Testosterone and Ovarian Reserve Study

Effects of Testosterone Supplementation on Ovarian Reserve

Testosterone and Ovarian Reserve Study: Summary

CHR is conducting a double-blinded, prospectively randomized clinical trial (RCT), in order to determine effects of testosterone supplementation in women with diminished ovarian reserve (DOR), who have not adequately raised their testosterone levels following supplementation with dehydroepiandrosterone (DHEA). The study aims to determine whether trans-dermal (applied through the skin) testosterone cream improves ovarian reserve parameters, egg and embryo quality, and pregnancy rates.

Testosterone and Ovarian Reserve Clinical Trial Overview

After years of revolutionary research on the positive effects of DHEA, a mild androgen, on ovarian reserve, CHR now routinely recommends DHEA supplementation to women of all ages with diminished ovarian reserve (DOR). After being ingested, DHEA is rapidly converted into testosterone (and to estrogen, though to a lesser degree) in the body, and in a number of research studies performed at CHR, has been demonstrated to have the following effects in women with DOR:

Effects of DHEA

  • Improves ovarian reserve parameters (AMH levels)
  • Increases the number of eggs and embryos in IVF cycles
  • Improves the quality of eggs and embryos in IVF cycles
  • Improves IVF pregnancy rates
  • Decreases aneuploidy (chromosomal abnormalities) in embryos
  • Decreases miscarriage rates

The understanding of androgen's effects on follicle maturation has in recent years undergone radical changes. While androgens were, for decades, believed to be highly detrimental to follicle maturation and egg quality, recent animal data and CHR's research on DHEA supplementation have radically changed this view. Mouse data developed by investigators at Rochester University School of Medicine (the laboratory is now in an affiliation agreement with CHR), indeed, practically indisputably, established that androgens are absolutely essential to follicle maturation during the very early stages of the process, immediately after follicles are recruited into the maturation process. Between primary follicle and small pre-antral follicle stages, granulosa cells (cells that surround the egg) carry androgen receptors. At those stages, androgens work in synergy with follicle stimulating hormone (FSH), and are absolutely essential to normal development of follicles/eggs, egg number and egg quality.

For an overview of ovarian reserve and more information about androgens' possible effects on follicular maturation, please refer to our ovarian reserve page.

A recent analysis at CHR of androgen metabolites after DHEA supplementation in women with DOR also confirmed the importance of androgens. The best results of DHEA supplementation were seen in women who started with the lowest level of testosterone and ended up with the highest after DHEA supplementation.

However, not all women can raise their testosterone levels equally after DHEA supplementation. We, therefore, decided in this clinical trial to investigate if direct testosterone supplementation of women who did not adequately raise their testosterone levels after DHEA supplementation would improve their ovarian function and increase pregnancy rates.

Frequently Asked Questions

What Is Testosterone?

Testosterone is an androgen (male hormone), present in women and men. In men, testosterone is made in the testes, while it is made in the ovaries in women. A very small amount is also produced in the adrenal glands.

How Does Testosterone Improve Ovarian Reserve?

Animal experiments, using so-called androgen receptor knock-out (ARKO) mice have unequivocally demonstrated that androgens work during the small follicle stages via androgen receptors on granulosa cells. Experiments also have shown that the same androgen receptors on oocytes do not have an equally important function.

These findings are important, because egg quantity and egg quality is determined at these early stages of follicle maturation, in contrast to much later stages of follicle maturation, where current therapeutic interventions in fertility centers, like treatment with gonadotropins, occur. These findings, of course, explain most of above noted DHEA effects, reported by CHR investigators.

How Can I Participate in Testosterone Clinical Trial?

A baseline blood test after about six weeks of DHEA supplementation, which is a part of the standard pre-cycle screening at CHR for patients on DHEA supplementation, will determine whether you are eligible for this study. To be eligible for the testosterone study, your testosterone levels (total testosterone and free testosterone) in the blood must be still low, despite six weeks of DHEA supplementation.

If you are eligible for the study, your clinical coordinator will ask you if you want to participate in the study. If you agree to participate, you will need to sign an informed consent, after which you will be randomized into either the study group, which receives testosterone, or the control group, which receives a placebo.

No Additional Cost to Participate in Testosterone Clinical Trial

There will be no additional costs to you as a participant in the testosterone study. However, you will still be responsible for the routine part of your IVF cycle costs.

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