DHEA: New Treatment for Women with Diminished Ovarian Reserve (DOR)

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DHEA supplementation is a relatively recent development for female infertility, used primarily in women with diminished ovarian reserve (DOR). Diminished ovarian reserve occurs either due to premature ovarian aging (POA) in younger women, or as a consequence of female aging. Introduced into fertility treatment by CHR in 2004, DHEA supplementation has, worldwide, demonstrated remarkable results. Many women who had been advised by other fertility centers that their only chance of conception was with egg donation, have still conceived under our care, with use of their own eggs. In those women with diminished ovarian reserve, DHEA supplementation with IVF protocols developed at CHR has, therefore, contributed to life-changing events.

Since the first CHR publication on DHEA in 2005, and following a series of publications refining the utilization of DHEA and expanding understanding of the underlying mechanisms of DHEA, DHEA supplementation has gradually gained worldwide momentum. A survey of IVF centers in 2010 found that about a third of all IVF centers in the world were already utilizing DHEA to improve pregnancy chances in women with DOR by improving quality and quantity of oocytes (eggs) and embryos.

Formally recognizing CHR's crucial role in the introduction of DHEA supplementation into female infertility treatment, the United States Patent and Trademark Office has so far issued CHR two patents (#7615544 and #8067400) related to the use of DHEA and other androgens in the treatment of female infertility.

In addition, CHR's continuous research on DHEA and fertility has led to a number of insights that may fundamentally change our understanding of ovarian reserve. The basics and the cutting-edge on this topic is available on our ovarian reserve page.

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DHEA's Beneficial Effects on Female Fertility

The investigators at CHR have successfully utilized dehydroepiandrosterone (DHEA, a mild male hormone that is converted to testosterone and estardiol in the body) for a number of years in women with diminished ovarian reserve (DOR), whether their low ovarian function is due to advanced age or premature ovarian aging (POA). In doing so, we have been able to demonstrate that in such women, DHEA supplementation has quite remarkable beneficial effects, best summarized as rejuvenating ovarian function. DHEA's effects on women with premature ovarian failure (POF), however, need more research.

Table 1: Beneficial DHEA Effects on Female Fertility
  • DHEA increases IVF pregnancy rates
  • DHEA increases the number of eggs and embryos
  • DHEA improves the quality of eggs
  • DHEA improves the quality of embryos
  • DHEA reduces aneuploidy (chromosomal abnormalities) in embryos
  • DHEA reduces the risk of miscarriages
  • DHEA shortens the time to pregnancy
  • DHEA increases spontaneous conceptions
  • DHEA improves cumulative pregnancy rates in patients under fertility treatment
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DHEA's Side Effects

During the time CHR has been working with DHEA, we have carefully monitored the side effects of DHEA, and have been impressed by how rarely even the most common side effects, such as oily skin, acne and hair loss, seem to occur.

Please contact us if you have any further questions about DHEA supplementation.

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CHR video: Diminished ovarian reserve (DOR) and DHEA


Dr. David Barad explains DHEA treatment for aging ovaries.


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DHEA for Fertility: Inspired by a Patient

The story of DHEA began not too long ago with a very important lesson, taught by one of our patients: The patient on her own started supplementation with DHEA. When her oocyte (egg) yield greatly increased in subsequent IVF cycles, we started to question what was going on. That was when she informed us of her DHEA regimen. After approximately four months of DHEA supplementation, her over 42-year-old ovaries were behaving like those of a much younger woman. Since then, we have been diligently investigating DHEA, and carefully analyzing outcomes, steadily publishing our DHEA study results and applying the new knowledge to clinical practice.

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CHR's Research on DHEA and Fertility

To chronicle our clinical research into DHEA, we present the table below, summarizing the peer-reviewed CHR publications on DHEA in the medical literature. For a complete list of CHR's scientific publications, please refer to our publications list.

CHR's Published Research on DHEA and Ovarian Reserve

Gleicher N and Barad DH, Increased oocyte production after treatment with dehydroepiandrosterone. Fertil Steril 2005;84(3):756.

This was the first case report on the effects of DHEA on oocyte production. Describing the stunning increase in oocyte production after supplementation with DHEA in a 42-year-old patient with severe DOR, the report (correctly, as it turned out,) speculated that "ovarian function may be salvaged, even in women of advanced reproductive age."

