A systematic review recently published in BMC Ophthalmology investigated the impact of female sex hormones and associated milestones of menarche (the beginning of menstruation), pregnancy, and menopause on the physiology of the cornea.
Give me some background first.
Sex hormones play a key role in the development and function of the cornea because it is a gender-dependent and hormone-responsive tissue.
The cornea expresses sex hormone receptors in at least three of the five corneal layers:
- Corneal epithelium
Talk about the study.
Using multiple databases, the literature review included a total of 55 articles.
The primary outcomes of female sex hormone-dependent changes to the cornea included:
- Central cornea thickness (CCT)
- Intraocular pressure (IOP)
- Tear break-up time (TBUT)
- Schirmer’s test
Further, Ocular Surface Disease Index (OSDI) scores were included to record symptom analyses for this review.
How do menarche and menstruation affect the cornea?
One study found that IOP increased at ovulation compared to the end of the menstrual cycle, with a difference of around 1 mmHg (p=0.05).
Another study demonstrated that the CCT tends to be thinnest (542 μm) at the start of the menstrual cycle and thickest (559 μm) at mid-cycle—during ovulation.
What about the tear film?
Numerous studies have indicated that changes in dry eye symptoms may be linked with variation in sex hormone levels during the menstrual cycle, and were found to worsen during periods of peak estrogen levels.
Then, how does pregnancy affect the cornea?
Several studies have indicated increased ocular discomfort and decreased tear production in pregnant patients.
Efe et al. found a synchronous relationship between IOP and CCT changes through all trimesters of pregnancy.
They noted a 3.1% increase in CCT in correspondence to a 9.5% decrease in IOP (p<0.001), with the highest values in the first trimester and the lowest in the third (13.8 mmHg vs. 12.4mmHg, p<0.001).
Tell me more.
A widely proposed explanation for the decrease in IOP observed during pregnancy is that female sex hormones cause an increase in aqueous humor outflow capacity.
Peak levels of progesterone, estrogen, and relaxin at the end of pregnancy correlate inversely with IOP due to the dilatory effects of progesterone and estrogen.
Lastly, how does menopause impact the cornea?
Generally, studies have shown that IOP tends to increase after menopause while CCT decreases.
One hypothesis is that the reduction in estrogen hinders the function of the carbonic anhydrase pump on the corneal endothelium, contributing to steepening of the horizontal curvature in postmenopausal patients.
Similarly, a separate study posited that the decrease in estrogen causes a lower production and release of nitric oxide from the corneal endothelium, leading to decreased CCT.
And the ocular surface?
The study authors noted that multiple studies have suggested that inflammation of the lacrimal gland, decreased meibomian gland tissue, and lower lipid production secondary to androgen deficiency could cause higher rates of DED in postmenopausal patients.
Can these findings translate to treatments?
Based on the impact of female sex hormones on the cornea, multiple study authors have speculated that these molecules could be used as potential therapeutic interventions.
Wei et al. hypothesized that estrogen could be used to protect retinal ganglion cells (RGCs)—due to its activation of collagen synthesis—to decrease the rigidity of the cornea and enhance compliance of the lamina cribrosa.
Understanding the relationship between the structure and function of the cornea and hormonal changes could be crucial signals for clinical decision-making in female patients with corneal diseases.
However, future studies are warranted to better understand the effects of sex hormones on the physiology of the cornea to develop targeted therapies.