Androgen Supplementation in Infertile Women: Top 12 Clinical Questions from RE/OBGYN’s (and answers)
Medically Reviewed by Norbert Gleicher, MD, FACOG, FACS
Medical Director and Chief Scientist, The Center for Human Reproduction in NYC
Androgen supplementation in infertile women, especially using dehydroepiandrosterone (DHEA), a naturally occurring precursor to sex hormones remains a somewhat controversial subject, in fertility treatments. Available studies have been condemned as underpowered and of no significance. While no authoritative body has endorsed androgen supplementation due to a lack of an overwhelming prospective randomized trial, industry surveys show that over half of all IVF centers globally use androgen supplementation in at least a select group of patients.
In the 28+ studies that have been conducted, supplementing patients with low androgen levels and low ovarian reserve with DHEA has shown to:
- Improve egg/embryo numbers
- Improve egg/embryo quality
- Improve spontaneous pregnancy rates
- Improve IVF pregnancy rates
- Improve time to conception
- Improve cumulative pregnancy rates
Recently, Dr. Norbert Gleicher, Medical Director and Chief Scientist of the Center for Human Reproduction (CHR) in New York City who did the original research on DHEA and fertility, gave an update on androgen supplementation at IVF Worldwide’s “IVF Online Worldwide Congress” to not less than 13,192 reproductive endocrinologists and obstetrician-gynecologists. Dr. Gleicher noted that at CHR, the number of patients presenting on some form of androgen supplement has gone from under 5% to over 60% in the last few years. However, Gleicher concluded that patients already on DHEA supplementation are often incorrectly self-supplementing, either by dosage or timing.
After his lecture “Why and How to Supplement Androgens in Infertile Women” Gleicher received over 60+ questions from doctors regarding androgen supplementation.
Click here to watch Dr. Gleicher’s lecture in its entirety. He responds to the top 12 questions below:
- What are the best indications for dehydroepiandrosterone (DHEA) treatment?
- Low functional ovarian reserved (high FSH/low AMH) in older women or younger women with premature ovarian aging (POA)
- The Hypo-androgenic PCOS-like patient. Read more about this phenotype in these two research papers:
- Rare cases of Secondary Ovarian Insufficiency (SOI), due to insufficient production of adrenal androgens.
- What is the protocol used for dehydroepiandrosterone (DHEA) supplementation?
- We recommend in qualified patients 25mg of DHEA 3x/day for at least 6 weeks before IVF cycle start. This is a physiological replacement dosage – roughly the dosage of natural production by an adult individual. Before the IVF cycle start, testosterone should be at least in the normal to mid-range and SHBG should be below 80. DHEA is maintained uninterrupted until the patient is pregnant or stops treatment with the use of her own eggs. IVF cycle stimulation should avoid long agonists, antagonists and OVPs – everything that is suppressive on the ovaries.
- Are there adverse effects of androgens like dehydroepiandrosterone (DHEA)? What should I consider for patients’ counseling? At a dose of 25mg TID, do many patients complain of hyperandrogenism?
- Side effects of DHEA at here advocated dosages are minimal, and reported in only a small minority of patients. Most patients have no negative side effects. Negative side effects include oily skin in some women, rarely acne, and even more rarely mild hair loss. The most frequently noted side effect is a positive one: more energetic, decisive and better libido.
- Do all women who need infertility treatment need a baseline androgen work up?
- At The Center for Human Reproduction, a baseline androgen evaluation is an integral part of our initial work up. We do recommend prior androgen profiles and only treat with DHEA if androgens are in the lower third of normal range.
- At what ranges of DHEAS, DHEA, Testosterone and Free Testosterone levels do you recommend using DHEA?
- If the patient’s androgens are in the lower one-third of normal range, we consider her hypo-androgenic. The same is likely true if SHBG is over 80. We consider this diagnostic because normal lab ranges include women in menopause with almost no androgens.
- If we use transdermal androgen, what dose is necessary?
- That is much more difficult to determine, and much more dangerous because with transdermal androgen, testosterone floods the body with equal concentrations in all organs. Therefore, overdosing is much easier and too much testosterone is worse than too little. We use testosterone supplementation only in a small minority of patients who are poor converters of DHEA to testosterone. These are mostly women of African descent, based on some genetic mutations.
- What is the optimal length of dehydroepiandrosterone (DHEA) supplementation prior to IVF?
- At least 6-8 weeks and not more than 3-4 months before the IVF cycle starts.
- Do we need to dose testosterone before starting dehydroepiandrosterone (DHEA) treatment?
- You do not need testosterone if you give DHEA. To the contrary, giving both creates a risk for overdosing the patient with Testosterone.
- Can dehydroepiandrosterone (DHEA) be teratogenic? What are the effects of DHEA on the embryo?
- To our best knowledge, there are no adverse effects of DHEA on the embryo. There are also none expected as the placenta creates DHEA during pregnancy. Our studies have suggested significant improvement in egg quality, embryo quality, pregnancy rates and a significant decline in miscarriage rates after DHEA supplementation in hypo-androgenic women, the latter, likely, caused by a decline in embryo aneuploidy.
- What should we know about DHEA’s use in PCOS patients?
- You do not want to further increase androgens in PCOS patients with classical phenotype because they are already hyperandrogenic. But so-called lean – phenotype PCOS patients in most cases between ages 25-35 go from being hyperandrogenic to being hypo-androgenic and these women significantly benefit at those ages from DHEA supplementation. We have described this phenotype in medical literature in 2 manuscripts as the hypo-androgenic PCOS-like phenotype (H-PCOS) linked below.
- At our clinic, we add myo-inositol and DHEA 3 months prior to IVF. Do you do the same?
- Giving myo-inositol together with DHEA is contradictory because DHEA is given to raise testosterone, while myo-inositol does exactly the opposite. DHEA and myo-inositol, in other words, oppose each other. Myo-inositol is recommended for hyper-androgenic PCOS patients with classical phenotype; it is not to be used in women who are hypo-androgenic.
- How should we select a dehydroepiandrosterone (DHEA) brand?
- In the United States, DHEA is considered a food supplement and can, therefore, be sold without prescription over the counter. However, the U.S. literature suggests that DHEA products marketed in the country are extremely uneven in purity and overall quality. Therefore it is best to ensure that whatever DHEA you use has been independently tested at a third-party lab, and the company is willing to share that certification with you.
- We recommend a DHEA that is called Fertinatal because it:
- Mimics the DHEA our group used in initial DHEA fertility studies in source, purity and micronization
- It is designed to follow the recommended dosage schedule of 25 mg TID.
- Is 100% plant derived, pharmaceutical-grade
- Has been independently tested at a third-party lab
- We, however, in this context have to disclose a potential conflict of interest in that we receive royalties from Fertility Nutraceuticals LLC, the company that produces Fertinatal, and I own shares in the company.
For additional questions on androgen supplementation, please reach out to Dr. Gleicher directly at the Center for Human Reproduction – 212-994-4400.