Caterina Benussi

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.

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.

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.

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.

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, Wards 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.

Risk Identification of Osteoporosis in Postmenopausal Women by a Simple Algorithm Based on Ultrasound Densitometry and Body Mass Index

Dual-energy X-ray absorptiometry (DXA) method is the main device for diagnosing osteoporosis; this method, however, involves the use of expensive equipment. Ultrasound method, being portable, noninvasive, and cost-effective, seems to be an appropriate screening device to identify subjects at risk of osteoporosis. Two hundred and twenty-four postmenopausal women (mean age: 57.9+/-6.2yr) were recruited at 2 Menopause Centers. All subjects were assessed by phalangeal Quantitative Ultrasound (QUS) and by DXA at femur and rachis. Applying the first-level screening strategy, the following risk factors were considered: (1) Amplitude Dependent Speed-of-Sound T-score<-1.8 standard deviation (SD) or Ultrasound Bone Profile Index T-score<-1.8SD; (2) body mass index (BMI)<20kg/m(2). BMI identified 25 subjects (11%) of the total population as at risk, the QUS parameters 100 subjects (45%), and the combination of the 2 showed 118 subjects (53%). The percentage of osteoporotics identified by BMI was 17%, by QUS 78%, and by the combination of the two 90%. The sensitivity of this algorithm was 90%; 53% of the subjects would undergo a further densitometric evaluation, the remaining 47% were correctly identified as not at risk. The diagnostic work up proposed appears effective to be indicated for extensive clinical employment, thanks also to its simplicity.

Perimenopausal Changes in Body Weight, Body Fat Distribution and Hormonal Replacement Therapy

Regional fat distribution differs between men and women, and it is well known to occur both in obese and normal subjects. The typical male fat depot is localized in the abdominal regions, while women show a typical femoral and gluteal fat distribution. Increased body weight, and particularly the central distribution of body fat, is recognized as an independent predictor of cardiovascular disease in women [1–4]. Circulating sex steroids can influence body fat distribution [4], and a trend to a progressive increase in body weight is often observed throughout the climacteric period. However, it remains to be determined if those changes are related to the menopause and estrogen deficiency, to other endocrine modifications, to the aging process, or to all these factors. The issue of body weight has a great importance regarding the acceptance and the compliance to the postmenopausal hormonal replacement therapy (HRT). In fact, HRT has been commonly thought to determine an increase in body weight. This concern represents one of the greatest obstacles for the acceptance and use of long-term HRT, which can not only alleviate subjective symptoms, but also prevent osteoporosis and reduce the risk of cardiovascular disease [5–12]. The aim of the present study was to evaluate the pattern of body weight and body fat distribution in early postmenopausal women and the effects of HRT with an oral estrogen/progestin combination.