Different effects of tibolone and continuous combined estrogen plus progestogen hormone therapy on sex hormone binding globulin and free testosterone levels – an association with mammographic density

Abstract

Estrogens were markedly increased and androgens decreased by E2/NETA. In contrast, tibolone had only a minor influence on circulating estrogens. Sex hormone binding globulin (SHBG) levels were reduced by 50%, while levels of androgens increased. Baseline values of estrone sulfate (E1S), around 1.0-1.1 nmol/l, were increased to 44.7 nmol/l by E2/NETA and to only 1.7 nmol/l by tibolone (p < 0.001). Mammographic breast density displayed a negative correlation with age and body mass index and a positive association with SHBG. After 6 months there was also a negative correlation with levels of free testosterone. Conclusion We found that tibolone and E2/NETA caused distinct differences in estrogen/androgen status and blood levels of possible breast mitogens. The negative association between free testosterone and mammographic density could be a possible explanation for tibolone having less influence on the breast.

Selective Tissue Distribution of Tibolone Metabolites in Mature Ovariectomized Female Cynomolgus Monkeys after Multiple Doses of Tibolone

“…These observations suggest antiestrogenic effects of tibolone on breast tissue, in line with its neutral effects on mammographic density and its low incidence of breast tenderness in postmenopausal women (Lundström et al, 2002;Hofling et al, 2005).…”

Associations between serum testosterone levels, cell proliferation and progesterone receptor content in normal and malignant breast tissue in postmenopausal women

“…The first study included 149 healthy postmenopausal women participating in a clinical trial of HT [19]. The second study included 48 consecutive postmenopausal women with breast cancer participating in an ongoing clinical trial on endocrine treatment of breast cancer [22]; Table I shows their tumor characteristics.…”

“…epithelium, connective tissue, blood vessels and fat [16,17]. Recent studies have shown that mammographic density seems to be inversely correlated to low levels of both total and free testosterone [18][19][20] and directly correlated with breast cell proliferation [21].…”

“…We have recently published two endocrine-related studies in postmenopausal women, one dealing with mammographic density and endocrine data during different regimens of HT in healthy women [19] and the other with endocrine treatment of breast cancer [22]. Besides endocrine data, data on breast proliferation, expressed as percentage of MIB-1 þ cells, were available for the healthy women and data for PR in breast tumor tissue for the breast cancer patients.…”

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“…Although the effects of tibolone on the breast are not completely clear, evidence so far suggest that it does not increase mammographic density (58,59). Tamoxifen treatment reduces mammographic density, at least in premenopausal women (60,61), and treatment with a hormone regimen that reduces serum levels of estrogen and progesterone also reduces mammographic density (62,63).…”