Etoposide may lead to female infertility and early menopause

Emobileclinic Health News

Perhaps, one factor that may be responsible for unexplained infertility in women is the effect of a chemotherapy drug known as etoposide. Although, the drug might have been taken when female child is still a fetus in the womb, it may have adverse effects on the developing ovaries of female fetuses.

This was the submission of researchers at University of Edinburgh currently published in the open access Journal of BMC Cancer. According to Norah Spears, the study involved mouse tissue, and it was discovered that etoposide is capable of damaging the development of the ovaries while a fetus is in the womb. This is so because the drug affects the germ cells in the ovaries responsible for the growth of eggs.
Etoposide appeared safe for women in the second and third trimesters of pregnancy, but there is limited information on the long-term effects of chemotherapy treatment on the future fertility of female fetuses exposed to chemotherapy.
Norah Spears believed that the study suggests that chemotherapy treatment have significant future effects on the babies of women who received chemotherapy treatment during pregnancy which would only become visible in adulthood. It is important to note that previous studies were limited to the immediate effect of chemotherapy drugs during pregnancy which include severe fetal abnormalities and miscarriages; no study has been made on the long term effect.
The basic units of the female reproductive system are the ovarian follicles with each containing an oocyte. The process by which oocytes become enclosed in follicles starts about 17 weeks into fetal development and is only completed in late pregnancy.
In the study, it was uncovered that when mouse ovaries were exposed to etoposide before follicular formation led to the death of most germ cells while the few remaining germ cells became unhealthy follicles. It was established that the moment oocytes were enclosed in follicles; etoposide had no significant adverse effects on them any longer.
The researchers used fetal and neonatal ovaries from mice and cultured them in the laboratory (in vitro). Thereafter, each group of six ovaries was exposed to varying doses of etoposide. The doses were considered low relative to those normally administered to patients undergoing chemotherapy.
When fetal ovaries were treated with etoposide prior to follicle formation, this resulted in dose-dependent damage. Total follicle numbers declined by 72% to 90% in response to medium and high doses of etoposide respectively. In neonatal ovaries after follicle formation, etoposide only had minor effects, even at doses higher than those used to treat fetal ovaries.
From the above results, Norah said that their work indicates that female mouse germ cells are particularly susceptible to damage by etoposide at a specific early developmental stage, immediately prior to follicle formation, and that there could be possible consequences to the fertility of females born to women who were treated with etoposide during the second trimester of their pregnancy. They were not sure whether the adverse effects of etoposide in germ cells were as a result of damages to the DNA, they were of the view that future study on this would offer a directive on this.
In conclusion, Norah held that a woman’s reproductive lifespan is determined before birth, while the ovaries are developing in the womb. The second trimester of pregnancy is particularly important as this is when female germ cells form follicles which will determine how many eggs a woman will be able to release in her lifetime. If the results they have seen in these mouse studies are found to be replicated in humans, some of that germ cell supply would be lost, which could later result in early menopause, thus reducing the woman’s fertility window.

Source

Norah Spears, et.al (2016) Etoposide damages female germ cells in the developing ovary, BMC Cancer Journal, doi:10.1186/s12885-016-2505-9