Do Fertility Drugs Increase the Risk for Ovarian Cancer?

When couples are desirous of a pregnancy and just can’t seem to conceive on their own they are willing to try everything. I know… I ran a fertility clinic in Tel Aviv decades ago. At that time, we offered therapies for women who had ovulatory problems, blocked tubes, and men with low sperm counts. When we found no obvious problem with either the woman or the man and they could not conceive after trying for a year, we would arbitrarily use fertility therapies and combine them with insemination. Clomiphene was the first drug of choice. This anti-estrogen pill is prescribed in the beginning of the cycle (usually the 5th day after the period starts). It “fools” the pituitary gland into “thinking” that there is no estrogen on board. So the pituitary works harder and spurts out the hormone FSH (follicle stimulating hormone) which then induces the follicles in the ovary to develop and eventually (after the medication is stopped) produce an egg which can undergo fertilization. This medication is still used as first line therapy in many infertile or non-ovulating women.

If the clomiphene didn’t work, we would start  injections of hormones that “replaced” or caused the secretion of FSH and LH (luteinizing hormone) The latter, given in the form of HCG (sorry about all these initials, the latter stands for human chorionic gonadotropin) signals the follicle, and orders it to release the egg. With current IVF (I’m not sure you need this, but it stands for in vitro fertilization) therapies, we use many of these same medications.

Obviously there have been concerns about use of these therapies. The most immediate: failure to achieve pregnancy, multiple pregnancies and resultant early pregnancy loss, prematurity and pregnancy complications. Reproductive experts have (and should) inform prospective patients about all of these risks. But what about risks that could affect a woman’s health or her longevity?

Incessant ovulation increases the risk of ovarian cancer…Perhaps it’s the constant “bruising” of the ovaries’ surface as the follicle bursts and the egg is extruded. Perhaps the ongoing hormonal changes and/or induction of those changes by FSH and LH cause cellular mutations that can result in cancer. We do know that full term pregnancies and use of birth control pills (both of which stop ovulation for 9 months or years) are protective and decrease ovarian cancer risk. We also have statistics that show that women who were never pregnant are at a higher risk for this malignancy.

But what about the risk to women who take ovulatory stimulating medications in order to conceive…will the drugs put them at risk for ovarian cancer? A recent and very large study of treated women with follow-up for 35 years found that there was “no convincing association between use of fertility drugs and risk of ovarian cancer”. The study was carried out in Denmark where patient records on treatment and disease are stellar. Data from over 54,000 women with infertility who were referred to all the Danish clinics for 35 years between 1963 and 1998 was assessed. They reported that the risk for ovarian cancer was not significantly affected by use of clomiphen, human chorionic gonadotropins ( HCG), gonadotropins (LH and FSH) and gonadotropin releasing hormone. Nor did this change when they calculated the number of cycles, duration of drug use or the pregnancies of the women in the study!

So can we rest on our fertility drug laurels? Almost…when the authors looked at a very particular subtype of ovarian cancer called serous ovarian cancer they found that clomiphene users did have a 67% increase of this type of cancer when compared to women who had not taken this drug, especially after 15 or more years. The actual number of these cases found was small and hence even if the stat 67% sounds ominous, it’s an increase of a very, very slight incidence and remains rare. It may even be an artifact.

Remaining infertile is in itself a risk for ovarian cancer. The use of fertility medication and the advances in reproductive assisted technologies have reversed a condition that can cause unremitting anguish and health-compromising depression for hundreds of thousands of couples.

I consider this published report to be one that allows me to reassure my patients that ovarian cancer risk is miniscule or non existent….for those who have used fertility medications in the past and women who will now begin a quest to overcome their infertility.