LACK OF EFFECT OF OESTROGENS ON ADRENAL ANDROGEN SECRETION IN CHILDREN AND ADOLESCENTS WITH A COMMENT ON OESTROGENS AND PUBIC HAIR GROWTH

To study the effect of oestrogen on adrenarche and adrenal androgen secretion we measured plasma concentrations of dehydroepiandrosterone-sulphate (DHEA-S), androstenedione (Δ⁴A) and oestradiol (E₂) in the following groups: children with premature adrenarche; agonadal patients before and after initiation of oestrogen replacement therapy; and, children exposed to increased concentrations of endogenous oestrogen at a precocious age. Fourteen of fifteen patients with premature adrenarche had plasma E₂ levels in the normal prepubertal range (> 10 pg/ml), despite a mean DHEA-S concentration that was significantly elevated for age (6–8 years: 72·5 ± 12·6 μg/dl v. 11·4 ± 2·9 μg/dl, P 0·002). DHEA-S and Δ⁴ A concentrations in fifteen patients with gonadal dysgenesis before and 2–14 months after initiation of oestrogen replacement therapy were not significantly different despite the appearance of oestrogen-induced secondary sex characteristics. Six of fifteen patients developed increased pubic hair during oestrogen therapy but had no increase in the concentrations of plasma DHEA-S. Two patients (aged 1 year 4 months and 4 years 10 months) with oestradrol secreting ovarian follicular cysts (plasma E₂ 11–796 pg/ml) and one patient (aged 6 years 10 months) who had had a granulosa cell tumour of the ovary maintained preadrenarchal DHEA-S levels (> 6·2 μg/dl) despite exposure to concentrations of circulating oestrogen that were high for their chronological age. We interpret the results as follows: (1) Initiation of premature adrenarche occurs without an increase into the early pubertal range of E₂ levels. (2) Administration of replacement doses of oestrogen does not increase adrenal androgen concentrations in adolescent patients with gonadal dysgenesis. (3) Elevated plasma concentrations of endogenous ovarian oestrogens at a precocious age did not increase adrenal androgen secretion in childhood. Thus, it appears that circulating oestrogens are either required for the activation or maintenance of adrenarche nor do they significantly affect the plasma concentrations of adrenal androgens in children and adolescents. (4) The pubic hair growth associated with the institution of oestrogen replacement in adolescent patients with gonadal dysgenesis is not mediated by an increase in adrenal androgen secretion and may result from a specific effect of oestrogen on androgen action at the target tissue (pubic skin).