Mothers’ Age at Menopause May Predict Daughters’ Ovarian Reserve
A mother's age at menopause may predict her daughter's fertility in terms of the numbers of eggs remaining in her ovaries, according to new research
By assessing ovarian reserve with two accepted methods levels of anti-Müllerian hormone (AMH) and antral follicle count (AFC) in daughters and comparing it with the age of menopause in their mothers, researchers found that both AMH and AFC declined faster in women whose mothers had an early menopause compared to women whose mothers had a late menopause.
The number of eggs remaining in a woman's ovary is related to a reduction in her ability to conceive naturally, with both the number and quality of eggs starting to decline as she gets older.
"This is the first study to suggest that
the age-related decline of AMH and AFC
may differ between those whose mothers
entered menopause before the age of 45 years
and those whose mothers entered menopause
after the age of 55 years.
Our findings support the idea that the ovarian
reserve is influenced by hereditary factors.
However, long-term follow-up studies are required.
Conclusive evidence can only be obtained when we
have longitudinal studies that follow women who have
AMH measurements over time until menopause.
Therefore, interpretations of our data are limited
and the findings we have described may
not occur in any given individual."
Dr. Janne Bentzen
Copenhagen University Hospital, Rigshospitalet
The work is published online in Europe's leading reproductive medicine journal Human Reproduction .
Previous research has suggested that there is about 20 years between a woman's fertility starting to decline and the onset of menopause. So a woman who enters the menopause at 45 may have experienced a decline in her fertility at the age of 25.
Dr Bentzen: "Epidemiological studies have established a link between the age at menopause among mothers and daughters. In line with the suggested 20-year interval between the first decline in fertility and the menopause, we hypothesised that maternal factors may also have an impact on a woman's fertility potential in terms of ovarian reserve."
The researchers recruited 527 women working in health care at the Copenhagen University Hospital, who were aged between 20-40 years and whose mothers' age at natural menopause was known. They divided them into three categories: those whose mothers had an early menopause (younger than 45); normal maternal age at menopause (46-54 years); and late maternal age at menopause (older than 55).
Transvaginal sonography was used to count the number
of antral follicles in the women's ovaries. Follicles are
clusters of cells that contain the immature egg.
Every woman is born with about two million follicles,
but only 400 will ever mature enough to release an egg
for fertilisation during a woman's reproductive lifespan.
Levels of AMH were measured from blood samples.
Researchers also took a medical history, including
details of smoking habits in mothers and daughters,
oral contraceptive use and body mass index (BMI).
After adjusting for various factors that could affect results
(e.g. smoking, contraceptive use, age and BMI), doctors
found that average AMH levels declined by 8.6% for grandmothers who began an early menopause,
6.8% for grandmothers who began menopause at a
normal (average) age, and 4.2% a year in women
with mothers who began a late menopause.
A similar pattern was seen for AFC, with annual declines
of 5.8%, 4.7% and 3.2% in the same groups respectively.
The study also found AMH and AFC levels were lower
(27.3% for AMH and 26.8% for AFC levels) in oral
contraceptive users compared with non-users.
AFC in women whose mothers smoked while pregnant
was an average of 11% lower, but there was no
significant effect on AMH levels.
Dr. Bentzen felt the effect of oral contraceptive use was
likely to be temporary and unlikely to influence the
long-term decline in ovarian follicles. However,
she feels clinicians and women should be aware of it
when considering a woman's reproductive life span
or any fertility treatments.
Dr. Bentzen: "We believe there is a need for longitudinal, large studies in which ovarian reserve parameters are measured repeatedly in the same individual before, during and after the use of oral contraceptives. Additionally, we need to explore the impact of dose-response and duration of hormonal contraception on markers of ovarian reserve."
In their paper, the authors write: "Clearly, our data does not explain whether maternal age at menopause is a direct predictor of age at menopause of the offspring, or the chance of pregnancy. Nevertheless, from a biological point of view, it may be reasonable to assume that a low ovarian reserve may have a long-term effect that will shorten the reproductive lifespan.
We therefore assume that markers such as 'maternal age at menopause' in combination with AMH or AFC, and chronological age may represent a more complete picture when evaluating the ovarian reserve of the individual. This assumption awaits longitudinal studies before it can be put to test."
 "Maternal menopause as a predictor of anti-Mullerian hormone level and antral follicle count in daughters during reproductive age", by J.G. Bentzen, J.L. Forman, E.C. Larsen, A. Pinborg, T.H. Johannsen, L. Shmidt, L. Friis-Hansen, and A. Nyboe Andersen. Human Reproduction. doi:10.1093/humrep/des356