When both DHEA (or its sulfated form, DHEA-S) and testosterone are elevated at the same time, the most common explanation in women of reproductive age is polycystic ovary syndrome, though the list of possible causes stretches well beyond that single diagnosis. Because DHEA is a precursor molecule that the body converts into testosterone and other active hormones, anything that floods the system with DHEA can drag testosterone up with it, and some conditions independently crank up production from both the adrenal glands and the ovaries simultaneously. Sorting out why both hormones are high matters, because the underlying cause shapes both the symptoms you experience and the treatment that actually helps.
How DHEA and Testosterone Are Connected
DHEA is made primarily in the adrenal glands, with a smaller contribution from the ovaries (and the testes in men). Once released, it circulates mostly as DHEA-S, an inactive reservoir. Peripheral tissues then convert DHEA into active androgens, including testosterone and a potent androgen called dihydrotestosterone. This conversion happens in skin, fat, muscle, and reproductive organs, meaning the body essentially builds testosterone from the DHEA raw material supplied by the adrenals.1PubMed Central. Impact of DHEA supplementation on testosterone and estradiol levels in postmenopausal women: a meta-analysis of randomized controlled trials assessing dose and duration effects That biochemical relationship explains why elevated DHEA so often appears alongside elevated testosterone: more precursor, more end product.
The flip side also exists. Under certain conditions, testosterone itself can stimulate adrenal DHEA-S production. Research in primates has shown that administering testosterone raised circulating DHEA-S to levels resembling those of younger animals, suggesting the relationship between the two hormones runs in both directions.2PubMed Central. Testosterone increases circulating dehydroepiandrosterone sulfate levels in the male rhesus macaque This two-way feedback helps explain why the combination of high DHEA and high testosterone is so persistent once it develops.
Polycystic Ovary Syndrome
PCOS is far and away the most frequent reason a woman’s blood work comes back with both DHEA-S and testosterone running high. A subgroup of women with PCOS have excessive adrenal androgen production layered on top of the ovarian androgen excess that defines the condition. In a study of young women with PCOS, about a third had elevated DHEA-S levels above 3 mcg/mL, and those women also had higher testosterone and androstenedione than PCOS patients whose DHEA-S was normal.3PubMed Central. Increased Prevalence of Elevated DHEAS in PCOS Women with Non-Classic (B or C) Phenotypes: A Retrospective Analysis in Patients Aged 20 to 29 Years In other words, within an already hyperandrogenic condition, adrenal overproduction makes things measurably worse.
The severity tracks with the hormonal profile. In PCOS women with the more severe phenotypes, high androstenedione levels correlated positively with testosterone, DHEA-S, and the ratio of LH to FSH, the hormonal imbalance that drives much of the ovarian dysfunction in PCOS.4PubMed. Elevated serum androstenedione is associated with a more severe phenotype in women with polycystic ovary syndrome (PCOS) The practical takeaway is that if you have PCOS and your DHEA-S is also elevated, you may be dealing with a more aggressive hormonal pattern than someone whose excess androgens come from the ovaries alone.
Insulin resistance amplifies the problem. In PCOS, insulin has a positive and significant relationship with both LH and testosterone: as insulin goes up, so do those two hormones. Meanwhile, insulin has the opposite relationship with sex hormone-binding globulin (SHBG), the protein that locks up testosterone and keeps it inactive. Higher insulin means lower SHBG, which means more free testosterone circulating and causing symptoms even if total testosterone looks only mildly elevated on paper.5PubMed Central. Influence of Insulin on LH, Testosterone and SHBG in various PCOS Categories based on the Mode of Secretion of LH in relation to FSH Levels
Non-Classic Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia (CAH) is a group of inherited enzyme deficiencies that disrupt adrenal hormone production. The non-classic form, which is much milder than the version detected at birth, is a stealth cause of combined high DHEA and high testosterone that is often mistaken for PCOS. In non-classic CAH caused by partial 21-hydroxylase deficiency, cortisol production is roughly normal or only slightly low, but the adrenal glands pump out excessive androgens, including a class called 11-oxygenated androgens that have only recently been recognized as clinically important.6PubMed Central. Nonclassic Congenital Adrenal Hyperplasia: What Do Endocrinologists Need to Know?
About 95% of all CAH cases trace to mutations in the CYP21A2 gene. When enzyme activity is between roughly 20% and 70% of normal, the result is the non-classic form: enough enzyme function to avoid a cortisol crisis, but not enough to prevent androgens from building up.7Ginekologia Polska. A recent overview of non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: pathophysiology, recognition, and management Women with this form typically show up in their teens or twenties with acne, irregular periods, and excess body hair, which is exactly the same presentation as PCOS. The key diagnostic difference is a stimulated 17-hydroxyprogesterone test, which runs abnormally high in CAH but not in PCOS.
