The first signs of aging are ineludible. The decrease of
ovarian function is an important turning point in a woman’s life. But, with
current increase in life expectancy women will be expected to live one-third of
there lives in this hormone deficient stage.
The average age at final menstruation period (FMP) is 51
years, but menopause occurs between 40-60 years. There is discrepancy between
the ability to maintain a normal ovulatory cycle and actual cessation of
fertility potential, which is largely controlled by a set of genes. These
genes carry heritable variants, modifying the wide range of ovarian and
reproductive aging seen in population based studies. But, there is a fixed interval of 10 years
between the end of fertility and the natural menopause.
In recent years we have seen an increase in age- related
infertility in women because of postponement of childbirth due to career
choices, education, control over fertility, financial concerns, late and second
marriages, and infertility. So,
researchers are looking for markers which can accurately predict the end of
fertility life span, limiting the number of women unknowingly facing age
related infertility. This prediction could also help in timely planning the
family or cryopreservation, and decreasing involuntary childlessness.
Currently, no marker has been yet identified that can
accurately predict the end of human fertility, hence the final menstrual period
is taken as a proxy variable to signify the end of fecundity. Personalized
forecast regarding the approximate age at menopause is usually predicted based
on age in relation to regularity of cycles.
According to the stages of Reproductive Aging Workshop (STRAW)
FSH is very accurate in determining the current state of reproductive aging,
but it does not predict the timing of final menstrual period (FMP). Similarly
other parameters of Ovarian reserve tests such as antimüllerian hormone (AMH)
and antral follicle count (AFC) and levels of inhibin-B lack standardized assays
limiting their incorporation and utility as clinical tools for staging
reproductive aging.
Researchers also turned towards identifying genetic markers
responsible predicting age at natural menopause, but despite identifying potential
genetic loci, no dominant alleles responsible for ovarian depletion have been
discovered to date. Mother’s age at menopause seems promising to the researchers
as it has demonstrated high degree of heritability. Pedigree analysis has shown
a dominant pattern of inheritance of natural menopause.
This systemic review was published in
February issue of
Journal Menopause, aims to evaluate data on prediction of age at natural
menopause based on antimüllerian hormone (AMH), antral follicle count (AFC),
and mother's ANM so as to use in clinical practice and future research.
The authors conducted three searches and systemic review and
included studies up to September 2014, which met the inclusion criteria.
.
Six studies were selected for AMH, out of which 5 were
prospective studies and 1 was cross sectional study. These studies had
limitations as the levels of AMH were determined by three different assays, and
different laboratories making pooling of data impossible. Furthermore, smoking
affects the levels of AMH and most of the studies did not correct for it.
For correlating the AFC and predicting age at natural
menopause 2 studies were found that met the criteria. AFC measurement was
performed on cycle days 2 to 4. It was seen that although in univariate
regression AFC showed be promising predictor, when corrected for age and
smoking the results were statistically non significant (P=0.13)
Mothers’s ANM is a promising variable in predicting ANM,
studies of mother’s ANM consistently
stated that among women who had early menopause, their mothers or daughters are
highly likely to have early menopause. Daughters of mothers with early
menopause also have low levels of AMH and low follicular count.
The studies included have many limitations as only including
women with regular cycles, dominance of studies with women of particular ethnicity, lack of
including women taking external hormones
and women with chronic illnesses,
such as malignant diseases, genetic diseases, and autoimmune diseases.
The main rationale for predicting ANM is to prevent unwanted
childlessness, knowledge of which would encourage women to start family early
or to timely cryopreserve eggs.
Knowing mother's age at menopause may be pivotal information
for the daughter. Further implications of knowing the ANM will also help in earlier
treatment of bone loss and CVDs.
This systematic literature review is the first to use variables
AMH, AFC, and mother's ANM in predicting menopause. This review has shown that
AMH and mother’s ANM are the most promising variables to be used in daily
clinical practice. The models used to predict ANM lack precision at both end of
the spectrum and provide wide intervals. A single reading is not capable of
predicting the exact age. A large cohort of women with variable age, corrected
for smoking and other chronic diseases are followed for a long time with
repeated measurements for AMH and AFC and incorporating mother ANM than
a firm conclusion can be drawn. However, all these markers need further
research and improvement before they can be applied into day to day clinical
practice. At present mother’s ANM seems to be most promising for future research.
References:
http://www.ncbi.nlm.nih.gov/pubmed/3536609
http://newsroom.ucla.edu/releases/researchers-find-a-way-to-predict-244164
