Women with the Angelina Jolie cancer gene mutation have fewer eggs in their ovaries, claims a new study.
Researchers say women carrying the BRCA1 mutation should try to avoid delaying pregnancy until their late 30s or 40s.
Our findings suggest women carrying the BRCA1 mutation should try to avoid delaying pregnancy until their late 30s or 40s when fertility is reduced anyway because of their ageExpert
Hollywood star Angelina went public in 2013 about her double mastectomy and having both ovaries removed after finding out she carried the BRCA1 mutation, which is associated with an increased risk of breast and ovarian cancer.
On average, a woman with the mutation have a 65 per cent risk of developing breast cancer and a 39 per cent risk of ovarian cancer by the age of 70.
Now researchers have discovered a link between the BRCA1 gene mutation and lower levels of a hormone that is an indicator of the number of eggs left in a woman’s ovaries.
In the first large study looking at BRCA1 and BRCA2 genetic mutations and levels of anti-Mullerian hormone (AMH) in women who carry the mutated genes, a group of international researchers found that carrying the BRCA1 mutation was associated with AMH concentrations that were, on average, 25 per cent lower than those in non-carriers.
The effect was not seen in women with the BRCA2 mutation, according to the research published in the journal Human Reproduction.
First author Professor Kelly-Anne Phillips, of the Peter MacCallum Cancer Centre in Australia, said: “This means women in their mid-30s, who carry the BRCA1 mutation, have, on average, ovarian reserves similar to those of non-carriers who are two years older.”
Although AMH is a reliable marker of ovarian reserve, Prof Phillips said: “It’s important to remember AMH is only one indicator of a woman’s potential fertility.
“The ability to conceive and carry a baby to full term is affected by many other factors as well, including egg quality and whether the fallopian tubes are unobstructed, neither of which are measured by AMH.
“Women with low AMH levels can sometimes still have a baby and, conversely, women with high AMH levels are sometimes unable to do so.
“However, our findings suggest women carrying the BRCA1 mutation should try to avoid delaying pregnancy until their late 30s or 40s when fertility is reduced anyway because of their age.
“For women trying to conceive in their 20s, any difference in ovarian reserve between BRCA1 mutation carriers and non-carriers is unlikely to be of clinical significance.”
Women who carry the BRCA1 and BRCA2 gene mutations have a higher risk of cancers in the breast, ovaries, fallopian tubes and peritoneum.
The risk increases with age and is generally higher for those with the BRCA1 mutation than with the BRCA2 mutation.
The mutations are rare in the general population - about 0.1 per cent for BRCA1 and 0.2 per cent for BRCA2.
As mutation carriers enter their early 40s they are usually advised to have their ovaries and fallopian tubes removed to minimise their cancer risk. Many women who know they are carriers try to have their children when they are younger. However, until now, there has been little good-quality evidence about the effects of these genetic mutations on non-cancer-related conditions such as fertility.
Prof Phillips and colleagues from research centres in Scotland and Australia, analysed AMH levels from 693 women, aged between 25 and 45 who had no personal history of cancer.
A total of 172 women were carriers and 216 women non-carriers from families carrying the BRCA1 mutations, and 147 carriers and 158 non-carriers were from families with the BRCA2 mutations.
The women retained both ovaries and were not pregnant or breast-feeding at the time blood was taken from them. The researchers adjusted their results to take account of age, oral contraceptive use, body mass index (BMI) and smoking.
In addition to BRCA1 mutations carriers having 25 per cent lower AMH concentrations, on average, than non-carriers, they were also more likely to have AMH concentrations that placed them in the lowest quarter when the women were divided into four groups according to the AMH levels. This was not seen in BRCA2 mutation carriers.
The researchers say their findings also raise the hypothesis that BRCA1 mutations carriers may have a higher than average risk of chemotherapy-induced menopause.
Prof Phillips added: “The hypothesis is that if BRCA1 mutation carriers have lower ovarian reserve than their non-carrier counterparts when they start chemotherapy for cancer treatment, the carriers may be more likely to develop menopause associated with the chemotherapy.
“However, this is just a hypothesis at this stage and requires further research.”