Menstrual disturbance and hypersecretion of progesterone in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

OBJECTIVE

While menstrual disturbance is often quoted as a feature of congenital adrenal hyperplasia (CAH), little is known about the mechanism of this symptom. We set out to determine the relationship between menstrual pattern and biochemical characteristics of women with CAH due to 21-hydroxylase deficiency.

PATIENTS AND DESIGN

All 21 female patients with classic CAH attending the adult endocrinology clinics at The Middlesex Hospital were reviewed. Their ages at menarche and menstrual pattern were recorded and blood samples were taken in the follicular phase of the menstrual cycle when on their usual maintenance therapy.

MEASUREMENTS

Measurements of serum LH, FSH, progesterone, 17 alpha-hydroxyprogesterone, testosterone, androstenedione and plasma renin activity were recorded. Urinary steroid profiles were obtained by gas chromatography and mass spectrometry. Molecular genetic analysis of the 21-hydroxylase gene was performed on leucocyte DNA.

RESULTS

In the 18 patients who had spontaneous menarche the degree of menstrual disturbance and progesterone excess was related to the effectiveness of adrenal suppressive therapy. Three out of 21 patients, however, failed to experience menarche on standard medical therapy. These patients with primary amenorrhoea were characterized by reduced endometrial thickening, by non-suppressible serum progesterone concentrations despite suppression of 17 alpha-hydroxyprogesterone levels and by the presence of progesterone metabolites in urinary steroid profiles. Molecular genetic analysis did not differentiate between patients with raised progesterone concentrations and those without.

CONCLUSION

A subgroup of women with congenital adrenal hyperplasia have the triad of non-suppressible serum progesterone of adrenal origin, primary amenorrhoea and infertility due to failure of endometrial thickening. The characteristic urinary steroid profile best distinguishes this subgroup of women from others with congenital adrenal hyperplasia and menstrual disturbance due to inadequate adrenal suppression.