Barad DH and Gleicher N, Effects of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod 2006;21(11):2845-9.

In this case-control study, 25 patients underwent IVF cycles both before and after supplementation with DHEA. After DHEA treatment, patients had more oocytes that fertilized and more normal embryos on day-3. More embryos were transferred, and average embryo grade were significantly higher (better), confirming the earlier hypothesis that DHEA supplementation may have beneficial effects on the ovarian functions of women with DOR.

Barad DH, et al, Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian reserve. J Assist Reprod Genet 2007;24(12):629-34.

In this case-control study, 190 women with DOR were divided into DHEA-supplemented group and control group. Women who received DHEA supplementation had more than double the pregnancy rates of women without DHEA (28.4%, compared to 11.9%).

Gleicher N, et al, Miscarriage rates after dehydroepiandrosterone (DHEA) supplementation in women with diminished ovarian reserve: a case control study. Reprod Biol Endocrinol 2009;7(7):108.

A fertility center based in Toronto, Canada, participated in this study. Women on DHEA supplementation had significantly lower miscarriage rates at both centers, compared to those for the general IVF population. Both centers reported an identical miscarriage rate for DHEA-supplemented women. The improvement was more pronounced among women over 35. The miscarriage rates in women on DHEA supplementation were comparable to miscarriage rates in normal, fertile patients, despite their DOR status, suggesting that DHEA may reduce embryo aneuploidy.

Gleicher N, et al, Improvement in diminished ovarian reserve after dehydroepiandrosterone supplementation. Reprod Biomed Online 2010;21(3):440-3.

To determine whether DHEA objectively improves ovarian reserve, this study investigated the AMH levels of 120 women supplemented with DHEA prior to IVF cycles. AMH levels significantly improved after DHEA supplementation over time. Women younger than 38 saw their AMH concentrations improve more than older females.

Gleicher N, et al, Dehydroepiandrosterone (DHEA) reduces embryo aneuploidy: direct evidence from preimplantation genetic screening (PGS). Reprod Biol Endocrinol 2010;10(8):140.

In this 1:2 matched study, 22 women undergoing PGS after DHEA supplementation were compared with 44 women undergoing PGS without DHEA. DHEA significantly reduced the number and prevalence of aneuploidy (chromosomal abnormalities) in embryos, suggesting that a part of the beneficial effects of DHEA on women with DOR is exerted through reduction in aneuploidy in embryos.

Gleicher N and Barad DH, Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR). Reprod Biol Endocrinol 2011;17(9):67.

An extensive and detailed review of current best available evidence in this study confirmed that DHEA improves ovarian function, increases pregnancy chances and, by reducing aneuploidy, lowers miscarriage rates. Based on the improvement of oocyte/embryo quality after DHEA, this study introduced a new concept of ovarian aging, where ovarian environments, but not oocytes themselves, age. The study also suggested that DHEA may be the first pharmacological agent that beneficially affects aging ovarian environments.

Gleicher N, et al, The role of androgens in follicle maturation and ovulation induction: friend or foe of infertility treatment? Reprod Biol Endocrinol 2011;9(1):116.

Broadening the scope beyond human fertility and into published animal data, this extensive review of literature theorized that androgens, including DHEA, may play an essential role in the maturation of oocyte-containing follicles. At certain therapeutic concentrations, DHEA and other androgens may be capable of improving the early stages of folliculogenesis. The study presented the possibility that androgens like DHEA may be forerunners of a completely new class of ovulation-inducing medications that affect much earlier stages of follicle maturation than gonadotropins.

Weghofer A, et al, Live birth chances in women with extremely low-serum anti-Mullerian hormone levels. Hum Reprod 2011;26(7):1905-9. This study, published with Dr. Weghofer, CHR's affiliate in Austria, as lead author, showed that DHEA-supplemented women can conceive at reasonable rates even with the most severe forms of DOR, including undetectable levels of anti-Müllerian hormone (AMH). Similarly, moderate but still reasonable live birth rates were possible with DHEA supplementation.

