Clinical and metabolic effects of drospirenone-estradiol in menopausal women: a prospective study.

OBJECTIVES: To describe the effects of low-dose hormonal replacement therapy (HRT) on quality of life, metabolic parameters and blood pressure in postmenopausal women. METHODS: Postmenopausal women untreated with HRT or sex steroids in the previous 12 months were randomized to treatment with 17ß-estradiol (1 mg/day) plus drospirenone (2 mg/day) (E2+DRSP) or to calcium (controls). Quality of life was evaluated by the Women's Health Questionnaire (WHQ) at baseline and after 6 and 12 weeks of treatment. Anthropometric, metabolic and blood pressure measurements were performed before and after 3 months of treatment. RESULTS: WHQ domain scores for vasomotor and somatic symptoms, anxiety/fears, depressed mood, sexual behavior and sleep problems decreased significantly in the E2+DRSP group relative to both baseline and control values (p < 0.05). Body mass index was unchanged, while waist circumference decreased significantly (p < 0.001) after E2+DRSP treatment. Significant decreases were also observed after E2+DRSP treatment for blood insulin values, insulin resistance (estimated by homeostasis model assessment) and systolic blood pressure (p < 0.001, all). In subjects with systolic blood pressure < 130 mmHg at baseline, no changes in systolic values were registered, while women with baseline high-normal systolic blood pressure (130-139 mmHg) showed significant decreases (p < 0.0069). E2+DRSP did not modify diastolic blood pressure values. In the calcium-treatment group, there were no significant changes in WHQ scores or in anthropometric, metabolic or blood pressure measurements. CONCLUSION: In postmenopausal women, E2+DRSP administration improves vasomotor symptoms and general aspects of quality of life and may positively influence cardiovascular risk factors.

The relative contributions of menopause and aging to postmenopausal reduction in intervertebral disk height.

AIM: To evaluate, in a population of normal women, the effects of aging and menopause on the height of intervertebral discs by measuring the intervertebral disk space, between the 12th thoracic and 4th lumbar vertebrae, by dual-energy X-ray absorptiometry (DXA). MATERIALS AND METHODS: The study was conducted on 2455 consecutive women attending our Department, from whom 464 normal women were selected. The measurement was validated utilizing a spine phantom. RESULTS: The phantom mean intervertebral disk space was 0.44 cm, with a coefficient of variation of 1.4%. The coefficients of variation in premenopausal, early postmenopausal and elderly women were 2.2, 2.0 and 6.0%, respectively. Values of intervertebral disk space were stable from age 20 to 50 years, thereafter showing a significant (p < 0.05) decrease, negatively correlated with both age and years since menopause (p < 0.0001). In postmenopausal women younger than 60 years, a correlation (p = 0.042) was evident between intervertebral disk space and years since menopause, but no correlation was evident with age. In women over 60 years, no correlations were found between intervertebral disk space and either age or years since menopause. In three groups of age-matched women (47.5 +/- 1.5 years, n = 39 in each group), intervertebral disk space was significantly (p < 0.0001) lower in postmenopausal than in both premenopausal and perimenopausal women. CONCLUSION: The DXA measurement of intervertebral disk space is precise. After menopause, intervertebral disk space shows a progressive decrease that almost entirely occurs in the first 5 - 10 years since menopause, suggesting that the estrogen decrease may rapidly change connective tissue metabolism in the intervertebral disks.

A longitudinal evaluation of the effect of two doses of tibolone on bone density and metabolism in early postmenopausal women.

