REPRODUCTIVE FACTORS AND THE RISK OF OPEN ANGLE GLAUCOMA (OAG) IN WOMEN

 

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.

https://journals.lww.com/glaucomajournal/fulltext/2023/11000/reproductive_factors_and_the_risk_of_open_angle.7.aspx

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.