Sex Steroids and Bone Density in Premenopausal and Perimenopausal Women

Abstract

Bone density begins to decline in women before menopause, and the degree of bone loss is variable. We performed a cross-sectional analysis on the entry data of a 5-yr prospective study of risk factors for osteoporosis to determine the correlation of bone density with serum sex steroid concentrations and body weight. We studied 292 healthy white women, aged 35-50 yr, who were menstruating regularly or had had menses in the past 12 months. Blood samples were drawn in the early follicular phase for estradiol (E2), testosterone (T), dehydroepiandrosterone sulfate, and sex hormone-binding globulin (SHBG). Free levels of E2 (FE2) and T (FT) were calculated based on total T and E2, SHBG, and albumin levels. Women were classified as premenopausal (FSH, less than 12 U/L) and perimenopausal (FSH greater than or equal to 12 U/L; n = 46; 16%). Bone density was measured by dual photon absorptiometry of the lumbar spine (L2-L4) and hip and by single photon absorptiometry of the wrist. Perimenopausal women were older than premenopausal women (45.5 +/- 3.5 and 41.0 +/- 3.9 yr, respectively), but did not differ in height or weight. While bone density did not correlate with age in each group, perimenopausal women had significantly lower bone density at the L2-L4 and femoral neck (L2-L4, 1.18 +/- 0.14 in perimenopausal and 1.24 +/- 0.12 g/cm2 in premenopausal women; femur, 0.84 +/- 0.11 in perimenopausal and 0.90 +/- 0.11 g/cm2 in premenopausal women; P less than 0.005). Body weight showed the strongest positive correlation with bone density. Log FT, percent FT, and FE2 percent correlated positively with bone density, even after controlling for weight. Log SHBG was negatively correlated with bone density in premenopausal women at the hip and wrist after controlling for weight. FSH was inversely correlated with bone density, and E2 and T were lower in perimenopausal than premenopausal women. These data suggest that women who are still menstruating may have relative deficiencies in both E2 and T, with reduced bone densities as a consequence.

Bioavailability and metabolism of oral and percutaneous dehydroepiandrosterone in postmenopausal women

“…In fact, age-related bone loss has been reported to begin in the fourth decade and changes in bone turnover have been found well before menopause [42][43][44]. In agreement with these findings, bone density was lower at all sites examined in women classified as perimenopausal compared to premenopausal [45]. In agreement with these findings, the changes in precursor androgen secretion by the adrenals precede by 10-20 years the decrease in ovarian estrogen secretion which abruptly stops at menopause [28].…”

The effects of hyperprolactinemia on bone and fat

“…The role of progesterone in maintenance of bone mass has not been studied in these subjects but there is a relationship between bone density and serum androgens. In healthy premenopausal women there is a positive correlation between free testosterone and bone density [32], and women with hyperprolactinemic and hypothalamic amenorrhea have lower free testosterone than those with regular menses [13,16]. In a cross sectional study we noted a relationship between testosterone and spinal bone mass in a sub-group of amenorrheic subjects [10].…”

Bones and Crohn's: Problems and solutions

“…Androgen deficiency is associated with osteopenia in both men and women (149)(150)(151)(152)(153), probably because of defective osteoblast activity and reduced bone formation (154). Corticosteroid use has been associated with declines in serum testosterone concentration in males (155,156).…”