DHEA: An anti-aging hormone with potent benefits for your fertility!

In this blog, we will describe the scientific evidences showing how DHEA holds all his promises as a great asset to improve your fertility!

1- What is DHEA?

Dehydroepiandrosterone (DHEA), secreted by the adrenal glands, is the most abundant circulating steroid hormones in humans. Its level reaches a peak between the age of 20 and 30 years old followed by a progressive decline (1) that reaches -60% at the time of menopause (2). DHEA is considered as a precursor of hormones further metabolized into potent androgens and estrogens. DHEA is also secreted in the ovary, in cells surrounding the growing follicle, namely theca cells. These cells produce androgen from the DHEA, which is then converted into estradiol in granulosa cells (cells supporting the oocyte’s development) (3).

2- DHEA can help improve your fertility!

a-Better chances for success

A 12 weeks supplementation of micronized DHEA 75 mg before a stimulation protocol for in vitro fertilization (IVF) was shown to improve the ovarian function in young poor responders (4):

A daily DHEA supplementation of 50 mg for 12 weeks (5) has also shown promising results in poor responders who experienced previous failed cycles as seen by:

Similar supplementations have been shown to increase pregnancy rate and lower miscarriage rate in patients with diminished ovarian reserve (6-9) or more generally in women with different causes of infertility including age (10-11).

b-Improvement in hormonal profiles

Many studies showed that DHEA supplementation improved hormonal profiles and could enhance the response to ovarian stimulation with:

c-Improvement of endometrial receptivity

Like ovarian aging, the endometrial receptivity may also be altered as women age. Endometrial receptivity and embryo implantation require the transformation of endometrial cells into receptive cells, a process known as decidualization that require the production of androgens among other factors (14). HOXA10 is a factor essential for the regulation of the endometrial cells development and receptivity during the window of implantation (15). Lower expression of HOXA10 was found in the endometrium of ENDO patients (16). In a study (17), poor ovarian responder patients (POR) were treated with DHEA at 75mg for at least 6 weeks and were compared to POR patients left untreated. POR women on DHEA showed an over 7-fold increase in HOXA-10 mRNA expression as compared to the untreated patients. This study strongly suggests that DHEA improves endometrial receptivity, likely by transforming into estrogen. In an in vitro study (18), endometrial cells were isolated from women of advanced reproductive age (with decreased DHEA levels). When treated with DHEA, it induces a process of cell decidualization while increasing androgen production. DHEA can enhance decidualization and endometrial receptivity as seen by increased levels of marker of endometrial receptivity (such as SPP1 or osteopontin) by acting as precursors to androgens produced within the endometrium.

d-Improvement of mitochondrial function

The maturation of an oocyte leading to ovulation is a complex process requiring the formation of the meiotic spindle and the production of energy by the mitochondria (19). Mitochondria is one of the key organelles involved in oocyte quality and necessary for the correct division of the future embryo.A previous study has shown an impairment in mitochondrial function in poor ovarian responders (20). More recently, scientists assessed the effects of DHEA on mitochondria in cumulus cells (cells surrounding the oocyte and the granulosa cells) of poor ovarian responders treated for 8 weeks or left untreated (21-22).

Results showed that DHEA supplementation was able to restore:

DHEA treatment may ameliorate IVF outcomes at least, in part, by improving mitochondrial function and reducing apoptosis in cumulus cells.

e-DHEA: anti-inflammatory and hypolipidemic actions

In a study including male and female patients treated with 50mg DHEA per day (23), results showed:

3- What mechanisms are involved in mediating DHEA benefits?

Androgen receptors (such as receptor for testosterone) are present in the granulosa cells and are key regulators of normal ovarian development and function (24-25).

A reduced androgen signaling may be responsible for:

Up to 50 % of follicular fluid testosterone during ovarian stimulation comes from circulating DHEAS (sulfated form of DHEA), thus DHEA act as a precursor for testosterone in the follicular fluid (26) and may play a key role in the development of follicle leading to ovulation. Further, DHEA increases androgen receptor (AR) and follicle stimulating hormone receptor (FSHR) expression (27) which induce a better follicle growth and responsiveness to ovarian stimulation.In addition, DHEA administration increases serum concentration of insulin-like growth factor-1 (IGF-1) (28), which has been reported to be associated with oocyte quality and embryo development (29-30) DHEA activates a factor, Peroxisome proliferator-activated receptor alpha (PPARα) (31), whose low concentration has been linked to the production of ceramides, molecules linked to the apoptosis of oocyte (32) and are toxic to the embryos (33). Thus, DHEA supplementation can restore PPARα levels and keep ceramides production under control.

You can learn more on the detrimental impact of ceramide on your fertility in this blog. Further, by binding on PPARα, DHEA triggers the mitochondrial enzymes involved in fat oxidation and represses activation of enzymes involved in fat synthesis thus lowering visceral fat and triglyceride levels (34-35).

DHEA also inhibits nuclear factor Kappa B and the production of IL-6 and TNFα (36-37).

4- DHEA supplementation: how does this work?

Prior to recommend any DHEA supplement to any of our patients, we are measuring their testosterone levels (Total and free testosterone) as well as their DHEAS levels (sulfate form). We are also routinely following these levels once our patients are on DHEA supplements.

Normal ranges for women between 20 and 45 years old are mentioned below (source: Mayo Clinic):

Besides aging women, a subset of PCOS patients can also benefit from DHEA supplementation. Indeed, a recent article (38) described a novel phenotype in lean, young (35 years old) PCOS patients (polycystic ovary syndrome) presenting high AMH but low total testosterone levels and low DHEA levels.Interestingly, high prevalence of TPO antibodies (thyroid peroxidase revealing a thyroid autoimmune issue such as Hashimoto’s thyroiditis or Grave’s disease) was also noted in these PCOS patients with low testosterone levels (38). Their decrease in adrenal androgen production is likely due to an autoimmune assault on their adrenal glands. Most strikingly, after DHEA supplementation, PCOS patients with low testosterone levels had higher number of embryos transferred than women with classical PCOS (high-testosterone patients).

At Braverman Reproductive Immunology, we are constantly working in studying the latest discoveries in the field of reproductive immunology and promoting their use to offer you better diagnostic, monitoring and treatments. We are systematically determining your testosterone and DHEA levels and if appropriate, we recommend DHEA supplementation to restore optimal levels and maximize your chances of having good oocyte and embryo quality.

Our DHEA supplement is now available for purchase online.

For more information about our supplements range, please consult our website.

Questions? Call 516.584.8710

We would be happy to help you take control of your fertility journey and answer any questions you may have.

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