Reply to Phytoestrogens: The Pediatric Perspective
To the Editor:
The issue that Dr. Couper raised about a possible association between exposure to phytoestrogens in male children and decreased sperm count later in life was first suggested in Lancet in 1993 (1) but has not been confirmed in animal or human studies. Indeed, cows and ewes fed estrogenic forage showed transiently impaired ovarian function, but males were relatively unaffected (2). More specifically, gestational and lactational exposure to isoflavones had no adverse effects on gametogenetic function or reproductive organs in male rats (3,4), nor did they alter the reproductive hormone concentrations and reproductive organ weights in peripubertal rhesus monkeys of both sexes (5). In a recent retrospective cohort study among adults who, as infants, participated in a feeding study with soy- or cow-milk formulas, no adverse reproductive effects were identified in association with previous exposure to soy formula (6). In another pioneering study, isoflavone supplements to the diet of healthy adult volunteers for a period of 2 months had no observable effects on testicular volume or semen parameters of ejaculate volume: sperm concentration or total count, motility, and morphology (7). The deleterious effect of phytoestrogens on male fertility is unfounded based on the current data.
The second concern about the casual relationship between phytoestrogens and early onset of menarche also is unfounded. We have reviewed several studies, all of them in rats, that showed either delay (8) or acceleration of puberty (9) in response to phytoestrogens exposure. As we specifically emphasized, there are no similar studies in girls. Therefore, extrapolating the data from rats to humans, and even further, to delineate conclusions about breast cancer risk is definitely unjustified. Indeed some studies have shown that phytoestrogens have protective effects against breast cancer (10).
Finally, others have not confirmed significant aluminium contamination of soy formulae, and this may be a problem specific to Australia.
We are not advocates of phytoestrogens usage in childhood, but we disagree with Dr. Couper's conclusion of avoiding soy formulae if possible.
1. Sharpe Rm, Skakkebaek NE. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet 1993; 341:1392–5.
2. Adams NR. Detection of the effects of phytoestrogens on sheep and cattle. J Anim Sci 1995; 73:1509–15.
3. Awoniyi CA, Roberts D, Chandrashekar V, et al. Neonatal exposure to coumestrol, a phytoestrogen, does not alter spermatogenic potential in rats. Endocrine 1997; 7:337–41.
4. Roberts D, Veeramachaneni DN, Schlaff WD, et al. Effects of chronic dietary exposure to genistein, a phytoestrogen, during various stages of development on reproductive hormones and spermatogenesis in rats. Endocrine 2000; 13:281–6.
5. Anthony MS, Clarkson TB, Hughes Jr, CL et al. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive systems of peripubertal rhesus monkeys. J Nutr 1996; 126:43–50.
6. Strom BL, Schinnar R, Ziegler EE, et al. Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA 2001; 286:807–14.
7. Mitchell JH, Cawood E, Kinniburg D, et al. Effect of a phytoestrogen food supplement on reproductive health in normal males. Clin Sci (Colch) 2001; 100:613–8.
8. Levy JR, Faber KA, Ayyash L, et al. The effect of prenatal exposure to the phytoestrogen genistein on sexual differentiation in rats. Proc Soc Exp Biol Med 1995; 208:60–6.
9. Casanova M, You L, Gaido KW, et al. Developmental effects of dietary phytoestrogens in Sprague-Dawley rats and interactions of genistein and daidzein with rat estrogen receptor alpha and beta in vitro. Toxicol Sci 1999; 51:236–44.
10. Ingram D, Sanders K, Kolybaba M, et al. Case-control study of phyto-estrogens and breast cancer. Lancet 1997; 350:990–4.