Adrenopause

Not to be confused with Andropause.

Adrenopause is the decline in secretion and levels of adrenal androgens such as dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) from the zona reticularis of the adrenal glands with age.^[2][3] Levels of adrenal androgens start to increase around age 7 or 8 years (adrenarche), peak in early adulthood around age 20 to 25 years, and decrease at a rate of approximately 2% per year thereafter, eventually reaching levels of 10 to 20% of those of young adults by age 80 years.^[2][1] It is caused by the progressive apoptosis of adrenal androgen-secreting cells and hence involution of the zona reticularis.^[2][3] It is analogous to andropause in men and menopause in women, the abrupt or gradual decline in production of sex hormones from the gonads with age.^[4]

Levels of DHEA-S, a major adrenal androgen, throughout life in humans.^[1]

DHEA can be supplemented or taken as a medication in the form of prasterone to replace adrenal androgens later in life if it is desired.^[2] Some clinical studies have found benefits of DHEA supplementation in the elderly and people with adrenal insufficiency.^[2]

Comparative Endocrinology

Adrenopause is analogous to other endocrine aging phenomena:

• Menopause: The cessation of ovarian estrogen and progesterone production in women.
• Andropause: The gradual decline in testicular testosterone production in men.

These processes collectively underscore the broader concept of endocrine senescence, reflecting the systemic nature of hormonal aging.

Mechanisms Underlying Adrenopause

The decline in adrenal androgen production with age is attributed to several factors:

• Apoptosis of Adrenal Cells: Age-related programmed cell death in the adrenal cortex reduces the number of androgen-secreting cells.
• Involution of the Zona Reticularis: Structural changes and shrinkage in this adrenal zone diminish its functional capacity.
• Altered ACTH Responsiveness: The adrenal glands' responsiveness to ACTH may decrease, leading to reduced stimulation of androgen synthesis.

These changes collectively contribute to the observed decrease in circulating DHEA and DHEA-S levels in older individuals.^[5]

Clinical Implications

While the decline in adrenal androgens is a natural aspect of aging, it has been associated with various clinical outcomes:

• Frailty and Sarcopenia: Lower DHEA levels correlate with decreased muscle mass and strength, contributing to frailty.
• Cognitive Decline: Some studies suggest a link between reduced DHEA levels and cognitive impairments, though findings are inconsistent.
• Mood Disorders: Associations between low DHEA levels and mood disturbances, including depression, have been observed.

However, the causal relationships remain under investigation, and the benefits of DHEA supplementation are not conclusively established.

Therapeutic Considerations

DHEA supplementation has been explored as a potential intervention to mitigate age-related declines in adrenal androgens. Some studies report improvements in bone density, mood, and sexual function, while others find minimal or no benefit. Moreover, concerns about long-term safety and the risk of hormone-sensitive conditions necessitate cautious evaluation. Currently, routine DHEA supplementation is not universally recommended, and its use should be individualized based on clinical assessment.

See also

• Adrenal androgen-stimulating hormone