Soy research and expert insights
Sexual Function Normal in Men Consuming Soy
Although consumption of soy isoflavones has been shown to exert beneficial effects on bone, brain, prostate and cardiovascular health1, concerns have been raised that consumption of these dietary estrogens might cause abnormalities in sexual differentiation and feminization in males exposed in utero or during infancy, and might lower testosterone levels and semen quality, adversely affecting fertility in adult men. However, studies investigating hormonal effects of soy consumption by men suggest no effects on sexual function.
These concerns arise mainly from studies in rodents consuming or injected with extremely large quantities of isoflavones during development, although the results of these studies are actually quite variable. For example, perinatal exposure to high doses of purified genistein disrupted sexual differentiation in rats2, 3, and neonatal exposure altered the pituitary response to gonadotropin-releasing hormone (GnRH)4 and induced structural changes similar to those caused by diethylstilbestrol (DES), a potent estrogen.5 However, other rodent studies have shown no effects of genistein on the pituitary response to GnRH6, 7, sperm count7, or gonad histopathology8 and one study reported that soy might actually improve spermatogenesis.9 Badger and colleagues reported that male rats fed soy protein isolate did not differ from rats fed whey protein or casein in development, organ weights, in vitro testosterone metabolism, or reproductive performance at short-term, long-term, or multigenerational endpoints.10 Although no studies have been performed in human infants consuming soy, a follow up study of 120 men who had consumed soy formula as infants also showed no effects on pubertal maturation, fertility or hormonal disorders.11
There is great interspecies variability in effects of isoflavone consumption on reproductive capacity in adult animals. For example, while research on cheetahs12 has demonstrated reproductive toxicity, consumption of up to 9 mg soy isoflavones/kg body weight /day in primates13, 14 and up to 3.5mg/kg body weight /day in pigs15 is not associated with reproductive disturbances. Studies in adult male rodents treated with soy or genistein have found reduced5, 16, unchanged7, 8, 17, and increased18 serum testosterone concentrations.
Two cross-sectional studies evaluating the associations between soy intake and plasma hormones in adult men report conflicting results. Nagata and colleagues19 reported a weak but statistically significant inverse correlation between soyfood consumption and serum estradiol (r = -.32, P = 0.009) and borderline inverse correlations with serum estrone, testosterone and free testosterone in 69 Japanese men. In the second study, with a much larger sample size, Allen and colleagues found no significant associations between consuming dietary soymilk and sex hormone levels in 696 British men.20
Two intervention studies in men consuming soyfoods or supplements containing very high levels (119-120 mg) of isoflavones/- day suggest modest effects on plasma hormones and no effects on semen quality. Habito and colleagues21 performed a randomized crossover study of 42 men who consumed tofu containing 119 mg isoflavones daily for four weeks. Blood concentrations of estradiol, testosterone, dihydrotestosterone (DHT), and androstanediol glucuronide did not differ between the two diets. The mean testosteroneestradiol ratio was 10 percent lower, sex hormone binding globulin (SHBG) was 9 percent higher, and the free androgen index (total testosterone/SHBG x 100) was 7 percent lower after tofu consumption, suggesting a slight lowering of androgen activity. These data are consistent with those of Gardner- Thorpe and colleagues22, who reported a 6 percent lowering of testosterone, and no significant changes in DHT, estradiol, estrone or SHBG in men consuming soy flour containing 120 mg isoflavones/day for six weeks. However, the relevance of these last results22 is questionable because control data were not reported.
This slight reduction in androgen activity was not confirmed by two studies using isoflavone doses nearer to the typical intake of regular soy consumers.23 Nagata and colleagues24 conducted a parallelarm study of 34 men, half of whom consumed an average of 343 mL soymilk (48 mg isoflavones) daily for two months. Blood concentrations of estradiol, total and free testosterone, and SHBG did not differ between the two groups, although estrone concentrations tended to decrease in the group consuming soymilk. These results are consistent with those of Mitchell and colleagues25, who found no changes in serum concentrations of estradiol, testosterone, follicle-stimulating hormone, or luteinizing hormone in 14 young men consuming a tablet containing 40 mg/day of soy isoflavones for two months. In this same study, no effects were seen on testicular or ejaculate volume or sperm concentration, count or motility.
In summary, although animal studies suggest a theoretical risk of reproductive problems in men exposed to soy isoflavones during development or as adults, it is clear that these effects are quite variable among animal species and are observed only at extremely high doses. Studies investigating hormonal effects of soy or isoflavone consumption in men suggest small reductions in androgen activity and no effects on fertility. The slight reduction in androgen activity observed in two studies of men consuming high quantities of isoflavones are unlikely to be of clinical significance, particularly in light of the lack of effects on sperm quality and fertility reported in other studies. On the basis of the available data, there is little reason to think that soy consumption will cause reproductive abnormalities or feminization in men.
ABOUT THE AUTHORS
Jill Hamilton-Reeves is a graduate student pursuing her doctoral degree in nutrition at the University of Minnesota. She is currently investigating the effects of soy phytoestrogen consumption on reproductive hormones and prostate tissue markers of cell proliferation and androgren activity in men at high risk of prostate cancer. Mindy S. Kurzer, Ph.D., teaches and performs research in human nutrition in the Department of Food Science and Nutrition at the University of Minnesota. Her current research focuses on the biological effects of phytoestrogen consumption.
1) Gooren LJ, Toorians AW. Significance of oestrogens in male (patho)physiology. Ann Endocrinol 2003; 64(2): 126-135.
