Reproductive factors have been found to be
important risk factors associated with a wide range of chronic diseases such as
diabetes and cardiovascular diseases. The reproductive factors such as age at
menarche and menopause are all indicators of exposure to endogenous female
hormones. There is increasing evidence of the correlation between reproductive
factors and OAG.
A meta-analysis to determine the
association between reproductive factors including age at menarche, age at
menopause, reproductive period, parity, and the risk of OAG in women was
performed by Kai and colleagues.
The ages for menarche and menopause were
defined as the ages when menstruation started and ended, and the reproductive
period was taken as the time from menarche to menopause. Meanwhile, parity was
defined as the number of deliveries.
Seven articles, which included 18,618 women,
were analyzed in this review.
The pooled results indicated that late age
at menarche (≥13 y) was significantly associated with an increased risk of OAG
(OR=1.76, 95% CI: 1.28, 2.43).
Early menopause (<45 y) also significantly
elevated the risk of OAG (OR=1.89, 95% CI: 1.23, 2.90) in categorical
meta-analyses, consistent with the inverse linear relationship between
menopausal age and the risk of OAG in dose-response analyses (P=0.002). However,
the association turned insignificant among women who experienced menopause
between the age of 45 and 49 years (OR=1.13, 95% CI: 0.76, 1.68). Neither long
nor short reproductive period was associated with the risk of OAG (<30 vs.
≥35 y: OR=1.53, 95% CI: 0.65, 3.61; 30–34 vs. ≥35 y: OR=1.67, 95% CI: 0.75,
3.70).
In addition, women who had delivered at
least 5 children were at significantly higher risk of OAG compared with those
who were nulliparous (OR=2.35, 95% CI: 1.02, 5.39), and a J-shape relationship
between parity and OAG was observed in dose-response analyses (P<0.001).
The study concluded that late menarche (≥13
y), early menopause (<45 y), and a history of 5 or more parturitions are
possible risk factors for OAG. Longitudinal studies are warranted to further
examine the relationships between reproductive factors and the risk of OAG.
Lifetime exposure to endogenous estrogen
mainly occurs in the reproductive period between menarche and menopause, and
thus some speculative theories have centered on estrogen to explain the
associations of menarche and menopause with OAG. Estrogen has been proposed to
increase the level of nitric oxide and subsequently reduce vascular resistance,
which seemed to play a role in the pathogenesis of glaucoma. The estrogen
metabolism single-nucleotide polymorphism pathway was previously found to be
associated with OAG, which signals the possible impact of genetic factors. In
addition, glaucoma is considered an optic neuropathy, while previous studies
have reported that estrogen had a protective effect on the optic nerve.
Estrogen deficiency may contribute to accelerated aging and greater
susceptibility to glaucomatous damage. Therefore, the higher risk of OAG found
in women who experienced late menarche or early menopause may be explained by a
longer absence of exposure to estrogens.
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