Tibolone, a steroid with tissue-specific activities, can reduce the bone resorption that takes place after the menopause. The present calcium-controlled, 2-year study aimed to evaluate the effect of two doses of oral tibolone, 1.25 mg and 2.5 mg, on bone loss in early postmenopausal women. The subjects were randomly allocated to one of the three groups, namely tibolone 2.5 mg (n = 30), tibolone 1.25 mg (n = 30) and a control group (n = 30). All subjects received 1000 mg of calcium per day. In the control group, vertebral and femur bone mineral density (BMD) decreased significantly (p < 0.05) after 12 and 24 months. In both tibolone groups, vertebral and femur BMD increased significantly (p < 0.05) increased after 12 and 24 months. In the control group, bone turnover markers (urinary excretion of hydroxyproline/creatinine and plasma osteocalcin levels) remained constant, while in both tibolone groups these markers showed similar significant decreases (p < 0.05) after 12 and 24 months. After 24 months, body weight increased in the control group (p < 0.05), while smaller increments were evident in the tibolone groups. Symptom scores in the control group did not show any significant modification during the study. In contrast, the administration of 2.5 mg tibolone was significantly (p < 0.05) effective in reducing hot flushes and other symptoms. The tibolone 1.25 mg group yielded similar results (even if it was proportionally less efficient) to the higher dose. It is concluded that tibolone is effective, even at lower doses, in relieving climacteric symptoms and preventing a decrease in spine and femur BMD in early postmenopausal women.

[Aerodiol: the efficacy and tolerability of intranasal estrogen administration. An overview]. / Aerodiol: efficacia e tollerabilità degli estrogeni somministrati per via nasale. Compendio.

UNLABELLED: Estrogen supplementation, given mainly by oral or transdermal route has been shown to decrease climacteric symptoms, bone turnover, prevent postmenopausal bone loss, and significantly reduce fracture risk in both early and late postmenopausal women. Estrogens exert their principal biological effects through the actions on 2 different intracellular estrogen receptor (ER) proteins, ERa and ERb. These receptors, are completely distinct in their action. However, regardless the type of receptor involved, the response induced through the action of ER induction can be dependent also on the total dose exposure rather than estradiol concentrations at subsaturating levels. The nasal route is an effective and well-established route of drug delivery. Nasal administration produces a pulsed profile of plasma estradiol, with plasma levels rising rapidly and returning to pre-administration levels within 12 h (fall to 10% of their peak level within approximately 2 h). As a consequence, daily intranasal administration results in a pulse-like estrogen profile, rather than the relatively sustained serum levels attained with both oral and transdermal administration. In addition, exposure obtained with a single dose is compared with the exposure obtained with the same total dose given as 2 divided doses administered 12 h apart. It's known that different route of administration exert different biological and clinical RESULTS: In the years, several clinical studies have demonstrated the efficacy and safety of intranasal estradiol in the treatment of climacteric symptoms, compared with other routes of estrogen administration. Interestingly, intranasal therapy also showed a lower tendency to stimulate endometrial proliferation than the oral route, with a high incidence of atrophic endometrium maintained during the long-term study. The reduced level of stimulation of the reproductive organs produced by Aerodiol compared with oral estradiol therapy of equivalent efficacy on climacteric symptoms may be related to the pulsed kinetic profile of estradiol exposure that occurs with the intranasal route. Improvement of climacteric symptoms observed with nasal estradiol administration is comparable to that seen with transdermal or oral estrogens. A similar reduction in Kupperman Index or in the number of hot flushes was reported over a 6-month period with results similar to those of several studies performed with transdermal patches delivering estradiol or with conjugated equine estrogen. Different routes of administration may exert different results in terms of compliance, biological and clinical effects even if long term clinical trials are needed for demonstrating it. The pulsed kinetics of Aerodiol may exert less side effects in terms of coagulation cascade activation and a favourable lipid profile with less mammary tissue stimulation. These aspects became of paramount importance since the recent publication of 2 trials, Women Health Initiative (WHI) and Heart and Estrogen/Progestin Replacement Study (HERS), regardless their important population selection bias and uncertain results, left important consequences in terms of HRT indication and use for both women and clinicians. In conclusion, Aerodiol introduces the new concept of pulsed estrogen therapy. Pulsed estrogen therapy is safe, well accepted and highly efficient in alleviating postmenopausal symptoms and prevent postmenopausal bone loss. Aerodiol therapy demonstrated also a lower stimulation of reproductive tissues (endometrium, breast) compared with the equivalent oral therapy, with important repercussion for future HRT strategies.

