Experts have concerns about the use of DHEA, particularly because long-term safety data do not exist.

Side effects at high intakes (50–200 mg per day) appear to be acne (in over 50% of people), increased facial hair (18%), and increased perspiration (8%). In a preliminary trial, DHEA was also reported to induce less common side effects, including breast tenderness, weight gain, mood alteration, headache, oily skin, and menstrual irregularity in some people.¹¹ Since this trial was not controlled, some of these less common “side effects” might have occurred even with a placebo. A case of mania has been reported in an older man who took 200–300 mg of DHEA per day for six months.¹² However, in that case report, other causes of mania could not be ruled out.

Significant increases in testosterone levels in both men and women have been reported in some trials.^{13, 14} Other reports have found this change in women but not in men.¹⁵ An increase in testosterone might increase the risk of several cancers, and high amounts of DHEA have caused cancer in animals.^{16, 17} Moreover, a possible link between higher DHEA levels and risks of prostate cancer in humans has been reported.¹⁸ At least one person with prostate cancer has been reported to have had a worsening of his cancer, despite feeling better, while taking very high amounts (up to 700 mg per day) of DHEA.¹⁹

While younger women with breast cancer may have low levels of DHEA, postmenopausal women with breast cancer appear to have high levels of DHEA, which has researchers concerned.^{20, 21} Most,^{22, 23, 24, 25, 26} but not all, studies^{27, 28, 29} have found that as DHEA blood levels increase, so does the risk of breast cancer.

Supplementation with high levels of DHEA (100 mg per day) has adversely affected other indicators of cancer risk in both women and men.^{30, 31} Elevated DHEA levels have been reported to be associated with both higher,³² and lower risk for ovarian cancer.³³ The reason for this discrepancy is unknown.

The lack of knowledge about how DHEA supplementation might affect cancer risks provides a reason for caution. Until more is known, people with breast or prostate cancer or a family history of these conditions should avoid supplementing with DHEA.

Although anticancer effects of DHEA have also been reported,³⁴ they involve trials using animals that do not process DHEA the way humans do. Therefore, these positive effects may have no relevance for people.

Some doctors recommend that people taking DHEA have liver enzymes measured routinely. Anecdotes of DHEA supplementation (of at least 25 mg per day) leading to heart arrhythmias have appeared.³⁵

The relationship between DHEA, blood pressure, and heart disease is poorly understood. Increased blood levels of DHEAS have been associated with increased blood pressure³⁶ and other cardiovascular risk factors in some,³⁷ but not all,³⁸ studies. One study found that people with hypertension had significantly decreased blood levels of DHEA.³⁹ Until clinical trials clear up these inconsistencies and confirm its safety, people with hypertension should avoid using DHEA, except under the close supervision of a doctor.

At only 25 mg per day, DHEA has lowered HDL cholesterol while increasing insulin-like growth factor (IGF).⁴⁰ Decreasing HDL could increase the risk of heart disease. Increasing IGF might increase the risk of breast cancer.