Dehydroepiandrosterone (DHEA) and Testosterone are both androgens with distinct origins. DHEA is primarily produced by the adrenal glands and is often measured as its sulfated form, DHEA-S, which circulates as a precursor hormone. Testosterone is predominantly secreted by the ovaries in women and the testes in men. The simultaneous finding of high DHEA-S and high Testosterone levels is medically significant because it points toward a problem in the body’s androgen production pathways. Investigation is required to determine the source of the excess androgen production.
Adrenal Gland Sources of Simultaneous Elevation
Conditions originating in the adrenal glands often cause the most dramatic elevations in DHEA-S. Congenital Adrenal Hyperplasia (CAH) is a key example, caused by a genetic deficiency in the 21-hydroxylase enzyme. This deficiency impairs cortisol production, causing the pituitary gland to release excessive Adrenocorticotropic Hormone (ACTH). ACTH hyper-stimulates the adrenal gland, shunting accumulating hormone precursors into the androgen production pathway. This surge results in very high DHEA levels, which are then converted into potent androgens like Testosterone.
Adrenal tumors, both benign adenomas and malignant carcinomas, can also autonomously secrete androgens, leading to extremely high DHEA-S levels. These tumors function independently of normal regulatory controls. A DHEA-S level exceeding 6000 ng/ml is a strong indicator of a potential adrenal tumor, although such tumors are rare. Extremely high DHEA-S is considered a red flag for adrenal pathology, as the adrenal gland is the primary source of this sulfated androgen.
Ovarian and Pituitary-Driven Hormonal Imbalances
The most common cause of high Testosterone and mild DHEA-S elevation stems from the ovaries. Polycystic Ovary Syndrome (PCOS) is the predominant condition, characterized by ovarian tissue overproducing androgens. High levels of Luteinizing Hormone (LH) and insulin stimulate ovarian cells to produce excessive Testosterone. Testosterone is typically the dominant elevated hormone in PCOS. DHEA-S is elevated in only 30 to 40 percent of affected women, and these levels are usually milder than those seen in primary adrenal disorders.
A much rarer cause involves Sertoli-Leydig cell tumors of the ovary. These tumors primarily secrete large quantities of Testosterone, leading to dramatically elevated Testosterone levels while DHEA-S often remains normal or only slightly increased. This distinct hormonal signature helps differentiate an ovarian tumor from an adrenal cause.
Cushing Syndrome, caused by prolonged exposure to high cortisol, also impacts androgen levels. The hormonal pattern depends on the cause. Pituitary-driven Cushing’s Disease, where the pituitary overproduces ACTH, often results in normal to slightly elevated DHEA-S because ACTH stimulates adrenal androgen release. Conversely, Cushing Syndrome caused by a cortisol-secreting adrenal adenoma suppresses ACTH, leading to low DHEA-S levels.
External and Lifestyle Contributions
External factors, such as supplements and medications, can directly influence DHEA-S and Testosterone levels. Over-the-counter DHEA supplements directly elevate DHEA-S concentrations. Since DHEA is a precursor, supplementation inevitably increases Testosterone levels as the body converts the excess DHEA. Testosterone replacement therapies also directly increase circulating Testosterone. Any unprescribed hormone use must be ruled out before pursuing a diagnosis of internal disease.
Certain medications can alter hormone metabolism. For instance, the anticonvulsant valproate is associated with higher DHEA-S concentrations. Conversely, some enzyme-inducing anticonvulsants, such as carbamazepine, can increase the clearance of sex hormones.
Lifestyle factors, most notably severe obesity and associated insulin resistance, also contribute to hormonal dysregulation. Excess body fat contains an enzyme that converts hormone precursors into active androgens. Hyperinsulinemia stimulates androgen production in the ovaries and adrenals, and these metabolic forces can independently raise both DHEA-S and Testosterone levels.