Does DHEA Improve Ovarian Reserve and Fertility?

As far as fertility supplements go, we've noticed some fall in and out of fashion over time. DHEA is certainly one that's "in vogue" right now — especially among older IVF patients and those with low AMH (a proxy for low ovarian reserve). 

It's also been a highly controversial topic within the scientific and clinical community: this Washington Post article does a good job explaining how one doctor who owns a company that sells this supplement has done a lot to push DHEA, despite early and inconsistent evidence that it actually works.

When we reviewed the research, it's unfortuantely true: the studies on DHEA are very early and inconsistent. DHEA supplementation may help improve markers of ovarian reserve, but it does not seem to impact the holy grail outcome: having a healthy pregnancy and baby. 

To make sense of whether DHEA should become a fertility supplement staple or not, it's important to understand (1) how DHEA works in theory to improve fertility and (2) what the high-quality evidence shows about how it works in practice.

Let's break down both.

DHEA is a precursor hormone (think: trigger hormone) for androgens and estrogen. DHEA is specifically thought to be useful because of its link to the androgen, testosterone.

Testosterone is crucial for the early stages of recruiting, growing, and developing follicles into healthy eggs. But circulating androgen/testosterone levels decline with age, and this decline is one reason why ovarian reserve declines over time. 

The hypothesis behind DHEA supplementation is that by increasing levels of testosterone (along with something called IGF-1), DHEA might help enhance follicle growth, egg quality, ovarian reserve, and AMH production (see, for example, PMID: 33803980).

⁠In a nutshell: DHEA supplementation => increases testosterone => improves follicle growth => enhances ovarian reserve/AMH and egg quality.  

However, high-quality evidence that this hypothetical link works in practice is lacking.

TL;DR: Very early and inconsistent studies suggest DHEA may help improve markers of ovarian reserve, but it does not seem to impact the holy grail outcome: having a healthy pregnancy and baby. 

If you want to get nerdy about the studies: 

• Though some studies have shown a potential benefit of DHEA supplementation on markers of ovarian reserve, if we look holistically at data from placebo-controlled, double-blind trials that have reported on live birth rates amongst women with poor ovarian reserve, results are disappointing, and do not suggest that DHEA supplementation benefits your chances of getting pregnant. 
  
• Numerous meta-analyses exist on the topic, but findings are conflicting due to different study inclusion criteria, different IVF protocols, and definitions of "poor ovarian reserve." Interestingly, there is nearly the same number of meta-analyses as there are randomized trials, which strongly indicates that more randomized trials are needed (not more meta-analyses!).
  
• In the most recent and largest randomized trial, DHEA supplementation did not improve live birth rates amongst 821 women with poor ovarian reserve. However, it is tough to draw definitive conclusions because the population's average age was 39 years, the overall prognosis was low, and there was no fixed supplementation duration.

Because there is a plausible theoretical connection between DHEA supplementation and improved ovarian reserve, your doctor may suggest you take it, especially if you're preparing for IVF.

But because of how it works, it is not a supplement to just "add to your routine" on a whim: it's important to talk to your doctor before taking this one. This is because, as a precursor hormone, DHEA can directly impact your fertility hormones and may worsen certain fertility conditions.

Do you have endometriosis? Read this: DHEA is a precursor to multiple reproductive hormones, including estrogen. Estrogen can worsen the impact and symptoms of endometriosis and may increase the inflammatory response from endometriosis tissue. For this reason, many doctors do not recommend DHEA to women with endometriosis.

Are you a professional athlete? Read this: As a precursor to steroid hormones, DHEA is classified as an anabolic agent and is therefore prohibited by the World Anti-Doping Agency (WADA). This is relevant to any athlete governed by WADA regulations.