Effects of low-dose continuous combined conjugated estrogens and medroxyprogesterone acetate on menopausal symptoms, body weight, bone density, and metabolism in postmenopausal women.

OBJECTIVE: The purpose of this study was to determine the effects of a low dose of conjugated equine estrogens and medroxyprogesterone acetate plus calcium supplementation on bone density, metabolism, body weight, and symptoms in young postmenopausal women. STUDY DESIGN: Sixty postmenopausal women, aged 45 to 56 years, were randomized in an open-label, 2-year trial that compared treatment with low-dose continuous combined hormone replacement therapy that contained 0.3 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate plus 1000 mg of calcium per day or treatment with 1000 mg of calcium per day alone. Menopausal symptoms were evaluated for the first 12 weeks of the study; bleeding profiles, bone mineral density, bone turnover, and body weight were assessed for 24 months. RESULTS: After 24 months, we evaluated 15 subjects in the control group (with a 50% drop-out rate) and 23 patients (with a 23% drop-out rate) in the low-dose continuous combined hormone replacement therapy group. Low-dose continuous combined hormone replacement therapy was effective in reducing menopausal clinical symptoms and provided a favorable bleeding profile and minimal side effects. In comparison with basal values, bone mineral density significantly (P <.05) increased by 2.72% +/- 0.3% in the low-dose continuous combined hormone replacement therapy group and decreased by 7.9% +/- 0.8% (P <.05) in the control group after 24 months, with parallel changes in bone metabolism marker action. In the control group, body mass index significantly (P <.05) increased from baseline value with a weight gain of 3%; in the low-dose continuous combined hormone replacement therapy group, the body mass index did not change after 24 months of treatment, and the 1.3% gain in body weight was not significant. CONCLUSION: Low-dose continuous combined hormone replacement therapy can alleviate subjective symptoms and minimize body transformations that are associated with early menopause and provide an effective protection against the activation of bone turnover and osteoporosis.

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.

Longitudinal evaluation of perimenopausal femoral bone loss: effects of a low-dose oral contraceptive preparation on bone mineral density and metabolism.

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 microg 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.

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.

Climacteric modifications in body weight and fat tissue distribution.

OBJECTIVE: To estimate the effects of climacteric modifications on body weight and fat distribution. METHODS: From 8764 women attending the authors' Menopause Clinic, 1075 untreated, normal healthy women were selected and divided into three groups: premenopausal (n = 380), perimenopausal (n = 263) and postmenopausal (n = 432). The total body fat tissue mass and distribution were analyzed using the dual energy X-ray method. RESULTS: Body weight and body mass index (BMI) were significantly higher in perimenopausal and postmenopausal than in premenopausal women. The mean total body fat and the percentage of fat with respect to soft tissue were significantly (p < 0.05) higher in the perimenopausal and postmenopausal groups than in the premenopausal group. The amount of fat tissue and the regional fat percentage with respect to total fat tissue were higher in the trunk (p < 0.05) and arm (p < 0.05) regions in perimenopausal and postmenopausal than in premenopausal women. In the postmenopausal group, the leg fat tissue was significantly (p < 0.05) less than in the premenopausal and perimenopausal groups. Total body and leg lean tissue was significantly (p < 0.01) less in postmenopausal than in premenopausal and perimenopausal women. In the premenopausal group, body weight and BMI were positively correlated with age (r = 0.37 and r = 0.54, respectively). No significant correlations were observed in the perimenopausal group. In postmenopausal women, body weight and BMI were loosely correlated with age (r = 0.13 and r = 0.11, respectively). In three groups of 63 age-matched women, with similar BMI, the percentage of total body fat with respect to soft tissue was significantly (p < 0.001) higher in the perimenopausal and postmenopausal groups than in the premenopausal group. Regarding body fat distribution, the percentage of fat with respect to total fat tissue was significantly higher in the trunk (p < 0.001) region in perimenopausal and postmenopausal women than in premenopausal women. In the leg region, the percentage of fat with respect to total fat tissue was significantly (p < 0.05) higher in the premenopausal group than in the postmenopausal group. In the arm region, a slight but not significant (p < 0.08) difference was shown in fat distribution among the three groups. CONCLUSIONS: Climacteric changes rather than the aging process are relevant for prediction of body weight and fat distribution, especially for perimenopausal and postmenopausal women, who show a shift to a central, android fat distribution.

