Adrenal progesterone, 17α-hydroxyprogesterone and cortisol responses to Synacthen in normal women and women with various gynaecological disorders

In apparently normal subjects there is marked heterogeneity in the adrenal's capacity to produce the progestogens progesterone (Po) and 17α-hydroxyprogesterone (17Po). We have now screened for the possibility that adrenal progestogens might be an aetiological factor in some patients with hitherto unexplained gynaecological disorders by measuring the responses to acute stimulation with ACTH after overnight dexamethasone suppression. Plasma progesterone (Po), 17α-hydroxyprogesterone (17Po), and cortisol were assayed in 65 gynaecologically normal women and in 187 with a variety of gynaecological problems including dysfunctional uterine bleeding, unexplained primary infertility, endometriosis, polycystic ovaries, idiopathic hirsutism, and premenstrual syndrome. Responses to ACTH were compared with those in normal subjects according to predominant diagnostic category or categories. There was a wide spectrum of progestogen response to Synacthen in all groups with close agreement between the 30- and 60-min increments in the serum levels for any one steroid. The test was reproducible from one cycle to the next for 17Po (a relatively weak progestogen) and cortisol but much less so for the strong progestogen Po. This variability was not due to spontaneous fluctuation in dexamethasone-suppressed serum Po levels and remains unexplained. The 60-min Po and 17Po increments tended to increase slightly with age. Overall, the 60-min Po increments were a little higher amongst the patients with unexplained primary infertility than amongst controls. There were no significant differences in 17Po increments between normal women and patients, with an equal incidence of marked hyperresponse (exceeding 6 nmol/l increment) in both populations. Unexpectedly, the 18 patients complaining of severe premenstrual symptoms had significantly lower cortisol responses than other groups. We conclude that except in overt 21-hydroxylase deficiency, adrenal progestogens are unlikely to be a major factor in causing gynaecological disorders