Nolvadex, also known as Tamoxifen, is a selective estrogen receptor modulator similar to clomiphene. Many steroid users will use tamoxifen to block the effect of estrogen at the estrogen receptors. Tamoxifen has also been shown to increase the levels of SHBG in the blood1. This is generally considered to be a bad thing by steroid users because it is believed that high SHBG will reduce the effectiveness of a stack by reducing circulating AAS levels. In reality, strong androgens cause a decrease in SHBG levels that can result in higher circulating free estradiol and estrone levels in addition to free androgens which can contribute to the formation of gynecomastia. Additionally, many AAS have little binding to SHBG and circulate largely in the free-state or bound to albumin. It may therefore be advantageous to increase SHBG levels to help sequester circulating estrogens. As stated in the side effects section under gynecomastia, SHBG has been shown to have a protective role against estrogen induced proliferation in the breast2,3,4,5,6,7. Though there is little evidence showing tamoxifen to be effective in preventing gynecomastia, there is considerable evidence that tamoxifen can be used to shrink breast tissue, particularly when it is of the lump variety as opposed to the fatty type8,9,10,11. More so than with clomiphene, the problem with tamoxifen is that most people think that more is better and use too high of a dose. Doses as low as 10 mg per day have been shown to be effective for the treatment of gynecomastia while some will use five or ten times this amount11.
Higher doses of tamoxifen may result in stimulation of estrogen receptors producing the opposite effect to what is desired especially when endogenous estrogen levels have been driven to very low levels with aromatase inhbiitors12. Tamoxifen has been shown in the literature to have similar effects to clomiphene for increasing LH and testosterone levels13. While most aromatase inhibitors have been shown to decrease HDL levels, tamoxifen has been shown in some cases to increase it.
1. Derman O, Kanbur NO, Tokur TE: The effect of tamoxifen on sex hormone binding globulin in adolescents with pubertal gynecomastia. J Pediatr Endocrinol Metab. Aug;17(8):1115-9, 2004
2. Fortunati N, Raineri M, Cignetti A, Hammond GL, Frairia R. Control of the membrane sex hormone-binding globulin-receptor (SHBG-R) in MCF-7 cells: effect of locally produced SHBG. Steroids. 63(5-6):282-4, 1998
3. Fazzari A, Catalano MG, Comba A, Becchis M, Raineri M, Frairia R, Fortunati N. The control of progesterone receptor expression in MCF-7 breast cancer cells: effects of estradiol and sex hormone-binding globulin (SHBG). Mol Cell Endocrinol. 172(1-2):31-6, 2001
4. Försti A, Jin Q, Grzybowska E, Söderberg M, Zientek H, Sieminska M, etal. Sex hormone-binding globulin polymorphisms in familial and sporadic breast cancer. Carcinogenesis. 23(8):1315-20, 2002
5. Catalano MG, Comba A, Fazzari A, Benedusi-Pagliano E, Sberveglieri M, Revelli A, et al. Sex steroid binding protein receptor (SBP-R) is related to a reduced proliferation rate in human breast cancer. Breast Cancer Res Treat. 42(3):227-34, 1997
6. Fissore F, Fortunati N, Comba A, Fazzari A, Gaidano G, Berta L, Frairia R. The receptor-mediated action of sex steroid binding protein (SBP, SHBG): accumulation of cAMP in MCF-7 cells under SBP and estradiol treatment. Steroids. 59(11):661-7, 1994
7. Fortunati N, Fissore F, Fazzari A, Berta L, Benedusi-Pagliano E, Frairia R. Biological relevance of the interaction between sex steroid binding protein and its specific receptor of MCF-7 cells: effect on the estradiol-induced cell proliferation. J Steroid Biochem Mol Biol. 45(5):435-44, 1993
8. Khan HN, Rampaul R, Blamey RW: Management of physiological gynaecomastia with tamoxifen. Breast. Feb;13(1):61-5, 2004
9. Lawrence SE, Faught KA, Vethamuthu J, Lawson ML: Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomastia. J Pediatr. Jul;145(1):71-6, 2004
10. Parte P, Balasinor N, Gill-Sharma MK, Maitra A, Juneja HS: Temporal effect of tamoxifen on cytochrome P450 side chain cleavage gene expression and steroid concentration in adult male rats. J Steroid Biochem Mol Biol. Nov;82(4-5):349-58, 2002
11. Hanavadi S, Banerjee D, Monypenny IJ, Mansel RE. The role of tamoxifen in the management of gynaecomastia. Breast. 15(2):276-80, 2006
12. MacNab MW, Tallarida RJ, Joseph R. An evaluation of tamoxifen as a partial agonist by classical receptor theory–an explanation of the dual action of tamoxifen. Eur J Pharmacol. 103(3-4):321-6, 1984
13. Vandekerckhove P, Lilford R, Vail A, Hughes E: Clomiphene or tamoxifen for idiopathic oligo/asthenospermia. Cochrane Database Syst Rev. (2):CD000151, 2000