Is oral dehydroepiandrosterone (DHEA) appropriate for treating hypoactive sexual desire syndrome in adults over 40 with low endogenous DHEA‑S levels?

Oral DHEA for Hypoactive Sexual Desire Disorder

Oral DHEA at 100 mg daily may be considered for postmenopausal women over 40 with HSDD and documented low DHEA-S levels, particularly when concurrent dyspareunia is present, though vaginal DHEA (prasterone) is preferred over oral administration, and FDA-approved alternatives like flibanserin should be considered first-line.

Evidence-Based Treatment Algorithm

First-Line Considerations

• FDA-approved medications (flibanserin or bremelanotide) should be considered as initial therapy for postmenopausal women with HSDD before DHEA 1
• Flibanserin results in approximately 1 additional satisfying sexual event every 2 months in premenopausal women, with preliminary data suggesting efficacy in breast cancer survivors on endocrine therapy 2, 3

Role of DHEA Therapy

Vaginal vs. Oral Administration:

• Vaginal DHEA (prasterone) is the preferred route when dyspareunia coexists with HSDD, as it improves sexual desire, arousal, pain, and overall sexual function 2, 1
• A randomized trial of 464 cancer survivors showed vaginal DHEA led to significant improvements across multiple sexual function domains 2
• Vaginal testosterone cream may be a safer alternative to systemic administration, particularly in cancer survivors 1

Oral DHEA Evidence:

• The most rigorous placebo-controlled trial (93 postmenopausal women, 52 weeks, 50 mg daily) showed no significant improvement in satisfying sexual events or sexual function scores compared to placebo 4
• However, a smaller study (27 postmenopausal women, 6 weeks, 100 mg daily) demonstrated significant improvements in sexual arousal (p=0.001) and satisfaction (p<0.05) in women only, with no efficacy in men 5
• The beneficial effects appear mediated through DHEA's conversion to bioavailable testosterone, which increased significantly in women but not men 5
• A separate study of early postmenopausal women using 10 mg daily for 1 year showed improvement in sexual function and frequency compared to vitamin D 6

Critical Dosing Distinction

• Doses of 50 mg daily appear ineffective for sexual function improvement 4
• Doses of 100 mg daily or higher may be necessary to achieve therapeutic benefit in women with HSDD 5
• Lower doses (10 mg daily) showed benefit in early postmenopausal women but require further validation 6

Important Clinical Caveats

Safety Concerns:

• Use vaginal DHEA with caution in patients on aromatase inhibitor therapy, as it increases circulating androgens that may impact AI activity 2
• Safety of vaginal hormones has not been firmly established in survivors of estrogen-dependent cancers 2
• Oral DHEA at 50 mg daily causes androgenic side effects including acne and increased hair growth 4

Patient Selection:

• Oral DHEA may be most appropriate for postmenopausal women with documented low DHEA-S levels who have failed or cannot tolerate FDA-approved alternatives 5
• Women >70 years old may experience additional benefits including improved bone turnover and skin status at 50 mg daily 7
• Men with HSDD do not benefit from DHEA therapy and should not be treated with this approach 5

Monitoring Requirements

• Measure baseline DHEA-S and bioavailable testosterone levels before initiating therapy 5
• Monitor for androgenic side effects (acne, hirsutism) throughout treatment 4
• Reassess sexual function at 6 weeks using validated questionnaires 5
• If using doses of 50 mg or higher, ensure no harmful accumulation of active steroids 7