Quantitative bone ultrasonometry in climacteric women.

Quantitative bone ultrasound (QUS) measurement is an emerging technique in the assessment of osteoporosis risk. In this study, bone mineral density (BMD) (mg/cm2) of lumbar vertebrae, neck, Ward's triangle and trochanter were measured by DXA and the phalanx amplitude dependent speed of sound (AD-SOS) was measured by QUS in climacteric (n = 1025) women. The relationship between AD-SOS and BMD values at different skeletal sites was significant, even if the analysis showed poor correlation coefficients. These data seem to indicate that QUS can detect bone characteristics in addition to density. The AD-SOS was higher in premenopausal than in perimenopausal women. The AD-SOS further decreases in postmenopausal women without hormone replacement. The age at menopause is relevant for predicting the AD-SOS in the postmenopausal years. Conversely, the maintenance of a regular menstrual function is associated with higher AD-SOS. Thus, the early impairment and cessation of ovarian function can lead to an earlier and/or sharper decline in bone homeostasis that can be detected by QUS. In conclusion, AD-SOS is a valuable index in detecting menopausal bone loss, and could be used for the patient follow-up during menopausal transition and in therapeutic trials.

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.

Body weight, body fat distribution, and hormonal replacement therapy in early postmenopausal women.

Body weight was measured, and body fat distribution was determined by dual energy x-ray in early postmenopausal women given either oral calcium (500 mg/day; control group; n = 12) or hormonal replacement therapy (HRT), a combination of estradiol valerate (2 mg/day for 21 days) with cyproterone acetate (1 mg/day in the last 10 days of the treatment cycle; n = 15). There were no differences in basal body weight or body fat distribution in the two groups before the study. In the control group, a significant (P < 0.05) increase in body weight (from 63.6 +/- 2.2 to 65.2 +/- 1.9 kg [corrected] after 12 months) paralleled a slight, but significant (P < 0.05), increase in total body fat mass (from 23.8 +/- 2.2 to 24.7 +/- 2.2 kg), with an increase in fat in the trunk (from 10.2 +/- 0.4 to 11.3 +/- 0.4 kg; P < 0.01) and arms (from 2.4 +/- 0.5 to 2.7 +/- 0.2 kg; P < 0.05). These findings demonstrate a shift to a prevalent central android fat distribution after 12 months of observation in untreated postmenopausal women. Conversely, in the HRT group, total body bone mineral showed a significant (from 1089 +/- 28 to 1106 +/- 29 mg/cm2; P < 0.05) increase after 12 months, with no significant increase in body weight (from 62.2 +/- 1.6 to 62.7 +/- 1.6 kg), and no modifications in trunk (from 10.0 +/- 0.2 to 9.8 +/- 0.3 kg) and arm (from 2.43 +/- 0.2 to 2.5 +/- 0.1 kg) fat, but a significant increase in leg fat (from 7.1 +/- 0.3 to 8.3 +/- 0.4 kg; P < 0.05). The present results suggest that HRT can counteract at least in part the postmenopausal increase in body weight and body fat and prevent central body fat distribution after menopause.

Ipriflavone prevents the loss of bone mass in pharmacological menopause induced by GnRH-agonists.

