Hormone replacement therapy increases ACTH/dehydroepiandrosterone sulfate in menopause
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Updated: Oct 5, 2026

An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
E Fonseca1, L Basurto, S Velázquez
1Endocrine Research Unit, Hospital de Especialidades, Centro Médico Nacional, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Objective:
To demonstrate that hypoestrogenism in menopause is in part responsible for the decrease in circulating dehydroepiandrosterone sulfate (DHEA-S) and ACTH levels. To test this hypothesis, 25 postmenopausal women aged 47-60 years, were given orally conjugated equine estrogen (CEE) to study the effect on circulating DHEA-S, cortisol and ACTH.
Design:
A prospective, non-blinded study was performed. Hormonal levels were analyzed before and after three cycles of CEE 0.625 mg/day for 21 days followed each by chlormadinone acetate for 5 days.
Results:
Low baseline levels of DHEA-S increased significantly after HRT (1.71+/-0.75 to 3.3+/-1.5 micromol/l, (P<0.001). ACTH levels augmented moderately from 3.26+/-1.4 to 4.7+/-1.8 pmol/l (P<0.05) and cortisol from 350.4+/-118 to 450.8+/-144 nmol/l (P<0.01). A positive correlation was obtained between 17 beta-estradiol and ACTH (r=0.48), estradiol and cortisol (r=0.52) as well as estradiol and DHEA-S (r=0.60). In addition, the correlation was highly significant (P<0.001) between ACTH and DHEA-S at the term of HRT.
Conclusion:
HRT increased DHEA-S, ACTH and cortisol concentrations, which may suggest that this therapy may exert a stimulatory effect on the pituitary gland when baseline hypoestrogenism is present, but further studies are required to clarify the mechanism underlying this process.
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