When women are prescribed oral estrogen products, many will eventually experience weight gain. These patients either choose to live with the weight gain, seeing the problem as inevitable, or they discontinue therapy, hoping for relief. Studies show approximately 10 million women in the U.S. use birth control pills and at least an equal number of menopausal women seek hormone replacement relief.
Orally absorbed estrogens enter the body via portal circulation and effect liver-activation of a variety of physiologic pathways. One outcome is increased secretion of binding globulins. When women use oral estrogen therapy, Sex Hormone Binding Globulin has been shown to elevate disproportionately compared to women on transdermal estrogen therapy.1,2,3,4,5
Given that weight gain is a multi-factorial issue, Sex Hormone Binding Globulin can be viewed as a marker worth observing. If SHBG is rising in an estrogen therapy patient, suspect a simultaneous rise in Thyroxine Binding Globulin (TBG). TBG is a high-affinity globulin that only binds thyroid hormones in circulation. It is one of three proteins (along with transthyretin and serum albumin) responsible for transporting the thyroid hormones thyroxine (T4) and triiodothyronine (T3) in the bloodstream. As levels of TBG elevate, less bio-available thyroid hormone will be available for receptor binding sites.
Thyroid hormones (and more specifically bio-available Free-T3) play a significant role in a host of physiologic functions, including overall metabolic rate, body temperature regulation, brain function, oxygen consumption, and cholesterol/lipid levels. Obviously, slowed metabolism and weight gain could be a consequence of an elevating TBG level. Direct lab testing of TBG levels is available and can be used for validation of clinical suspicions.
With judicious monitoring of estrogen therapy for Sex Hormone Binding Globulin levels, the clinician can include or rule out the possible metabolic implications of TBG elevations.
1 Tahboub R, Arafah BM 2009 Sex steroids and the thyroid.; Best Pract Res Clin Endocrinol Metab 23:769-780
2 Chetkowski RJ, et al, J Clin Endocrin Metab 2000;85:4462-4469
3 Crook D, Br J Obstet Gynecol 1997;104 Suppl 16:4-13
4 Nachtigall LE, et al, Menopause 2000;7:243-250
5 Vekhavaara S, et al, Circulation 2000;102;2687