In a double-blind, placebo controlled study, ipriflavone (600 mg/day, T.D.D.) or identical placebo tablets were given with 500 mg/day of calcium to patients treated with the gonadotropin hormone-releasing hormone agonist (Gn-RH-A) leuproreline acetate, 3.75 mg every 30 days for 6 months. In placebo-treated subjects (n = 39), urinary hydroxyproline excretion and plasma osteocalcin levels showed a significant (P < 0.01 and P < 0.05, respectively) increase, whereas spine bone density and total body bone density significantly (P < 0.001 and P < 0.05, respectively) decreased after 3 and 6 months of GnRH-A administration. Conversely, in the ipriflavone-treated group (n = 39), no significant difference in bone markers and bone density was evidenced. These data indicate that ipriflavone can restrain the bone remodeling processes and prevent the rapid bone loss that follows medically induced hypogonadism.

Ultrasonographic bone characteristics during normal pregnancy: longitudinal and cross-sectional evaluation.

OBJECTIVE: We evaluated the pattern of bone density during pregnancy by radiation-free ultrasonographic densitometry. STUDY DESIGN: In a longitudinal study we measured bone mineral density in a group of 10 normal primiparous women, from the fourteenth to the thirty-eighth weeks of pregnancy. In a cross-sectional study bone mineral density was determined in a group of 85 normal primiparous women, in different weeks of pregnancy. RESULTS: In the longitudinal study ultrasonographic bone density was stable in the first part of pregnancy, whereas a significant (p < 0.05) decrease was evidenced during the third trimester. A negative correlation between bone density and weeks of pregnancy (p < 0.0001) was evidenced in the cross-sectional study. CONCLUSION: During physiologic pregnancy the calcium mobilization from the maternal bone stores to accomplish the fetal needs can cause a significant decrease in maternal bone density in the last trimester of gestation.

Effects of a new estrogen/progestin combination in the treatment of postmenopausal syndrome.

Postmenopausal women were randomly given either oral calcium (500 mg/day, control group, n = 12) or 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 = 19). EV+CPA reduced (P < 0.01) postmenopausal complaints, inducing regular withdrawal bleeds, with no hysteroscopic or hystologic evidence of endometrial hyperstimulation after 12 months of treatment. In the control group, spine bone mineral density (BMD) and the total body bone mineral (TBBM) decreased (P < 0.01), whereas urinary hydroxyproline excretion (OH-P/Cr), plasma bone Gla Protein (BGP) and lipid profile did not show any significant modification throughout the study. In the EV+CPA group, urinary OHP/Cr and plasma BGP levels decreased (P < 0.01) after 6 and 12 months, whereas both BMD and TBBM showed a small but significant (P < 0.01) increase. In this group, LDL cholesterol significantly (P < 0.01) decreased and HDL levels significantly (P < 0.01) increased after 6 and 12 months. In conclusion, the EV+CPA combination is effective in relieving menopausal symptoms, produces a good cycle control and a favourable lipid profile, preventing postmenopausal bone resorption.

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 monofluorophosphate (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) < 1 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.

Hormone replacement therapy in perimenopausal women with a low dose oral contraceptive preparation: effects on bone mineral density and metabolism.

In a 2-year longitudinal, calcium-controlled study we evaluated bone density and metabolism in perimenopausal women with initial ovarian failure, and the effects of hormone replacement with a low dose oral contraceptive preparation (OC). In perimenopausal oligomenorrhoic women (n = 16) a significant (P < 0.01) increase in cycle length and plasma FSH levels as well as a parallel decrease in plasma estradiol levels (P < 0.01) were evident. In this group, despite the calcium supplementation (500 mg/day), a significant (P < 0.001) increase in the biochemical markers of bone remodelling paralleled a significant (P < 0.001) decrease (-3.4% after 24 months) in bone density. Conversely, in premenopausal oligomenorrhoic women treated with a low dose oral contraceptive (OC) formulation (30 mcg ethinyl estradiol plus 75 mcg gestodene, n = 16), bone markers showed a significant (P < 0.01) decrease, that paralleled a slight but significant (P < 0.01) increase (+1.71%) in bone density. These data suggest that premenopausal administration of OC can prevent the acceleration of bone turnover and reverse the decrease in bone density that follows the premenopausal impairment of ovarian function.

