Cancer drug has potential to affect fertility in women, study suggests

A drug used to treat patients with advanced ovarian cancer has the potential to affect a woman’s fertility, scientists have said.

Researchers in Australia who conducted the study found olaparib, which is known by the brand name Lynparza, damaged the store of immature eggs in the ovaries of mice.

The drug was approved last year by the European Medicines Agency to treat women with advanced breast cancer.

Based on their findings, published in the journal Human Reproduction, the researchers recommend fertility preservation counselling for young women who may, in future, be treated with the drug as a way to cure them of breast cancer.

They said this is because women are born with a finite number of follicles in their ovaries where eggs are stored and damage to these follicles or eggs may lead to fertility issues.

We found that olaparib significantly depleted primordial follicles by 36% compared to ovaries of mice who had not received the drug

Dr Amy Winship, a research fellow at Monash University’s Biomedicine Discovery Institute in Australia and first author on the study, said: “Fertility is very commonly overlooked in many safety tests in pre-clinical studies in animal models and also in human clinical trials for new cancer drugs.

“But we know this is an important and valid concern of young cancer patients and survivors, particularly as survival rates for many cancers are improving.

“We show for the first time that olaparib is harmful to the immature eggs stored in the ovaries that will give rise to the mature eggs required to sustain fertility and normal hormone levels.”

Olaparib works by interfering with the way cancer cells repair themselves in patients who carry a faulty version of the BRCA gene.

In 2019, the drug was approved in England through the Cancer Drugs Fund for use in women with advanced ovarian, fallopian tube or peritoneal cancer as a way to prolong the effects of initial treatment.

The researchers gave mice a single dose of chemotherapy or a placebo, followed by a daily dose of olaparib or a dummy drug for 28 days.

The team then counted the number of primordial follicles – structures that contain immature eggs – in the ovaries.

<figcaption class='imgFCap'>On the left, two healthy primordial follicles in a mouse ovary, and on the right, primordial follicle remnants lacking eggs after olaparib treatment (Human Reproduction)</figcaption>
On the left, two healthy primordial follicles in a mouse ovary, and on the right, primordial follicle remnants lacking eggs after olaparib treatment (Human Reproduction)

Dr Winship said: “We found that olaparib significantly depleted primordial follicles by 36% compared to ovaries of mice who had not received the drug.”

She said that losing primordial follicles could “ultimately lead to complete infertility and early menopause once the stockpile is gone”.

The researchers recommend using fertility preservation methods such as removing and freezing ovarian tissue, follicles or mature eggs before treatment with olaparib for breast cancer.

Professor Kelly-Anne Phillips, a medical oncologist at the Peter MacCallum Cancer Centre in Melbourne, Australia, and one of the study authors, said: “In future olaparib and similar drugs may be approved for use in young women, with the intention of curing them of the disease, and for these women fertility preservation is an important consideration.

“Therefore, it is very important to understand its effects on ovarian function and we encourage researchers to consider measuring ovarian function and fertility in future clinical trials so that we have data from humans to support or refute the findings of our study in mice.”

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