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Yemi Adesanya-Famuyiwa, MD
Genetics and Reproductive Lifespan
Montgomery Fertility Center
. http://montgomeryfertilitycenter.com/

Genetics and Reproductive Lifespan

Genetics and Reproductive Lifespan

The reproductive life span and women has been shown to be intimately associated with some genetic factors. The reproductive life span in women is defined as the time span from the onset of puberty until the onset of menopause when the compliment of oocytes [eggs] is depleted and all menstrual cycles stops.

There are several genetic factors contributing to variation in traits and diseases influencing female fertility. Due to recent genetic advances, scientists are now able to reveal shared biological pathways linking puberty timing, fertility, reproductive aging, and health outcomes. This genetic difference can result from mutations in specific genes, as well as and variation at many sites within the human genome.

The onset of menstruation occurs with maturation of the reproductive endocrine system and results in the onset of menstrual cycles and sexual maturity for women. It occurs between the ages of 9-14. It has long been observed that the age at which girls start menstruating has been declining in several countries. There is no evidence that this is linked to genetic mutation. Early menstruation is associated with early initiation of sexual activity, early pregnancy, high risk of sexually transmitted infections, increased risk for obesity, increased risk for type 2 diabetes, increased risk of breast cancer, and metabolic syndrome.

The timing of puberty between individuals is a highly poly-genetic trait with both rare and common variants contributing to the variation in age of menarche. They are rare mutations in genes that disrupt the development of function of the sex hormone releasing pathway from the brain, the pituitary hormones, and air receptors as well. Some of these mutations can result in absence of puberty. Other mutations are implicated in the less severe delayed onset of puberty and may contribute to population variability and age of menstruation. Genome wide population studies in healthy women in Europe and non-European populations of identified key genetic factors regulating puberty timing. In Japanese women, the mean age of menstruation was 13.9 years but there is a decreasing trend to a mean age of 12.3 years for women and newborn after 1965. Genomic studies have revealed 10 significant signals associated with early age of menstruation in Japanese women in addition to two normal regions not previously reported any appearing women and one novel Japanese specific signal.

With earlier age of onset of menstruation there is an association with higher risks for uterine fibroids, endometriosis, and earlier natural menopause. Menopause typically occurs between the ages of 40-60 with an average of 51 using western countries.

 The age of menopause has a strong genetic component with more than 50% variation due to genetic factors. Recent results of genome wide studies have implicated mutations in genes that are responsible for repair of DNA damage. Mutation of such genes is also associated with increased risk of cancer. The most widely known of these include mutation of the BRCA1 gene. Later age at menopause is associated with increased risks for breast, ovarian and endometrial cancer. Many of the genetic markers influencing menopause are related to DNA damage repair genes. In addition, later age at menopause results in longer exposes to high levels of estrogen for women thereby increasing the risk of estrogen receptor positive breast cancer.

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