Ipriflavone prevents the bone mass reduction in premenopausal women treated with gonadotropin hormone-releasing hormone agonists.

In the present study we assessed the effects of ipriflavone in the prevention of increased bone turnover and the rapid bone loss that follows medical induced hypogonadism caused by the administration of a gonadotropin hormone-releasing hormone agonist (GnRH-A). In a double blind, placebo-controlled study, ipriflavone (600 mg/day, tdd (three divided doses)) or identical placebo tablets were given with 500 mg/day of calcium to patients treated with 3.75 mg leuproreline acetate every 30 days, for 6 months. In placebo-treated subjects (n = 39), urinary hydroxyproline excretion and plasma bone GLA protein levels showed a substantial (P < 0.01) increase, while spine bone density and total body bone density significantly (P < 0.01) decreased after 3 and 6 months of GnRH-A administration. Conversely, in ipriflavone treated group (n = 39), no significant difference in bone markers and bone density was evidenced. These data indicate that ipriflavone can restrain the bone remodeling processes and prevent the rapid bone loss that follows medical induced hypogonadism. Thus, ipriflavone administration can be of value in the prevention of osteopenia in women treated with GnRH-A.

Bone loss in perimenopausal women: a longitudinal study.

A longitudinal evaluation of bone mineral density (BMD) and metabolism was performed in premenopausal women. During the 2-year observation period, the menstrual pattern, plasma estradiol and FSH levels as well as the values of bone markers and BMD did not show any significant modification in a group of eumenorrhoic women (n = 37). Conversely, in age-matched oligomenorrhoic women (n = 37) a significant (P < 0.05) increase in the cycle length with a concomitant significant (P < 0.05) increase in circulating plasma FSH and parallel decrease of plasma estradiol levels (P < 0.05) was evident. In this group a significant (P < 0.05) increase in both urinary excretion of OH-P/Cr and plasma BGP levels paralleled a significant (P < 0.05) decrease in radial BMD. These data suggest that premenopausal impairment of ovarian function can lead to a bone loss in a significant proportion of women in which prevention should be considered before menopause.

Longitudinal evaluation of perimenopausal vertebral bone loss: effects of a low-dose oral contraceptive preparation on bone mineral density and metabolism.

OBJECTIVE: To characterize the pattern of biochemical markers of bone metabolism and vertebral bone mineral density in eumenorrheic and oligomenorrheic perimenopausal women and to assess the effects of a combined oral contraceptive (OC) preparation on bone mass and metabolism. METHODS: Bone biochemical markers and vertebral bone density were evaluated in a longitudinal 2-year follow-up study conducted in healthy, normally menstruating perimenopausal women, perimenopausal oligomenorrheic women, and age-matched oligomenorrheic OC-treated women (20 micrograms ethinyl estradiol [E2] plus 0.15 mg desogestrel) (n = 27 in each group). The results were analyzed by factorial or repeated-measures analysis of variance, as appropriate. RESULTS: During our observation period, there were no significant modifications in menstrual cycle, plasma FSH and E2 levels, biochemical markers of bone turnover, and vertebral bone density in normal women. Conversely, oligomenorrheic women showed an increase in the cycle length with a concomitant decrease of plasma E2 and a corresponding rise in circulating plasma FSH levels (P < .05). In this group, an increase in both urinary excretion of hydroxyproline and plasma osteocalcin levels paralleled a significant decrease in vertebral bone density (P < .0001). In OC-treated women, the pattern of osteocalcin showed no modification, whereas urinary excretion of hydroxyproline showed a decrease, which paralleled a significant (P < .001) increase in vertebral bone density. CONCLUSION: Perimenopausal OC administration can prevent the increase in bone turnover and the decrease in bone density that follow the perimenopausal impairment of ovarian function.