Bone Mass in Hirsute Women With Androgen Excess

Dixon, Jill E.; Rodin, A.; Murby, Brian; Chapman, Michael; Fogelman, Ignac

doi:10.1111/j.1365-2265.1989.tb02235.x

Cited by 59 publications

(21 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Estrogen deficiency drives menopausal bone loss and can be used therapeutically to prevent such loss (1,2). Estrogen deficiency also plays a primary role in the bone loss associated with menstrual disturbances in young women (3)(4)(5)(6), although there may be circumstances where the detrimental skeletal effects of estrogen deficiency can be avoided (8)(9)(10)(11). In the healthy, normally cycling women recruited for the current study, after 3-5 yr of follow-up, there was evidence of premenopausal bone loss only from the hip.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and postmenopausal women.

Slemenda¹,

Longcope²,

Hui³

et al. 1996

J. Clin. Invest.

290

147

View full text Add to dashboard Cite

Although bone loss around the time of menopause is driven by estrogen deficiency, the roles of estrogens and androgens in the preservation of skeletal mass at other stages of life are less well understood. To address this issue we studied 231 women between the ages of 32 and 77 with multiple measurements of sex steroids and bone mass over a period of 2-8 yr. In all women bone mass was negatively associated with concentrations of sex-hormone binding globulin, and positively associated with weight. Bone loss occurred from all skeletal sites in peri-and postmenopausal women, but premenopausal women lost bone only from the hip ( Ϫ 0.3% ր yr) and had positive rates of change in the radius and spine. Bone loss was significantly associated with lower androgen concentrations in premenopausal women, and with lower estrogens and androgens in peri-and postmenopausal women. Sex steroids are important for the maintenance of skeletal integrity before menopause, and for as long as 20-25 yr afterwards. ( J. Clin. Invest. 1996. 97:14-21.)

show abstract

Section: Discussionmentioning

confidence: 99%

“…Perimenopausal women with higher testosterone concentrations have slower rates of bone loss than those with lower concentrations, independent of their estrogen status (7). Premenopausal women with androgen excess have higher than normal bone mass with or without (8,11) normal menstrual cycling.…”

Section: Introductionmentioning

confidence: 99%

Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and postmenopausal women.

Slemenda¹,

Longcope²,

Hui³

et al. 1996

J. Clin. Invest.

290

147

View full text Add to dashboard Cite

show abstract

“…Furthermore, the nonaromatizable androgen 5a-dihydrotestosterone has been shown to stimulate bone growth in osteopenic ovariectomized rats (24). In pre-and postmenopausal women, endogenous androgen levels correlate with BMD (25,26). Furthermore, a study comparing estrogen to a synthetic androgen in postmenopausal osteoporotic women showed that both steroids were equally effective in reducing bone resorption (27).…”

Section: Introductionmentioning

confidence: 99%

Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen

Ariazi

Leitão

Oprea

et al. 2007

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Aromatase inhibitors (AI) are being evaluated as longterm adjuvant therapies and chemopreventives in breast cancer. However, there are concerns about bone mineral density loss in an estrogen-free environment. Unlike nonsteroidal AIs, the steroidal AI exemestane may exert beneficial effects on bone through its primary metabolite 17-hydroexemestane. We investigated 17-hydroexemestane and observed it bound estrogen receptor A (ERA) very weakly and androgen receptor (AR) strongly. Next, we evaluated 17-hydroexemestane in MCF-7 and T47D breast cancer cells and attributed dependency of its effects on ER or AR using the antiestrogen fulvestrant or the antiandrogen bicalutamide. 17-Hydroexemestane induced proliferation, stimulated cell cycle progression and regulated transcription at high sub-micromolar and micromolar concentrations through ER in both cell lines, but through AR at low nanomolar concentrations selectively in T47D cells. Responses of each cell type to high and low concentrations of the nonaromatizable synthetic androgen R1881 paralleled those of 17-hydroexemestane. 17-Hydroexemestane downregulated ERA protein levels at high concentrations in a cell type -specific manner similarly as 17B-estradiol, and increased AR protein accumulation at low concentrations in both cell types similarly as R1881. Computer docking indicated that the 17B-OH group of 17-hydroexemestane relative to the 17-keto group of exemestane contributed significantly more intermolecular interaction energy toward binding AR than ERA. Molecular modeling also indicated that 17-hydroexemestane interacted with ERA and AR through selective recognition motifs employed by 17B-estradiol and R1881, respectively. We conclude that 17-hydroexemestane exerts biological effects as an androgen. These results may have important implications for long-term maintenance of patients with AIs.

show abstract

“…Further, testosterone deficiency has been implicated as a causative factor in female osteoporosis with the decline of adrenal androgens associated with aging [Gasperino, 1995;Wild et al, 1987]. Androgens have been shown to maintain normal bone mass despite undetectable levels of estradiol [Dixon et al, 1989], and androgen therapy in postmenopausal women has been shown to prevent bone loss [Need et al, 1989]. Androgen receptors have been identified in the nucleus and cytosol of osteoblasts [Nakano et al, 1994;Orwoll et al, 1991].…”

mentioning

confidence: 99%

Simultaneous detection and functional response of testosterone and estradiol receptors in osteoblast plasma membranes

Armen

2000

J. Cell. Biochem.

View full text Add to dashboard Cite

Osteoblasts derived from the periosteal surfaces of two-three-week-old male broiler chicken tibias were cultured for eight days. The cells were then loaded with fura-2/AM ester to detect surges in intracellular Ca(2+). Treatment with 10(-7) M testosterone (T) or 17beta-estradiol (E) elicited a rapid (within seconds) response that was substantially reduced by introducing the calcium chelating agent EGTA or the calcium-channel blocker verapamil. The hormones were equally effective when covalently linked to bovine serum albumin (BSA), a procedure that ensures the hormone does not enter the cells. The rapid response to surface-bound steroids indicates that the responses were invoked through plasma-membrane receptors. The source of Ca(2+) was shown to be through entry from external sources, as well as from intracellular stores. Flow cytometry of fluorescein-tagged T-BSA and E-BSA revealed that osteoblasts derived from male chickens had similar and substantial levels of both receptors.

show abstract

Bone Mass in Hirsute Women With Androgen Excess

Cited by 59 publications

References 30 publications

Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and postmenopausal women.

Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and postmenopausal women.

Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen

Simultaneous detection and functional response of testosterone and estradiol receptors in osteoblast plasma membranes

Contact Info

Product

Resources

About