Study Finds Risks of Damage to the Ovaries from Chemotherapy For Hodgkin’s Lymphoma in Women 35 and Older
It is well known that chemotherapy drugs work by warding off cancer cells or stopping them from multiplying. However, they can also affect some of the healthy cells within the body.
It is well known that chemotherapy drugs work by warding off cancer cells or stopping them from multiplying. However, they can also affect some of the healthy cells within the body. This, in turn, can cause unwanted side effects, such as reduced fertility. The likeliness of one’s fertility being affected depends on several different factors. This includes the chemotherapy drugs that are being used, as well as the dosage that is being used. Although it is not possible to predict chemotherapy will affect one’s body, some of the chemotherapy drugs have a larger impact than others, in particular when they are given at a higher dose and over an extended period of time.
According to a recent study, standard chemotherapy used to treat Hodgkin’s lymphoma in women of premenopausal age, as well as BEACOPP chemotherapy used in those at any age, risks damage to the ovaries. More specifically, chemotherapy induced ovarian function is of great concern among women age 35 or older who are diagnosed with Hodgkin’s lymphoma.
The study – “Determinants of ovarian function after response-adapted therapy in patients with advanced Hodgkin’s lymphoma (RATHL): a secondary analysis of a randomized phase 3 trial” – was published in the journal The Lancet Oncology.
Participants and methods
The current method used to treat Hodgkin’s lymphoma is an ABVD chemotherapy regimen - adriamycin, vinblastine, bleomycin, and dacarbazine. This treatment is connected to less ovarian damage, in comparison to previous treatments.
For patients that are at a higher risk of relapse or with advanced diseases, some doctors recommend BEACOPP chemotherapy, which involves a combination of etoposide, bleomycin, adriamycin, oncovin, cyclophosphamide, prednisolone, and procarbazine. This treatment is tied to a higher percentage of toxicity in the ovaries.
Researchers in Edinburg and London decided to analyze the effect of various chemotherapy regimens - including ABVD or AVD and escalated dose of BEACOPP (which is given over the course of every 3 weeks) or time intensive BEACOPP-14 (administered every 2 weeks) - on the function of the ovaries in women who have Hodgkin’s lymphoma. They enrolled women who at the time of their diagnosis were under 45 for the study and set them with participants of the randomized RATHL Phase 3 trial, to direct response adapted chemotherapy in women with advanced Hodgkin’s lymphoma.
The ovarian function of each woman was monitored during, and 3 years following chemotherapy through the levels of antimüllerian and follicle-stimulating hormones in the bloodstream. Antimüllerian hormone is a hormone that is secreted by cells in developing egg sacs and it is used to calculate remaining egg supply. Follicle-stimulating hormone is a hormone produced by the pituitary gland and it is used to regulate the function of the ovaries. It also responds to the production of the two main female hormones, which are estrogen and progesterone.
Hormonal profiles during and after treatment
Out of 67 women assessed for the antimüllerian hormone, 24 were treated with ABVD, 33 were treated with AVD, 6 were treated with escalated BEACOPP, and 4 were treated with BEACOPP-14. The researchers found that the levels of the antimüllerian hormone were vastly reduced during all of the chemotherapy regimens. Following one year of treatment, the levels of the antimüllerian hormone in the women treated with ABVD and AVD returned to normal, while the women treated with BEACOPP showed a slow and poor recovery.
The researchers also found that recovery after ABVD and AVD chemotherapy regimen was dependent on age. The women diagnosed with Hodgkin’s lymphoma before the age of 35 managed a complete recovery, while the women diagnosed with Hodgkin’s lymphoma after the 35 showed an incomplete recovery.
In regards to short term fertility, levels of the antimüllerian hormone were not a good predictor. Out of the women who were pregnant, some had very low levels, indicating that there remains an unmet need for an effective predictor of infertility among cancer survivors.
Out of 321 women assessed for the follicle-stimulating hormone, 142 were treated with ABVD, 140 were treated with AVD, 20 were treated with escalated BEACOPP, and 19 were treated with BEACOPP-14. Here, the researchers found that the levels of the follicle-stimulating hormone showed similar, but reversed trends. They found that the levels of the follicle-stimulating hormone were vastly increased during all of the chemotherapy regimens. Following one year of treatment, the levels of the follicle-stimulating hormone in the women treated with ABVD and AVD returned to normal, while the women treated with BEACOPP showed a poor recovery. This recovery was also shown to be lower in women who are over the age of 35.
According to the researchers, these findings signify the importance of addressing various types of chemotherapy regimens among women age 35 or older, as well as identifying the proper candidates for the BEACOPP regimen – regardless of their age. However, they stressed that further research is necessary before deriving to any confirmative results.
Preserving fertility
Currently, there aren’t any methods to prevent the damage that is brought on from chemotherapy on the ovaries. There are, however, ways for a woman to preserve her fertility if she has lost all of her eggs due to lymphoma treatment or if she has difficulty conceiving after treatment for lymphoma because of the low egg count.
The most common and effective option is egg freezing, which is also referred to as mature oocyte cryopreservation. Egg freezing is a method in which a woman’s eggs are taken from her ovaries, frozen while they are unfertilized, and then stored to be used at a later time. A frozen egg will then be ‘defrosted’ and combined in a laboratory with the sperm, and ultimately implanted into a woman’s uterus (this process is known as in vitro fertilization).
The entire process - beginning with the first hormone injection to having the eggs frozen - takes around 2 weeks. For women who are under the age of 35 and considering egg freezing, their chance of achieving pregnancy from a single cycle is approximately 1 in 3. For women who are over the age of 40, it is rare to turn to freezing eggs, because the chance of getting pregnant is smaller. Nevertheless, all women are provided the opportunity to discuss their fertility and preservation options with a specialist before and after cancer treatment so that their needs can be met.
References:
https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(18)30500-X.pdf
https://lymphoma-action.org.uk/about-lymphoma-side-effects-treatment/reduced-fertility
