DHEA Pre-treatment in Young Patients with Low AMH
DHEA supplementation should NOT be routinely recommended for young patients with low AMH, as the highest quality randomized controlled trials demonstrate no significant improvement in ovarian reserve markers, ovarian response, or IVF outcomes.
Evidence from Randomized Controlled Trials
The most rigorous evidence comes from double-blind, placebo-controlled trials that consistently fail to demonstrate benefit:
Primary RCT Evidence
A 2014 randomized controlled trial of 32 poor responders receiving DHEA (25mg three times daily) for at least 12 weeks showed no statistically significant differences in antral follicle count (AFC), anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), ovarian response to gonadotropin stimulation, or IVF outcomes compared to placebo 1
A 2016 double-blind RCT of 72 anticipated normal responders (AFC 5-15) receiving DHEA for 12 weeks demonstrated no significant differences in AFC, AMH, FSH, ovarian response to standard-dose stimulation, or number of oocytes obtained, despite achieving significantly higher serum DHEA-S and testosterone levels 2
Contradictory Observational Data
While some observational studies suggest potential benefit, these lack the rigor of placebo-controlled trials:
A 2010 observational study of 120 patients reported AMH improvements of approximately 60% after DHEA supplementation, with more pronounced effects in women under age 38 3
A 2014 non-blinded randomized trial showed higher follicular fluid BMP-15 levels and accumulated embryo scores in the DHEA group 4
A 2013 self-controlled study of 32 poor responders reported increased AFC without changes in AMH or inhibin B, suggesting DHEA may rescue small antral follicles from atresia 5
Critical Guideline Context for Young Patients
The interpretation of low AMH in young women requires special consideration:
In the general population, AMH peaks at approximately age 25 years, and there is no evidence that low AMH indicates reduced fertility or low ovarian reserve in females under age 25 6
Current data do not support routine AMH testing for preconception counseling in young, fecund women, and AMH testing recommendations are limited to women aged ≥25 years for whom validated normative data are available 6
AMH is inversely correlated with age in women ≥25 years, making it a clinically useful marker of ovarian reserve primarily in this age group 7
Clinical Management Algorithm
For Young Patients (<25 years) with Low AMH:
- Do not base fertility treatment decisions solely on AMH values, as normative data in this age group are limited and low AMH does not reliably predict reduced fertility 6
- Assess menstrual history, Tanner stage, and clinical signs of ovarian dysfunction 6
- Measure LH, FSH, and estradiol if there is delayed puberty, irregular menses, or amenorrhea 6
For Patients ≥25 years with Low AMH:
- Women with severely low AMH (<0.7 ng/ml) face 91% increased odds of miscarriage (OR 1.91; 95% CI 1.40-2.60) 7
- Women with AMH <1 ng/ml should pursue fertility evaluation and attempts promptly rather than delay with unproven interventions 7
- Refer to reproductive endocrinology for infertility evaluation and consideration of assisted reproduction 6
- Discuss fertility preservation options (oocyte cryopreservation) if future fertility is desired 6, 7
Common Pitfalls to Avoid
- Do not prescribe DHEA based on observational studies alone when high-quality RCTs show no benefit 1, 2
- Do not delay appropriate fertility treatment while attempting DHEA supplementation, particularly in women ≥25 years with documented diminished ovarian reserve 7
- Do not over-interpret low AMH in women under 25, as this may lead to unnecessary anxiety and interventions 6
- Recognize that different AMH assays may yield varying results, so interpret values in context of specific laboratory reference ranges 7
Specialist Referral Indications
Referral to reproductive endocrinology is warranted for: