Serum estrogen level after hormone replacement therapy and body mass index in postmenopausal and bilaterally ovariectomized women.

OBJECTIVE: The objective of this study was to determine the relationships of serum estrogen levels after hormone replacement therapy (HRT) every other day and every day with body mass index (BMI) in postmenopausal and bilaterally ovariectomized women. METHODS: Eighty-six postmenopausal and 51 bilaterally ovariectomized women who had been suffering from vasomotor symptoms such as hot flush or atrophy of the vagina were randomly treated with HRT every other day or every day. Seventy-four patients received oral administration of 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) every other day, and 63 patients received oral administration of 0.625 mg CEE and 2.5 mg MPA every day as conventional HRT. RESULTS: Eighty-four postmenopausal and 50 bilaterally ovariectomized women completed this study. Serum estradiol levels after HRT every day in postmenopausal and bilaterally ovariectomized women were significantly (P <0.05 and <0.01, respectively) correlated with BMI, while those after HRT every other day were not correlated with BMI. The differences between estradiol levels after 12 months of treatment and initial estradiol levels were also significantly (P <0.01) correlated with BMI in both postmenopausal and bilaterally ovariectomized women who received HRT every day but not in women who received HRT every other day. Serum estrone level after HRT every day and the difference between estrone level after 12 months of treatment and initial estrone level were significantly (P <0.05 and <0.01, respectively) correlated with BMI only in bilaterally ovariectomized women. CONCLUSION: Serum estradiol levels after HRT every day increase more in overweight women than in non-overweight postmenopausal and bilaterally ovariectomized women. The results of the present study regarding the relationship between serum estradiol levels after HRT and BMI should be useful for selecting dosages of drugs to be used in HRT.

Serum estradiol concentration as measured by HPLC-RIA and bone mineral density in postmenopausal women during hormone replacement therapy.

OBJECTIVE: To determine the relationship between the serum estradiol concentration and bone mineral density (BMD) of the lumbar spine in postmenopausal women treated with conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) every other day and every day. METHODS: Eighty-four postmenopausal women were randomly treated with hormone replacement therapy (HRT) every other day and every day. Forty-seven women received oral administration of 0.625 mg CEE and 2.5 mg MPA every other day, and 37 women received oral administration of 0.625 mg CEE and 2.5 mg MPA every day. BMD of the lumbar spine at 12 months and serum concentrations of estradiol and estrone at 6 and 12 months after treatment were examined. RESULTS: The estradiol concentration in subjects treated every other day showed a significant (p < 0.001) positive correlation with the percentage change in lumbar BMD, while that in subjects treated every day was not correlated with the percentage change in BMD. The differences between serum estradiol concentrations after 12 months of treatment and initial serum estradiol values in women treated every other day and every day also showed a significant (p < 0.01 and 0.05, respectively) positive correlation with percentage changes in BMD. In women treated every other day, body mass index (BMI) in the subjects in whom BMD did not increase was significantly (p < 0.01) lower than that in the subjects in whom BMD did increase. CONCLUSIONS: The serum estradiol concentration in women treated every other day has a strong positive correlation with the percentage change in lumbar BMD, but a higher estradiol concentration may be needed for women in whom BMD did not increase with HRT every other day after due consideration of individual characteristics such as BMI.

Circulating osteoprotegerin in women during GnRH-agonist treatment and their relationships with mineral components and biomarkers of bone turnover.

A novel cytokine termed osteoprotegerin (OPG) that is also called osteoclastogenesis-inhibitory factor, which inhibits osteoclast maturation and activity, was recently isolated. In order to determine the influence of estrogen deficiency on the levels of circulating OPG in women, we studied the changes in the levels of circulating OPG in 10 Japanese women ages 25-49 (mean +/- SD, 34.0 +/- 6.9) years with endometriosis receiving gonadotropin-releasing hormone agonists (GnRH-a) therapy. We further analyzed whether the levels of circulating OPG have relations with the levels of the biomarkers of bone turnover or those of circulating mineral components in these patients during GnRH-a treatment. The patients were treated with a monthly injection of 3.75 mg leuprolide acetate depot for 6 months. In all patients, the concentrations of serum estradiol decreased after 6 months of GnRH-a treatment. The bone mineral density of the lumber spines in these patients significantly (P < 0.01) decreased (percentage change: mean +/- SD, -5.4 +/- 2.1%), while circulating OPG levels significantly (P < 0.01) increased after 6 months of treatment. The values of circulating OPG had significant correlations with those of urinary pyridinoline (r = 0.59, P < 0.01), urinary deoxypylridinoline (Dpd) (r = 0.46, P < 0.05), and serum alkaline phosphatase (r = 0.66, P < 0.01) but not with those of serum carboxy-terminal propeptide of type I procollagen during GnRH-a treatment. The values of circulating OPG also correlated significantly with those of serum calcium (Ca) and phosphorus (P) (r = 0.65 and 0.72, P < 0.01). Further analyses revealed that the percentage change in the value of circulating OPG had a significant correlation with that of urinary Dpd (r = 0.84, P < 0.01). These results suggest that circulating OPG levels rise against the increase in osteoblastic bone resorption and circulating Ca levels in the case of estrogen deficiency, possibly as a compensatory mechanism serving to limit circulating Ca levels and bone density.

The obesity in bilateral ovariectomized rats is related to a decrease in the expression of leptin receptors in the brain.

We investigated the expression levels of leptin receptors in the brain of ovariectomized (OVX) rats. The mean expression level of ob mRNA in adipose tissues of OVX rats was significantly (P < 0.01) lower than that in the SHAM operation group rats, and the mean body weight of OVX rats was significantly (P < 0.01) greater than that in the SHAM group rats. However, there were no differences between serum leptin concentrations in these two groups. The mean level of leptin receptor (OB-R) mRNA expression in the brain tissue and the mean level of long form type OB-R (OB-RL) mRNA expression in the hypothalamus of the OVX rats were significantly (P < 0.05) lower than those in the SHAM group rats. These changes were cancelled by supplementation with 17 beta-estradiol in OVX rats. These results suggested that not only changes in the expression level of ob mRNA in adipose tissue and the serum leptin concentration but also changes in the OB-R mRNA in the brain are involved in the body weight increase in OVX rats and that a decrease in OB-R makes transmission of signals to suppress the amount of food intake difficult, thus leading to an increase in body weight.