Effects of Aging on Adrenal Function in the Human: Responsiveness and Sensitivity of Adrenal Androgens and Cortisol to Adrenocorticotropin in Premenopausal and Postmenopausal Women1
C. Richard Parker, Jr.,
Scott M. Slayden,
Ricardo Azziz,
S. Lolita Crabbe,
Gene A. Hines,
Larry R. Boots and
Sejong Bae
Departments of Obstetrics and Gynecology, Medicine, and
Biostatistics and Biomathematics, University of Alabama, Birmingham,
Alabama 35233
Address all correspondence and requests for reprints to: C. Richard Parker, Jr., Ph.D., Department of Obstetrics and Gynecology, University of Alabama, Birmingham, Alabama 35233-7333.
We sought to determine the effects of aging on several aspectsof
adrenal steroidogenesis in the hopes of characterizing thepossible
causes of adrenal androgen deficiency in elderly women.To this end, we
quantified basal morning concentrations of cortisol(F),
dehydroepiandrosterone (DHEA), dehydroepiandrosterone
sulfate(DS), and androstenedione (A4) and then evaluated the effects
ofovernight dexamethasone (DEX) suppression followed by adrenal
responsesto graded hourly infusions of ACTH, ranging from 20–1280
ng/1.5m2·h. Finally, we performed a standard 0.25-mg
ACTH bolusstimulation test, with sampling at 1 h thereafter.
Basal serumlevels of DHEA, DS, and A4 were significantly
reduced (50% each)in a group of 35 healthy postmenopausal women,
55–68 yrold, compared to those in 30 healthy, regularly menstruating
women,20–25 yr old. Post-DEX levels of these C19 steroids
alsowere significantly lower in the older women than in the younger
women;the percent decrease after DEX for A4 was greater in the older
women,whereas those in DHEA and DS were not age related.
Basal andpost-DEX levels of F were similar in both groups. Secretory
responsesof DS to ACTH were not informative due to its large plasma
pooland slow clearance rate. The maximally stimulated levels of
DHEAafter ACTH bolus were significantly lower in the
older womenthan in younger women; those of A4 were similar in both age
groups,and the maximally achieved levels of F were higher in the older
womenthan in the younger women. The sensitivity of adrenal
DHEA,A4, and F to ACTH (defined as the minimal dose of
ACTH requiredto significantly increase the steroid levels above basal
post-DEXvalues) was similar in older and younger women. The
responsivenessof the steroids of interest to ACTH (defined as the
slope ofthe dose-response curve over the linear portion of the
dose-responsecurve) also was similar among younger and older women.
Thesedata demonstrate that the deficiency in adrenal androgen
productionin women is restricted to the 5-pathway
steroid products (DHEAand DS), whereas there is no
reduction in the capacity of theadrenal to produce A4 or cortisol. As
DHEA and DS are likelyto be produced mainly in the zona
reticularis of the adrenalcortex, we propose that these data point to
an alteration inthat cortical zone as the cause of adrenal androgen
deficiencyin aging. The reductions in A4 in aging are probably due to
reducedovarian secretion after menopause.
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50% each) in a group of 35 healthy postmenopausal women,
55–68 yr old, compared to those in 30 healthy, regularly menstruating
women, 20–25 yr old. Post-DEX levels of these C19 steroids
also were significantly lower in the older women than in the younger
women; the percent decrease after DEX for A4 was greater in the older
women, whereas those in DHEA and DS were not age related.
Basal and post-DEX levels of F were similar in both groups. Secretory
responses of DS to ACTH were not informative due to its large plasma
pool and slow clearance rate. The maximally stimulated levels of
DHEA after ACTH bolus were significantly lower in the
older women than in younger women; those of A4 were similar in both age
groups, and the maximally achieved levels of F were higher in the older
women than in the younger women. The sensitivity of adrenal
DHEA, A4, and F to ACTH (defined as the minimal dose of
ACTH required to significantly increase the steroid levels above basal
post-DEX values) was similar in older and younger women. The
responsiveness of the steroids of interest to ACTH (defined as the
slope of the dose-response curve over the linear portion of the
dose-response curve) also was similar among younger and older women.
These data demonstrate that the deficiency in adrenal androgen
production in women is restricted to the 
5-pathway
steroid products (DHEA and DS), whereas there is no
reduction in the capacity of the adrenal to produce A4 or cortisol. As
DHEA and DS are likely to be produced mainly in the zona
reticularis of the adrenal cortex, we propose that these data point to
an alteration in that cortical zone as the cause of adrenal androgen
deficiency in aging. The reductions in A4 in aging are probably due to
reduced ovarian secretion after menopause. 
