Dietary Supplement
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports investigating the potential teratogenic effects from use of dehydroepiandrosterone (DHEA) in human pregnancy have been located. DHEA and its active metabolite (DHEA sulfate; DHEA-S) are weak androgens and intermediates in the biosynthesis of testosterone and estradiol. The animal reproduction data suggest that DHEA and/or DHEA-S may cause virilization of the external genitalia in female fetuses and inhibit implantation or development of the pregnancy when administered shortly after conception. However, the doses used in these studies were not compared with the human dose based on BSA or AUC, so the results might not be interpretable for estimating human risk. Moreover, DHEA-S, and probably also DHEA, crosses the human placenta. Although the intrauterine fluid DHEA-S concentrations were very low, higher levels in the embryos and fetuses may have been present. If the agent is used in pregnancy, the patient should be informed of the animal data and limited human pregnancy experience.
FETAL RISK SUMMARY
Although not approved by the FDA, DHEA is available as an over-the-counter nutritional or dietary supplement. The dose of the drug in individual products is not known. Endogenous DHEA and DHEA-S are secreted by the adrenal cortex. In the systemic circulation, most DHEA is present as DHEA-S. DHEA has been promoted for treatment of systemic lupus erythematosus, fat burn, boosting libido, as an anti-aging treatment, and for other uses, but none of these benefits has been demonstrated in controlled studies. In the plasma, DHEA is weakly bound, whereas DHEA-S is strongly bound to albumin. The half-lives of DHEA and DHEA-S are 1–3 hours and 10–20 hours, respectively (1). The metabolic clearance rate of DHEA-S fluctuates throughout pregnancy (2).
Developmental and reproductive toxicity of DHEA has been studied in three species. In rats, DHEA was associated with failure of implantation (3) and dose-related virilization of female fetuses (increased anogenital distance) and reduced fetal weight (4). Rats exposed to DHEA on gestation days 6–17 demonstrated increased early resorptions (5). In mice, prenatal exposure to DHEA on days 11–17 was associated with increased anogenital distance but did not have a significant effect on behavior of the offspring (6). In another study, maternal weight, number, survival, and weight of pups were affected by DHEA (7). In rabbits, no effects on embryonic or fetal development were seen at various doses of DHEA during gestation days 7–20 (5).
No studies on the carcinogenic or mutagenic potential of DHEA have been located. However, a European case–control study found an association between higher serum concentrations of DHEA-S and breast cancer (8).
DHEA-S, and most likely DHEA, crosses the human placenta. This is consistent with the molecular weights of the two compounds, about 288 and 371, respectively. DHEA-S was found in intrauterine fluids only at the limit of detection in a study of 12 pregnant women at a gestational age of 8–12 weeks (9). The authors postulated that because the concentration of androgens was much lower in the intrauterine fluids compared with maternal serum, that there might be a mechanism for the protection of the embryo from higher concentrations of these hormones. Concentrations in the embryos or fetuses were not measured.
In a study of 25 women with diminished ovarian reserve, patients received 25 mg of DHEA three times daily for 16 weeks between two in vitro fertilization (IVF) cycles (10). Significant increases in fertilized oocytes, normal 3-day embryos, embryos transferred, and average embryo scores per oocyte were observed. A follow-up case–control study with 190 women undergoing IVF treatment due to diminished ovarian function demonstrated that DHEA supplementation resulted in significantly higher cumulative pregnancy rates (11).
BREASTFEEDING SUMMARY
No reports on the use of DHEA during lactation have been located. Estrogens have been associated with decreased milk production and concentrations of nitrogen and protein (see Ethinyl Estradiol). As DHEA is an intermediate in the biosynthesis of estrogen, it could decrease milk production as well (12). Although it has not been studied, this effect should be dose-related. If used during breastfeeding, infant weight gain should be closely monitored.
References
1.Kroboth PD, Salek FS, Pittenger AL, Fabian TJ, Frye RF. DHEA and DHEA-S: a review. J Clin Pharmacol 1999;39:327–48.
2.Cohen H, Cohen M. DHAS half-life in pregnancy, its prognostic value in high risk pregnancies. J Steroid Biochem 1977;8:381–3.
3.Harper MJ. Estrogenic effects of dehydroepiandrosterone and its sulfate in rats. Endocrinology 1969;84:229–35.
4.Goldman AS. Virilization of the external genitalia of the female rat fetus by dehydroepiandrosterone. Endocrinology 1970;87:432–5.
5.Kirchner DL, Mercieca MD, Crowell JA, Levine BS. Developmental toxicity of dehydroepiandrosterone (DHEA) in rats and rabbits. Teratology 1998;57:243.
6.Gandelman R, Simon NG, McDermott NJ. Prenatal exposure to testosterone and its precursors influences morphology and later behavioral responsiveness to testosterone of female mice. Physiol Behav 1979;23:23–6.
7.de Catanzaro D, MacNiven E, Ricciuti F. Comparison of the adverse effects of adrenal and ovarian steroids on early pregnancy in mice. Psychoneuroendocrinology 1991;16:525–36.
8.Kaaks R, Berrino F, Key T, Rinaldi S, Dossus L, Biessy C, Secreto G, Amiano P, Bingham S, Boeing H, Bueno de Mesquita HB, Chang-Claude J, Clavel-Chapelon F, Fournier A, van Gils CH, Gonzalez CA, Gurrea AB, Critselis E, Khaw KT, Krogh V, Lahmann PH, Nagel G, Olsen A, Onland-Moret NC, Overvad K, Palli D, Panico S, Peeters P, Quirós JR, Roddam A, Thiebaut A, Tjønneland A, Chirlaque MD, Trichopoulou A, Trichopoulos D, Tumino R, Vineis P, Norat T, Ferrari P, Slimani N, Riboli E. Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst 2005;97:755–65.
9.Atkinson G, Campbell DJ, Cawood ML, Oakey RE. Steroids in human intrauterine fluids of early pregnancy. Clin Endocrinol (Oxf) 1996;44:435–40.
10.Barad D, Gleicher N. Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod 2006;21:2845–9.
11.Barad D, Brill H, Gleicher N. Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function. J Assist Reprod Genet 2007;24:629–34.
12.Oladapo OT, Fawole B. Treatments for suppression of lactation. Cochrane Database Syst Rev 2009;(1):CD005937.