Menopause in BRCA1/2 Carriers
The clinical definition of menopause is cessation of cyclic bleeding for 1 year. Although there is marked variability in the onset of menopause, the median age continues to be 51.4 years. Lin et al examine a cellular abnormality that causes the loss of viable follicles by DNA damage in germ cells. Normally, the further action of germ cells may be quiescence, recruitment for development and ovulation, or apoptosis. Without regeneration in the ovary, the follicles are depleted, which leads to a perimenopausal state. This decline may result in infertility and irregularity.
In this carefully documented study, DNA mutations, repair genes, and BRCA1/2 are used as markers. Evidence from many studies indicates DNA repair genes increase the risk of primary ovarian insufficiency. Also, it is assumed that if oocytes are more prone to DNA damage and experience accelerated follicular depletion, this would lead to a higher incidence of infertility and early menopause. The white BRCA1/2 California women had definite spontaneous (natural) menopause onset 3 to 4 years earlier than the other women who were not carriers. Women who smoked had a much earlier onset as well. The authors suggested that the earlier menopause in women with the BRCA1/2 mutation may be because of an even narrower reproductive window, as shown in some statistics for infertility and miscarriage.
Based on these data, healthcare providers consulting these women on fertility may recommend earlier childbearing. The statistics are sound, and the results are documented and explained. Perhaps an important aspect is this study’s design using a marker system to translate the presence of a common problem in women. With increased longevity, the trend for late pregnancies must be questioned in light of these results. Gestation should be reckoned with in any case where early perimenopause is a potential medical hazard.
Commentary by Bernard A. Eskin, MS, MD
The clinical definition of menopause is cessation of cyclic bleeding for 1 year. Although there is marked variability in the onset of menopause, the median age continues to be 51.4 years. Lin et al examine a cellular abnormality that causes the loss of viable follicles by DNA damage in germ cells. Normally, the further action of germ cells may be quiescence, recruitment for development and ovulation, or apoptosis. Without regeneration in the ovary, the follicles are depleted, which leads to a perimenopausal state. This decline may result in infertility and irregularity.
In this carefully documented study, DNA mutations, repair genes, and BRCA1/2 are used as markers. Evidence from many studies indicates DNA repair genes increase the risk of primary ovarian insufficiency. Also, it is assumed that if oocytes are more prone to DNA damage and experience accelerated follicular depletion, this would lead to a higher incidence of infertility and early menopause. The white BRCA1/2 California women had definite spontaneous (natural) menopause onset 3 to 4 years earlier than the other women who were not carriers. Women who smoked had a much earlier onset as well. The authors suggested that the earlier menopause in women with the BRCA1/2 mutation may be because of an even narrower reproductive window, as shown in some statistics for infertility and miscarriage.
Based on these data, healthcare providers consulting these women on fertility may recommend earlier childbearing. The statistics are sound, and the results are documented and explained. Perhaps an important aspect is this study’s design using a marker system to translate the presence of a common problem in women. With increased longevity, the trend for late pregnancies must be questioned in light of these results. Gestation should be reckoned with in any case where early perimenopause is a potential medical hazard.
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