 g of calcium per day, and compared with women treated with 1 g of calcium per day alone (control group, n=15). There were no significant differences in age, body mass index (BMI), hormone values, bone metabolism markers and femur BMD in the treatment and control groups before the study. RESULTS In calcium-treated women serum plasma osteocalcin (BGP) and hydroxyproline/creatinine urinary excretion (OHP/Cr) remained stable during all the observation period. In this group, femoral neck, Wards triangle and trochanter BMD showed a progressive and significant (P<0.05) decrease. In the LD-HRT group, a significant (P<0.05) decrease in serum BGP and OHP/Cr was observed. In these women, the values of these markers of bone turnover at 36 months were significantly (P<0.01) different from those of calcium-treated women. During the LD-HRT administration, all BMD measures did not show any significant modifications. In these women, treated with LD-HRT the BMD values were significantly (P<0.05) different from those measured in calcium-treated women in all the femur sites of measurements. In the control group, BMI significantly (P<0.05) increased from baseline value with a weight gain of 3%, while in the LD-HRT group, BMI did not change after 36 months of treatment and the 1.3% gain in body weight was not significant. LD-HRT was effective in reducing menopausal clinical symptoms and provided a favorable bleeding profile, and minimal side effects. CONCLUSION LD-HRT was effective in reducing menopausal clinical symptoms and minimal and transient side effects were reported. In addition, the 0.30 mg/day of CEE, in addition to a proper calcium supplementation, irrespective of the progestin used, can provide effective protection against activation of bone turnover and femur osteopenia.

Postmenopausal osteoporosis management.

Osteoporosis is perhaps the widest-ranging social, physical, and economic impact of estrogen deficiency. Postmenopausal bone loss is the major determinant of osteoporosis. Osteoporotic risk can be determined by measuring bone mineral density using dual X-ray absorptiometry. The radiation free quantitative bone ultrasound is emerging in the assessment of bone structure giving reliable estimates of fracture risk. Diet and exercise are important in determining a womans risks for osteoporosis. Hormone replacement therapy clearly decreases bone turnover and prevents postmenopausal bone loss and reduces fractures. Tibolone as well as raloxifene prevent bone loss and solid data demonstrate a reduction of vertebral fractures after raloxifene administration.

Treatment of postmenopausal vertebral osteopenia with monofluorophospate: A long-term calcium-controlled study

The aim of the present study was to assess the effects of the new fluorine pro-drug monofluorophos-phate (MFP) in postmenopausal women with vertebral osteopenia and high bone turnover. We enrolled postmenopausal women (PMW, 43–59 years) who had had a natural menopause 2–5 years before the study, had vertebral bone mineral density (BMD) <13 SD from the premenopausal mean, and had at least one of the biochemical markers of bone remodeling >1 SD over the mean for premenopausal women. Patients were randomly divided into two treatment groups (group 1, 500 mg/day of oral calcium; group 2, MFP at the dose of 20 mg F-equivalents + 600 mg calcium/day) for 2 years (n=21 in each group). The lumbar vertebral (L2–4) BMD and total body bone mineral (TBBM) were measured by dual-energy X-ray absorptiometry (Lunar DPX, Lunar Corporation, USA). Urinary hydroxyproline excretion (OH-P/Cr), plasma bone Gla protein (BGP) and serum alkaline phosphatase (AP) were assayed. In group 1 the markers of bone turnover and vertebral BMD did not show any significant modification, while TBBM showed a significant (p<0.05) decrease after 24 months. In group 2 a significant (p<0.05) decrease in OH-P/Cr (−23.9±2.0%), and an increase in both BGP (+19.4±2.6%) and AP(+10.3±2.6%) levels were observed after 24 months of MFP administration. In this group, both vertebral BMD (+5.01±0.9%,p<0.01) and TBBM (+4.0±0.6%,p<0.05) showed a significant increase after 24 months. Present results suggest that, in osteopenic PMW, MFP administration induces a significant increase in vertebral BMD without impairment of cortical bone, with a reduction in bone resorption and an increase in bone formation rate.

