If you are having trouble getting pregnant and are a poor ovarian responder, you may have heard that ovarian response can be increased with testosterone during IVF.
The possibility of using testosterone supplements such as Androgel or DHEA for infertility raises many questions, including:
What types of testosterone supplements are there?
How are they taken?
Which one is most effective?
What are the side effects?
First, it's important understand the role of testosterone in IVF. Ovarian testosterone levels influence the ability of follicles to respond to fertility drugs during stimulation. Testosterone affects follicular response by increasing FSH-receptor activity and growth promoting substances in the follicles (insulin-like growth factor-1 or IGF-1). This results in an increase in the antral follicle count as well as ovarian response.
Testosterone levels decrease with age and may be correlated to a similar age-related decrease in antral follicle count (AFC) and anti-mullerian hormone (AMH) levels. This issue was discussed in an article by David Meldrum and his colleagues in a paper in the January issue of the journal Fertility and Sterility.
Does the addition of testosterone to stimulation protocols improve the outcome of IVF? The data are preliminary but the outcomes are promising. Various approaches for testosterone supplementation have been attempted. Here is what we know so far.
A 2.5 mg testosterone patch was administered for 5 days (Balasch et al., 2006) prior to stimulation. This resulted in a decrease in the incidence of poor response despite using lower doses of fertility drugs.
The use of testosterone gel (Androgel) seems to be the most promising of the lot. A dose of 12.5 mg of testosterone gel for 3 weeks prior to starting stimulation seems to have the best effect. Application of the gel to the upper arms was more effective than on the outer thighs. Androgel was more effective than the generic version of the drug. This resulted in an increase in the number of mature eggs, good quality embryos and the implantation rate.
The use of DHEA for infertility (25 mg tablet, available over the counter, dose is two or three tablets daily) for 2 – 3 months prior to starting stimulation has been proposed. This has been the most widely used treatment for the past couple of years. The data, however, is preliminary and large, properly designed studies supporting its use are needed.
These increase intraovarian testosterone by blocking the conversion of testosterone to estrogens. The commonly used drug is Letrazole and the dose is 5 mg daily for 5 days, usually started along with stimulation. The addition of Letrazole reduced the amount of fertility drugs needed for stimulation, increased the number of eggs retrieved and the implantation rate.
Addition of LH/hCG
Adding LH or hCG to the stimulation protocol is another way of increasing testosterone levels in the ovary. LH (and hCG) stimulates the theca cells to release testosterone. We have been using these routinely in our stimulation protocols. The easiest way of adding LH/hCG is by using Menopur (which has approximately 8 – 10 units of hCG per 75 units).
Growth hormone stimulates the release of IGF-1 by the liver. This in turn stimulates testosterone production in the ovary. It may increase the number of mature eggs and reduce the total dose of fertility drugs used for stimulation. Growth hormone is expensive!
Side Effects of Testosterone Treatment
So far with the use of a (relatively) low dose and short duration of use there have been no reports of increase hair growth or voice change with the use of testosterone supplements.
Dr. Karande is Board Certified in the specialty of Obstetrics and Gynecology as well as the subspecialty of Reproductive Endocrinology and Infertility. He is a Fellow of the American College of Obstetricians and Gynecologists and Member of the American Society for Reproductive Medicine.