2) Levy JR, Faber KA, Ayyash L, Hughes CL Jr. The effect of prenatal exposure to the phytoestrogen genistein on sexual differentiation in rats. Proc Soc Exp Biol Med. 1995; 208(1): 60-6.
3) Wisniewski AB, Klein SL, Lakshmanan Y, Gearhart JP. Exposure to genistein during gestation and lactation demasculinizes the reproductive system in rats. J Urol. 2003; 169(4): 1582-6.
4) Faber KA, Hughes CL. The effect of neonatal exposure to diethylstilbestrol, genistein, and zearalenone on pituitary responsiveness and sexually dimorphic nucleus volume in the castrated adult rat. Biol Reprod 1991; 45:649-653.
5) Strauss L, Makela S, Joshi S, Huhtaniemi I, Santti R. Genistein exerts estrogen-like effects in male mouse reproductive tract. Mol Cell Endocrinol 1998; 144:83-93.
6) Lewis RW, Brooks N, Milburn GM, Soames A, Stone S, Hall M, and Ashby J. The effects of the phytoestrogen genistein on the postnatal development of the rat. Toxicol Sci 2003; 71: 74-83.
7) Roberts D, Veeramachaneni DN, Schlaff WD, Awoniyi CA. Effects of chronic dietary exposure to genistein, a phytoestrogen, during various stages of development on reproductive hormones and spermatogenesis in rats. Endocrine J 2000; 13:281-286.
8) Nagao T, Yoshimura S, Saito Y, Nakagomi M, Usumi K, Ono H. Reproductive effects in male and female rats of neonatal exposure to genistein. Reprod Toxicol 2001; 15:399-411.
9) Robertson KM, O'Donnell L, Simpson ER, Jones ME. The phenotype of the aromatase knockout mouse reveals dietary phytoestrogens impact significantly on testis function. Endocrinol 2002; 143(8): 2913-21.
10) Badger TM, Ronis MJ, Hakkak R. Developmental effects and health aspects of soy protein isolate, casein, and whey in male and female rats. Int J Toxicol 2001; 10(3): 165-74.
11) Strom BL, Schinnar R, Ziegler EE, Barnhart KT, Sammel MD, Macones GA, Stallings VA, Drulis JM, Nelson SE, Hanson SA. Exposure to soybased formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA 2001; 286(7): 807-14.
12) Setchell KD, Gosselin SJ, Welsh MB, Johnston JO, Balistreri WF, Kramer LW, Dresser BL, Tarr MJ. Dietary estrogens--a probable cause of infertility and liver disease in captive cheetahs. Gastroenterology 1987; 93(2): 225-33.
13) Anthony MS, Clarkson TB, Hughes CL Jr, Morgan TM, Burke GL. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys. J Nutr 1996; 126:43-50.
14) Harrison RM, Phillippi PP, Swan KF, Henson MC. Effect of genistein on steroid hormone production in the pregnant rhesus monkey. Exp Biol Med 1999; 222:78-84.
15) National Research Council, Subcommittee on Swine Nutrition, Committee on Animal Nutrition Board on Agriculture. Nutrient requirements of swine, 10th revised ed. Washington, DC: National Academy Press, 1988.
16) Weber KS, Setchell KD, Stocco DM, Lephart ED. Dietary soy-phytoe-strogens decrease testosterone levels and prostate weight without altering LH, prostate 5 alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague-Dawley rats. J Endocrinol 2001; 170(3): 591-9.
17) Kwon SM, Kim SI, Chun DC, Cho NH, Chung BC, Park BW, Hong SJ. Development of rat prostatitis model by oral administration of isoflavone and its characteristics. Yonsei Med J 2001; 42(4): 395-404.
18) Dalu A, Laydes B, Bryant C, Latendresse J, Weis C and Delclos K. Estrogen receptor expression in the prostate of rats treated with dietary genistein. J Chromatogr B 2002; 777 (1- 2): 249-260.
19) Nagata C, Inaba S, Kawakami, Kakizoe T, Shimizu H. Inverse association of soy product intake with serum androgen and estrogen concentrations in Japanese men. Nutr Cancer 2000; 36:14-18. 20) Allen NE, Appleby PN, Davey GK, Key TJ. Soy milk intake in relation to serum sex hormone levels in British men. Nutr Cancer 2001; 41: 41-6.
21) Habito RC, Montalto J, Leslie E, Ball MJ. Effects of replacing meat with soyabean in the diet on sex hormone concentrations in healthy adult males. Br J Nutr 2000; 84:557-563.
22) Gardner-Thorpe D, O’Hagen C, Young I, Lewis SJ. Dietary supplements of soya flour lower serum testosterone concentrations and improve markers of oxidative stress in men. Eur J Clin Nutr 2003; 57:100-6.
23) Coward L. Barnes NC, Setchell KDR, Barnes S. The isoflavones genistein and daidzein in soyabean foods from American and Asian diets. J Agric Food Chem 1993; 41:1961-7.
24) Nagata C, Takatsuka N, Shimizu H, Hayashi H, Akamatsu T, Murase K. Effect of soymilk consumption on serum estrogen and androgen concentrations in Japanese men. Cancer Epidemiol Biomarkers Prev 2001; 10:179-184.
25) Mitchell JH, Cawood E, Kinniburgh D, Provan A, Collins AR, Irvine DS. Effect of a phytoestrogen food supplement on reproductive health in normal males. Clin Sci 2001; 100:613-618.