The effect of 17β-estradiol on adrenocortical sensitivity, responsiveness, and steroidogenesis in postmenopausal women

S. M. Slayden, L. Crabbe, S. Bae, H. D. Potter, Ricardo Azziz, C. R. Parker

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Abstract

Aging in women is associated with reduced production of adrenal androgens (AAs); this decrease may in part be the result of menopausal hypoestrogenism. To determine the effects of physiological concentrations of estradiol (E2) on adrenocortical sensitivity and responsiveness in postmenopausal women, we determined steroid responses to a continuous incremental ACTH-(1-24) infusion (0, 20, 40, 80, 160, 320, 640, and 1280 ng/1.5 m2/h), followed by an ACTH-(1-24) bolus of 0.25 mg, after overnight dexamethasone suppression before and after 3 months of E2 therapy (transdermal E2, 0.05 mg/day) in 14 postmenopausal women. After E2 treatment, subjects demonstrated an increase in serum E2 concentrations from 29.8 ± 2.6 to 49.9 ± 6.0 pg/mL (P < 0.005) and a decline in mean FSH levels from 83.1 ± 24.4 to 57.5 ± 17.3 mIU/mL (P < 0.004). E2 administration had no effect on basal, postdexamethasone, or maximally stimulated serum levels of cortisol (F), dehydroepiandrosterone (DHEA), androstenedione (A4), or 17- hydroxyprogesterone (17-OHP). Furthermore, E2 did not affect adrenal sensitivity or responsiveness to ACTH-(1-24) stimulation. Finally, the steroid ratios reflecting 3β-hydroxysteroid dehydrogenase (i.e. the A4/DHEA ratio) and Δ4/17,20-lyase (i.e. the A4/17-OHP ratio) activities also were unaffected by E2 therapy. The responsiveness of F to ACTH was significantly greater than that of DHEA, A4, or 17-OHP regardless of the circulating E2 levels. Furthermore, F and A4 were significantly more sensitive to ACTH stimulation than were 17-OHP and DHEA, and this was not altered by E2 administration. We conclude that transdermal E2 replacement to postmenopausal women does not significantly alter AA sensitivity or responsiveness to ACTH. Hence, it is unlikely that the hypoestrogenism of menopause contributes to the decline in AAs noted with age. Furthermore, menopausal estrogen replacement, at least in physiological amounts administered transdermally, cannot be expected to reverse the suppressed production of these androgens.

Original languageEnglish (US)
Pages (from-to)519-524
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume83
Issue number2
DOIs
StatePublished - Nov 11 1998

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Dehydroepiandrosterone
Cosyntropin
Androgens
Estradiol
Adrenocorticotropic Hormone
3-Hydroxysteroid Dehydrogenases
Steroids
Steroid 17-alpha-Hydroxylase
17-alpha-Hydroxyprogesterone
Estrogen Replacement Therapy
Androstenedione
Menopause
Serum
Dexamethasone
Hydrocortisone
Estrogens
Therapeutics
Aging of materials

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

The effect of 17β-estradiol on adrenocortical sensitivity, responsiveness, and steroidogenesis in postmenopausal women. / Slayden, S. M.; Crabbe, L.; Bae, S.; Potter, H. D.; Azziz, Ricardo; Parker, C. R.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 83, No. 2, 11.11.1998, p. 519-524.

Research output: Contribution to journalArticle

Slayden, S. M. ; Crabbe, L. ; Bae, S. ; Potter, H. D. ; Azziz, Ricardo ; Parker, C. R. / The effect of 17β-estradiol on adrenocortical sensitivity, responsiveness, and steroidogenesis in postmenopausal women. In: Journal of Clinical Endocrinology and Metabolism. 1998 ; Vol. 83, No. 2. pp. 519-524.
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