Fertility in women with late-onset adrenal hyperplasia due to 21-hydroxylase deficiency.

Abstract

Fertility was evaluated in 53 female patients with late-onset adrenal hyperplasia (LAH) due to 21-hydroxylase deficiency. The majority of patients (n = 33) were seen for isolated postpubertal hirsutism, 9 patients consulted for sterility, and 11 for irregular menstrual cycles. At the time of diagnosis, the ages of patients ranged from 15-40 yr (mean +/- SD, 24.6 +/- 5.2). No patient had major signs of virilization. The plasma 17-hydroxyprogesterone level was higher than normal in all patients (26.8 +/- 18.9 nmol/L; range, 3.4-139.4) and dramatically increased to 140.1 +/- 80.6 nmol/L (range, 35.2-324.2) after ACTH treatment. Plasma androgen levels were high (testosterone, 3.25 +/- 2.03 nmol/L; delta 4-androstenedione, 13.65 +/- 5.60 nmol/L). Plasma basal and LHRH-stimulated values were normal for FSH and high for LH. Basal and TRH-stimulated plasma PRL levels were normal. Among these 53 LAH patients, only 20 desired a pregnancy. These had a total of 38 pregnancies. Ten patients became pregnant before the diagnosis of LAH and without any treatment; they had a total of 18 pregnancies, 12 of which were successful. Moreover, 19 normal pregnancies without any spontaneous abortion were carried to term by 14 of 16 hydrocortisone-treated patients. One patient needed the association of one cure of clomiphene citrate. Hypofertility in LAH patients seems, therefore, to be relative. Its mechanism is hormonal, with anovulation or dysovulation, due to the continuous steroid feedback of adrenal origin on the hypothalamo-pituitary axis. Hydrocortisone is the appropriate treatment in most cases, reducing adrenal androgen overproduction and relieving hypothalamic-pituitary gonadotropin function, thereby making possible cyclic ovarian activity and ovulations.

Nonclassic Congenital Adrenal Hyperplasia

“…Many women with NCAH are relatively fertile [57, 58]. However, NCAH carries a greater risk of subfertility, in part due to the prevailing ovulatory dysfunction.…”

Sexual Function and Fertility in Adult Females and Males with Congenital Adrenal Hyperplasia

“…Infertility in females with non-classic 21-OHD, who present with no signs of prenatal virilization, seems to be relative [12]. Though unsubstituted women often present with absent or irregular menses, signs of androgen excess and polycystic ovaries, most of them achieve regular ovulatory menstrual cycles and are able to conceive with adequate supplementation of glucocorticoids.…”

“…Thus the main mechanism for infertility in non-classic 21-OHD is indeed an overproduction of adrenal androgens. In a French study of 53 women with non-classic 21-OHD, 20 women who desired a pregnancy had a total of 38 pregnancies, resulting in 31 full-term live births [12]. Only 1 woman needed treatment other than glucocorticoids to conceive.…”

“…In addition, adrenal androgens may directly inhibit folliculogenesis by a negative effect on aromatase activity in granulosa cells [25]. Adequate suppression of adrenal androgens can restore regular menstrual cycles in nearly all women with non-classic 21-OHD [12], but this is not the case for women with classic 21-OHD [9, 13, 16]. Importantly, androgen excess may cause early miscarriages during the first trimester, as suggested by the high number of spontaneous abortions in women with non-classic 21-OHD unsubstituted with glucocorticoids.…”

“…Importantly, androgen excess may cause early miscarriages during the first trimester, as suggested by the high number of spontaneous abortions in women with non-classic 21-OHD unsubstituted with glucocorticoids. In a French study on women with non-classic 21-OHD, 18 pregnancies in women receiving no glucocorticoid substitution led to 6 first trimester spontaneous abortions [12]. …”