Bone density changes in postmenopausal women with the administration of ipriflavone alone or in association with low-dose ERT

Ipriflavone is a synthetic flavonoid that has been shown to exert a direct inhibitory effect on osteoclastic activity and possibly stimulate the osteoblast activity in different experimental models. The aim of the present study was to evaluate the effects of either ipriflavone alone or ipriflavone plus low dose hormone replacement therapy (HRT) in the prevention of postmenopausal bone loss. Patients were randomly allocated to different treatment groups receiving calcium (500 mg/day, control group), continuous HRT (25 or 50 micrograms/day of transdermal 17 beta-estradiol) plus medrogestone 5 mg/day for 12 days/month, ipriflavone at the standard dose of 600 mg/day, or finally ipriflavone 600 mg/day plus 17 beta-estradiol 25 micrograms/day plus medrogestone 5 mg/day for 12 days/month. No significant differences in basal levels of biochemical markers of bone turnover or in basal bone mineral density (BMD) values were evident in the different groups. In the control group after 12 months, spine BMD showed a significant (p < 0.05) 3.41% decrease. The pattern of BMD modification was significantly different from controls in the high dose HRT group (+1.84%), the ipriflavone group (+0.11%), and the combined ipriflavone/HRT group (-0.22%). Conversely, the BMD pattern in the low dose HRT group (-0.55%) was similar to that observed in controls. Thus, present results confirm that ipriflavone and 50 micrograms/day of transdermal 17 beta-estradiol are effective measures in the prevention of postmenopausal osteopenia. A lower transdermal estrogen dose is unable to increase the antiresorptive effect of ipriflavone and did not exert any further action in the prevention of postmenopausal osteopenia.

The HRT misuse and osteoporosis epidemic: a possible future scenario

Recent controversies with hormone replacement therapy (HRT) have caused much concern in women and their health-care providers. As a result, the number of HRT users in the USA has fallen dramatically. Consequently, the potential HRT-induced reduction in fracture risk is lost so that, in the next few years, we can expect an excess of 43 008 fractures per year in women aged 65 – 69 years. In addition, the recent evidence on the merits of early initiation of HRT on cardiovascular disease risk and neurocognitive function and the effect of type and combination of hormones on breast cancer risk now require an urgent review by the regulatory authorities of their recommendations about HRT.

Hormone replacement therapy in perimenopause: effect of a low dose oral contraceptive preparation on bone quantitative ultrasound characteristics.

OBJECTIVES Our aim was to assess the effects of a combined oral contraceptive (OC) preparation on bone quantitative ultrasound and biochemical markers of bone metabolism in perimenopausal women. DESIGN Bone biochemical markers and bone quantitative ultrasound were evaluated in a longitudinal 2-year follow-up study conducted in healthy, normally menstruating perimenopausal women, perimenopausal oligomenorrheic women, and age-matched oral contraceptive-treated women (20 micrograms of ethinyl estradiol plus 0.15 mg desogestrel). The results were analyzed by factorial or repeated-measures analysis of variance, as appropriate. RESULTS In normal women, there were no significant modifications in menstrual cycle, plasma FSH and estradiol levels, biochemical markers of bone turnover, and bone quantitative ultrasound. Conversely, in oligomenorrheic women, an increase in the cycle length with a concomitant rise in circulating plasma FSH and parallel decrease of plasma estradiol levels was evident. In this group, an increase in both urinary excretion of hydroxyproline and plasma osteocalcin levels paralleled a decrease in bone quantitative ultrasound. In perimenopausal OC-treated women, the pattern of osteocalcin and urinary excretion of hydroxyproline showed a slight decrease, whereas bone quantitative ultrasound did not show any significant modification. CONCLUSION Perimenopausal OC administration can prevent the increase in bone turnover and the decrease in bone quantitative ultrasound that follow the perimenopausal impairment of ovarian function.