What is the function of Dehydroepiandrosterone sulfate (DHEA-S) and its origin?

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From the Guidelines

DHEA-S is a steroid hormone primarily produced by the adrenal glands, serving as a precursor to both male and female sex hormones and playing important roles in immune function, brain health, and bone density maintenance. The production of DHEA-S originates from cholesterol through a series of enzymatic reactions in the adrenal glands, with smaller amounts also being produced in the gonads and brain 1. Its function as the most abundant circulating steroid hormone in the human body is crucial, and it acts as a storage form of DHEA due to its sulfate group, allowing it to remain in the bloodstream longer. Key aspects of DHEA-S include:

  • Its peak levels in early adulthood, around age 20-30, followed by a gradual decline with age
  • Its potential role in anti-aging, although the clinical significance of its decline remains debated
  • The importance of medical supervision for supplementation due to potential effects on hormone balance and interactions with certain conditions or medications
  • The use of blood tests to measure DHEA-S levels for evaluating adrenal function or investigating hormonal imbalances, as seen in patients with primary adrenal insufficiency (PAI) who may require DHEA replacement therapy 1.

From the Research

DHEA-s Function and Origin

  • DHEA-s, or dehydroepiandrosterone sulfate, is a sulfated form of dehydroepiandrosterone (DHEA), an androgen produced by the zona reticularis of the adrenal gland 2.
  • DHEA is an abundant circulating androgen precursor preferentially produced by the adrenal glands 3.
  • The exact physiological role of DHEA is not yet fully understood, but it has been shown to exert its effects via downstream conversion to sex steroid hormones, neuromodulation, improvement in endothelial cell function, and possibly by acting on a cell membrane-bound receptor 3.

Effects of DHEA Deficiency

  • DHEA deficiency is associated with morbidity, including adverse impacts on metabolic function, quality of life, and sexuality in multiple studies 2.
  • Low levels of circulating DHEA have been demonstrated in women with diminished libido and other symptoms of sexual dysfunction 3.
  • DHEA deficiency has also been associated with various drugs, and endocrine, nonhormonal, and age-related disorders 3.

Benefits of DHEA Supplementation

  • DHEA supplementation has been shown to produce beneficial effects in women with adrenal insufficiency, including improved well-being, sexual satisfaction, and insulin sensitivity 4.
  • DHEA replacement in patients with adrenal insufficiency positively influences mood, sexuality, and subjective health status 5.
  • DHEA may also have immunomodulatory effects, and its low levels correlate with increased cardiovascular disease and all-cause mortality 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The role for long-term use of dehydroepiandrosterone in adrenal insufficiency.

Current opinion in endocrinology, diabetes, and obesity, 2022

Research

Dehydroepiandrosterone therapy as female androgen replacement.

Seminars in reproductive medicine, 2006

Research

Is DHEA replacement beneficial in chronic adrenal failure?

Best practice & research. Clinical endocrinology & metabolism, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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