In 2010, a first prospectively randomized trial of DHEA supplementation was conducted by a team of Israeli researchers. This study, though small in size, confirmed the beneficial effects of DHEA on diminished ovarian reserve (DOR). While still continuing an ongoing clinical trial of DHEA in women with so-called "unexplained infertility," CHR's principal focus is now on refining who benefits the most from DHEA supplementation.

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CHR Receives Two U.S. Patents on DHEA Supplementation in Female Infertility

In recognition of CHR's pioneering role in the introduction of DHEA supplementation into female fertility care, the U.S. Patent and Trademark Office (USPTO) has so far issued two patents regarding the use of DHEA in the fertility context:

Table 2: DHEA Patents Issued to CHR
Patent #7915544 Method of improving cumulative embryo score and quantity of fertilized oocytes, increasing euploidy rate and of normalizing ovarian function using an androgen such as dehydroepiandrosterone
  1. A method of increasing human female fertility through in vitro fertilization by improving quality of a human embryo as measured by an improved human embryo score, said method comprising: administering about 75 mg per day of dehydroepiandrosterone to a human female for at least or equal to four consecutive months without concurrent administration of gonadotropin, wherein said human female is a premenopausal human female with diminished ovarian reserve; harvesting a plurality of oocytes from said human female; and fertilizing said plurality of oocytes and forming at least one human embryo having an improved human embryo score, said at least one human embryo comprising a plurality of cells and cytoplasm; wherein said improved human embryo score is based on factors including uniformity of said cells, amount of fragmentation of said cells, and color and consistency of said cytoplasm.
  2. A method according to claim 1 further comprising inducing ovulation in said human female prior to said harvesting said plurality of oocytes.
  3. A method according to claim 1 wherein said at least one human embryo comprises a plurality of human embryos, and said improved human embryo score increases a cumulative embryo score, wherein said cumulative embryo score is a product of multiplying said human embryo score by said plurality of human embryos by a number of cells in each said plurality of human embryos, and further wherein said cumulative embryo score is at least or about 90.
  4. A method according to claim 1 wherein said human female is over 40 years in age.
Patent #8067400Androgen treatments in females
  1. A method of decreasing aneuploidy rates in human embryos comprising administering an androgen to a female for at least two months.
  2. A method according to claim 1, wherein said female is human.
  3. A method according to claim 1, wherein said androgen is dehydroepiandrosterone.
  4. A method according to claim 3, wherein said dehydroepiandrosterone administration comprises between 50 and 100 mg per day of said dehydroepiandrosterone.
  5. A method according to claim 3, wherein said dehydroepiandrosterone administration comprises between 15 mg and 40 mg of said dehydroepiandrosterone administered about three times a day.
  6. A method of decreasing time to pregnancy and increasing pregnancy rates in females comprising administering an androgen for at least two months.
  7. A method according to claim 1, wherein the administering step decreases miscarriage rates.
  8. A method according to claim 1, wherein said female has been diagnosed with diminished ovarian reserve.
  9. A method according to claim 1, further comprising administering microdose agonist flare to said female.
  10. A method according to claim 1, further comprising administering maximal dosage of gonadotropins to said female.
  11. A method according to claim 7, further comprising decreasing miscarriage rates by at least one-third.

If you have any questions about DHEA supplementation to improve egg quality and/or increase your pregnancy chances with IVF, please contact us.

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Unexpected Side Benefits of DHEA

We have been surprised how often we hear from our patients how much better DHEA supplementation makes them feel overall. The likely explanation for this observation is that many women with DOR demonstrate low androgens (male hormones). CHR's investigators are currently exploring this issue further. Table 2 summarizes some of the specifics.

Table 3: Positive Side Effects of DHEA
  • Improved overall feeling
  • Feeling of being physically stronger
  • Improved sex drive
  • Feeling of being mentally sharper
  • Feeling of better memory

Such claims should not surprise, as other investigators reported that DHEA appears to improve cognitive functions in women (Davis et al., Journal of Clinical Endocrinology and Metabolism 2008; 93:801-8). They specifically noted that higher endogenous DHEA levels are independently and favorably associated with executive function, concentration and working memory. It seems our patients know what they are talking about!

Contact us for more on DHEA and premature ovarian aging.

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Want to Learn More?

To learn more about DHEA and our POA program at CHR, simply complete the prematurely ovarian aging consultation form.

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Last Updated: January 15, 2013