PRENATAL SEX-HORMONES AND THE DEVELOPING BRAIN - EFFECTS ON PSYCHOSEXUAL DIFFERENTIATION AND COGNITIVE FUNCTION

This paper hypothesizes that sex hormones may have an influence on human brain differentiation and thus play a role in psychosexual differentiation. Such effects, if any, would be clinically relevant to the management of patients with a problem of intersexuality and for the evaluation of pregnancy drugs. A review of studies on patients with endocrine syndromes, including those with an excess or lack of androgen during fetal development strongly suggest that prenatal hormones exert a limited effect on sex-dimorphic behaviors such as physical energy expenditure, childhood rehearsal of parenting, and other related behaviors. The effects of hormone administration during pregnancy are not well known because relevant research studies are rare and often have methodological problems due to the necessary long-term follow-up studies and its attendant logistical problems. Available information therefore is fragmentary. With progestogens, extensive animal research has shown both androgenic and antiandrogenic effects of various progestogens on genital differentiation, gonadotropin regulation, and sex-dimorphic behavior. In humans, administration of certain C-19-derived progestogens has resulted in genital masculinization of a significant minority of female newborns. However, studies have also shown that while these exposed girls exhibited long-term tomboyism, their gender identity was feminine. There was also no evidence that such females, after puberty, developed a homosexual orientation. Boys exposed to medroxyprogesterone acetate in 1 study did not differ significantly from normal controls with respect to a variety of sex-dimorphic behaviors. On the other hand, exogenous estrogens, both steroidal and nonsteroidal, have been shown to exert paradoxical effects on genital morphology and behavior in subhuman animals, i.e., masculinize females and demasculinize males. In humans however, no investigations have yet been reported on behavior effects of prenatal estrogen treatment alone in man, and studies on estrogen-progestogen combination in human subjects have yielded inconclusive results regarding sex-dimorphic behavior.