Some patients with non-classic 21-hydroxylase deficiency also have enhancement of what researchers call the “backdoor pathway,” an alternative route through which adrenal precursors are converted to dihydrotestosterone without going through the usual testosterone intermediate. This pathway can operate in the adrenals, in peripheral tissues, or both, and it can drive virilization even when standard testosterone measurements look only modestly elevated.8PubMed Central. Non-Classic Disorder of Adrenal Steroidogenesis and Clinical Dilemmas in 21-Hydroxylase Deficiency Combined with Backdoor Androgen Pathway. Mini-Review and Case Report
Adrenal and Ovarian Tumors
Tumors are a much less common cause than PCOS or CAH, but they’re the reason clinicians take very high androgen levels seriously. Androgen-secreting adrenal tumors are rare overall and raise suspicion for adrenocortical carcinoma. These tumors tend to overproduce more than one androgen at a time, which is why blood work often shows elevations in testosterone, DHEA, DHEA-S, and androstenedione all at once. They occur more frequently in women than men and can cause rapid-onset hirsutism on the face, chest, and back, along with acne, irregular cycles, and sometimes clitoral enlargement or hypertension.9PubMed Central. Isolated DHEAS production by an adrenal neoplasm: Clinical, biochemical and pathologic characteristics
Ovarian tumors that produce androgens deserve separate mention because they present differently on lab work. In case reports of ovarian Leydig cell tumors and thecomas, testosterone was markedly elevated while DHEA-S and androstenedione were normal or even below the reference range, pointing to the ovary rather than the adrenal gland as the source.10PubMed. Diagnostic pitfalls in ovarian androgen-secreting tumors in postmenopausal women with rapidly progressed severe hyperandrogenism The speed of symptom onset is a key clinical clue: tumor-driven androgen excess tends to progress over weeks to months, whereas PCOS and CAH develop gradually over years. Any postmenopausal woman with rapidly worsening virilization deserves urgent imaging and potentially surgery.
Cushing’s Syndrome and Excess ACTH
ACTH, the pituitary hormone that tells the adrenal glands to produce cortisol, also stimulates adrenal androgen output. In Cushing’s syndrome, whether caused by a pituitary tumor (Cushing’s disease) or by an ectopic ACTH-producing tumor elsewhere in the body, the chronic oversupply of ACTH drives the adrenals to overproduce both cortisol and androgens. Steroid profiling studies have confirmed that patients with Cushing’s disease and ectopic ACTH tumors show elevated levels of androgens and their metabolites compared to healthy controls.11PubMed. Serum steroid profiling in Cushing’s syndrome patients
In practice, Cushing’s produces a distinctive clinical picture: weight gain concentrated around the trunk and face, easy bruising, thin skin, high blood pressure, and muscle weakness, alongside the androgen-driven symptoms like acne and hirsutism. Because cortisol and androgens are both elevated, the combination of a Cushingoid appearance with signs of androgen excess should prompt specific testing for cortisol overproduction.
Hyperprolactinemia
Prolactin, the hormone best known for stimulating breast milk production, has an underappreciated relationship with adrenal androgens. Women with elevated prolactin levels, whether from a prolactin-secreting pituitary tumor (prolactinoma) or from chronic use of certain psychiatric medications, have significantly higher DHEA and DHEA-S levels than untreated controls. The same pattern has been observed in men with prolactinomas.12The Journal of Clinical Endocrinology & Metabolism. EFFECT OF PROLACTIN ON PLASMA DHEA(S) LEVELS
The mechanism appears to be a direct effect on the adrenal gland. Lab work using cultured human adrenal cells showed that prolactin, when combined with ACTH, amplified the secretion of DHEA-S and DHEA beyond what ACTH alone produced. Prolactin did not have this effect by itself, and it did not increase cortisol, which suggests a targeted synergy with ACTH specifically for adrenal androgen production.13The Journal of Clinical Endocrinology & Metabolism. Prolactin Has a Direct Effect on Adrenal Androgen Secretion If you have unexplained elevations in DHEA-S alongside symptoms like irregular periods or galactorrhea (unexpected breast milk), checking a prolactin level is worth discussing with your doctor.
DHEA Supplements and Other Exogenous Sources
DHEA is sold over the counter as a supplement in many countries, and taking it will predictably raise both DHEA-S and testosterone. A study of middle-aged men found that a single oral dose of DHEA raised circulating DHEA-S and free testosterone well above baseline during recovery from high-intensity exercise, although total testosterone did not change significantly.14PubMed. Effect of acute DHEA administration on free testosterone in middle-aged and young men following high-intensity interval training The distinction between free and total testosterone matters here: free testosterone is the fraction available to act on tissues, and it can spike even when the total number looks stable.
