Testosterone, SHBG and cardiovascular health in postmenopausal women

Abstract

Cardiovascular disease (CVD) affects men and women differently with women having a lower incidence and later onset of disease. Research has recently refocused interest on the cardiovascular role of androgens. The purpose of this review is to summarize the evidence available on the association between testosterone and cardiovascular health in postmenopausal women. Published studies relating testosterone and sex hormone-binding globulin (SHBG) to CVD and its risk factors were reviewed. Studies included in this review suggest that increased androgenicity, characterized by high testosterone and low SHBG levels, is associated with an adverse CVD risk factor profile in postmenopausal women. However, evidence for an association with cardiovascular events is lacking and it is uncertain whether the observed associations with endogenous testosterone have clinical implications regarding the use of postmenopausal testosterone therapy. Large-scale, longitudinal studies relating testosterone and SHBG levels to cardiovascular risk factors and endpoints are needed to determine the temporal relationship between androgenicity and cardiovascular risk and to ascertain the long-term efficacy and safety of testosterone therapy in postmenopausal women.

Hormonal effects on blood vessels

“…Some studies have reported that high testosterone is associated with an adverse CVD risk factor profile in postmenopausal women, irrespective of polycystic ovary syndrome. 3,124 Polymorphism of the (CAG)n repeat of the AR gene was associated with CVD and risk factor profiles in postmenopausal women. 125 Thus far, evidence is lacking for an association of testosterone with CVD events in women, and it is uncertain whether testosterone could be used as a postmenopausal hormone therapy.…”

Cardiovascular disease among diabetic women with bilateral oophorectomy.

“…Menopause is the transitional period after which the ovaries stop producing eggs, and there is a cessation of menstruation. During this period the levels of both estrogens and androgens are lower than in premenopausal women due to follicular depletion and age-related atrophy of the adrenal cortex (35).…”

“…However, the postmenopausal ovaries remain hormonally active, secreting significant amounts of androgens (35). In women with bilateral salpingo-oophorectomy (BSO), which is the surgical removal of the ovaries, the levels of androgens are lower than in women with natural menopause (36,37).…”

“…While both circulating estrogens (mainly estradiol) and androgens levels fall with menopause due to ovarian follicular depletion and age-related atrophy of the adrenal cortex, there is a drastic reduction in estradiol compared to testosterone, resulting in a more androgenic milieu in older women (35). A reduction in SHBG levels during menopause also fosters this excess androgenic state (233).…”

“…In premenopausal women, 25% of testosterone is derived from the ovaries (35). Another 25% is produced by the adrenal cortex through the stimulation of adrenocorticotropic hormone (ACTH), and 50% is from peripheral conversion of androstenedione, DHEA and DHEA-S (35).…”