Dehydroepiandrosterone sulfate levels throughout life in human males and females

Adrenopause is the decline in

secretion Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mec ...

and levels of

adrenal androgen Adrenal steroids are steroids that are derived from the adrenal glands. They include corticosteroids, which consist of glucocorticoids like cortisol and mineralocorticoids like aldosterone, adrenal androgens like dehydroepiandrosterone (DHEA), DHE ...

s such as

dehydroepiandrosterone Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It funct ...

(DHEA) and

dehydroepiandrosterone sulfate Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA-S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. It is the 3β-sulfate ester and a metabolite of dehydroepia ...

(DHEA-S) from the

zona reticularis The zona reticularis (sometimes, reticulate zone) is the innermost layer of the adrenal cortex, lying deep to the zona fasciculata and superficial to the adrenal medulla. The cells are arranged cords that project in different directions giving a n ...

of the

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal corte ...

s with age. Levels of adrenal androgens start to increase around age 7 or 8 years (

adrenarche Adrenarche is an early stage in sexual maturation that happens in some higher primates (including humans), typically peaks at around 20 years of age, and is involved in the development of pubic hair, body odor, skin oiliness#Oily skin, skin oiline ...

), 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. It is caused by the progressive

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

of adrenal androgen-secreting

cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

s and hence

involution Involution may refer to: Mathematics * Involution (mathematics), a function that is its own inverse * Involution algebra, a *-algebra: a type of algebraic structure * Involute, a construction in the differential geometry of curves * Exponentiati ...

of the zona reticularis. It is analogous to andropause in men and

menopause Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...

in women, the abrupt or gradual decline in production of

sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects a ...

s from the

gonad A gonad, sex gland, or reproductive gland is a Heterocrine gland, mixed gland and sex organ that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gon ...

s with age. DHEA can be supplemented or taken as a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

in the form of

prasterone Prasterone, also known as dehydroepiandrosterone (DHEA) and sold under the brand name Intrarosa among others, is a medication as well as over-the-counter dietary supplement which is used to correct DHEA deficiency due to adrenal insufficie ...

to replace adrenal androgens later in life if it is desired. Some clinical studies have found benefits of DHEA supplementation in the

elderly Old age is the range of ages for people nearing and surpassing life expectancy. People who are of old age are also referred to as: old people, elderly, elders, senior citizens, seniors or older adults. Old age is not a definite biological sta ...

and people with

adrenal insufficiency Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal glands—also referred to as the adrenal cortex—normally secrete glucocorticoids (primarily cortisol), mineraloco ...

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.

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.

References

Developmental stages Endocrine system {{Biology-stub

Comparative Endocrinology

Mechanisms Underlying Adrenopause

Clinical Implications

Therapeutic Considerations

See also

References