This is relevant for anyone taking DHEA supplements for anti-aging, libido, or athletic performance. If your lab work comes back with high DHEA-S and high testosterone and you are supplementing with DHEA, the supplements are the most likely explanation. Stopping them for a few weeks and retesting typically resolves the question. It’s also worth noting that in the context of meta-analyses on postmenopausal women, DHEA supplementation reliably increases both testosterone and estradiol, since the same precursor feeds both pathways.1PubMed Central. Impact of DHEA supplementation on testosterone and estradiol levels in postmenopausal women: a meta-analysis of randomized controlled trials assessing dose and duration effects
A Rare Genetic Cause Worth Knowing About
Most causes of combined high DHEA and high testosterone involve overproduction. But there is a rare genetic condition where the problem is underprocessing. PAPSS2 is the enzyme that supplies the sulfate donor needed for SULT2A1, the enzyme responsible for converting DHEA into its inactive storage form, DHEA-S. When PAPSS2 is deficient due to inactivating mutations, the body cannot sulfate DHEA efficiently. Unsulfated DHEA then gets shunted toward conversion into active androgens like testosterone, causing androgen excess with the paradoxical lab finding of low DHEA-S but elevated DHEA and testosterone.15PubMed. Inactivating PAPSS2 Mutations in a Patient with Premature Pubarche
This was first described in a girl who presented with premature pubic hair development and went on to develop hyperandrogenic anovulation resembling PCOS. Further family studies confirmed the genetic basis and showed that the mutations abolished the ability of PAPSS2 to support DHEA sulfation in the lab.16PubMed Central. PAPSS2 deficiency causes androgen excess via impaired DHEA sulfation–in vitro and in vivo studies in a family harboring two novel PAPSS2 mutations PAPSS2 deficiency is exceedingly rare, but it illustrates an important principle: the balance between DHEA, DHEA-S, and downstream androgens depends on the machinery that processes these hormones, not just the glands that produce them.
Life Stages That Shift the Balance
Not every elevation in DHEA and testosterone reflects disease. Adrenarche, the natural ramping-up of adrenal androgen production, begins in early childhood and is best tracked by a rise in DHEA-S. When adrenarche happens earlier than expected (premature adrenarche), children develop pubic hair, body odor, and sometimes mild acne before the typical age. Affected children have an increased growth rate, and their DHEA-S and testosterone levels climb to ranges normal for early female puberty.17PubMed Central. Normal and Premature Adrenarche In most cases this is benign, though it does warrant monitoring to rule out more serious causes.
Exercise can also transiently raise DHEA. Research on older adults found that DHEA levels increased immediately after an exercise bout. Interestingly, DHEA-S levels increased only in females, while cortisol actually dropped, suggesting that acute physical stress triggers a brief spike in adrenal androgen output.18PubMed Central. DHEA, DHEA-S and cortisol responses to acute exercise in older adults in relation to exercise training status and sex These exercise-related bumps are temporary and clinically unimportant on their own, but they can confuse a single lab draw taken shortly after a workout.
How Clinicians Figure Out the Source
When blood work shows both DHEA-S and testosterone running high, the diagnostic question is whether the androgens are coming from the adrenal glands, the ovaries, or both. DHEA-S is produced almost exclusively by the adrenals, so a markedly elevated DHEA-S points toward an adrenal source. Total testosterone can come from either the ovaries or the adrenals, but when it is high alongside normal DHEA-S, an ovarian source is more likely. Free testosterone measurements, calculated or measured by equilibrium dialysis, are considered more useful for detecting subtler forms of androgen excess than total testosterone alone.
The pattern of elevation matters as much as the degree. A DHEA-S above roughly 700 mcg/dL in a woman raises concern for an adrenal tumor and warrants imaging. A testosterone above approximately 200 ng/dL, especially with normal DHEA-S, raises concern for an ovarian tumor. Moderate elevations of both with a clinical picture of irregular periods, acne, and excess hair growth are most consistent with PCOS or non-classic CAH. The 17-hydroxyprogesterone stimulation test separates the two: an exaggerated response confirms CAH, while a normal response favors PCOS.
Clinicians also look at the speed of symptom progression. Gradual onset over months or years suggests a functional cause like PCOS. Rapid virilization over weeks, especially with voice deepening or clitoral enlargement, is a red flag for a tumor. Checking cortisol, prolactin, and fasting insulin alongside androgens helps catch the less obvious drivers like Cushing’s syndrome, hyperprolactinemia, and insulin resistance that compound the problem.
When Symptoms Overlap and Diagnoses Blur
One of the frustrating realities of this topic is how much clinical overlap exists among the conditions that cause high DHEA and high testosterone. Hirsutism is the most common presenting complaint across the board, whether the cause is PCOS, non-classic CAH, or an adrenal tumor. Acne and menstrual irregularity are nearly universal. The phenotypic overlap is so thorough that clinical appearance alone is not enough to separate these conditions; the lab work and sometimes imaging have to do the heavy lifting.
Adding to the complexity, some of these conditions coexist. A woman can have PCOS and non-classic CAH simultaneously. Insulin resistance, which worsens PCOS, can also aggravate the hormonal profile in CAH. Hyperprolactinemia can push adrenal androgens higher in a woman who already has PCOS. Each additional driver compounds the androgen excess, and treatment may need to address more than one mechanism to get symptoms under meaningful control.
For anyone navigating this, the most practical advice is to resist the pull of a single lab number in isolation. DHEA-S and testosterone are useful signposts, but interpreting them requires context: your age, symptom timeline, medication and supplement history, other hormone levels, and sometimes genetic testing or imaging. The combination of elevated DHEA and testosterone is a starting point for investigation, not a diagnosis in itself.