In this study, the effects of testosterone on IOP, MT, RNLF, GCC, and ocular blood flow in FMT persons were compared with healthy women and men. In our study, we found that the use of testosterone increased IOP, MT, RNFL, and GCC thickness in transgender male individuals having female genetics. In addition, we found that the serum level of testosterone was positively correlated with Peri Inf thickness in macula and S/D ratio in OA in FMT.
In our study, no difference was found between men and women in terms of IOP values. The highest IOP was found in FMT individuals using testosterone, and this was statistically significant when compared with men. The effect of hormones, especially estrogen, on IOP has been shown in many studies [7, 22]. It has been stated that despite the effect of estrogen's lowering IOP, high testosterone levels can increase IOP and increase the risk of glaucoma [23, 24]. Evidence that testosterone increases IOP has also been reported in patients with PCOS [18]. These studies are consistent with our work. In addition to studies reporting lower IOP in women compared to men, there are also studies stating that gender is not effective [25, 26]. In our study, the mean IOP of women was found to be higher than men, but this difference was not statistically significant. Endogenous high testosterone may not have the same effects as exogenous testosterone [27]. However, this situation may explain the statistical significance between FMTs, which are genetically females, and males, and can be interpreted as exogenous testosterone IOP in the female sex.
Although we found lower mean IOP in men in our study, we found that the cup/disc (C/D)ratio of men were significantly higher than FMT and women. In the literature, there are studies stating that the C/D ratio is higher in men than in women [28]. A positive correlation between disk size and the C/D ratio has been reported [29]. However, fundus photography of the cases was not performed in our study and this may be a limiting point.
In our study, the foveal thickness was greatest in the male gender. Many studies in the literature also support this finding [30]. However, the striking point is that the mean of MT measurements in FMT was significantly increased in the Para Inf, Para Sup, Peri Nas, and Peri Inf area compared to women. In addition, the mean of MT measurements in FMT has significantly increased in the Peri Inf area compared to men and it was correlated with serum testosterone levels. In a study conducted in patients with PCOS, it was stated that testosterone increased MT, but this increase may be caused by metabolic syndrome accompanying PCOS leading to Muller cell defect and macular edema [31].
Inner and outer layer thickness measurements of the macula were made to determine which layer was affected by the testosterone. There were statistically significant differences between the groups in terms of IRL and ORN. Foveal measurement in 1mm area with FD-OCT device covers 0.35 mm foveola area due to retinal anatomy and this area consists of rod and cone cells. Although there was no difference in the ORL between men and women in the fovea region, the IRL was significantly higher in men than women. However, this difference was not present in the perifoveal area. In FTM, there was a significant increase in ORL in the foveal area compared to women. For these reasons, we think that testosterone may have a trophic effect on rod and cone cells. At the same time, the increase in MT especially in the para and perifoveal area and in the IRL of the macula in FMT cases suggests that testosterone may also be effective in the inner nuclear layer with an increase in the GCC layer.
Another important point of our study is the positive effects of testosterone on RNLF and GCC layers. In FMT, Inf RNLF was significantly higher than women and men. We found that the means of Avg GCC and Sup GCC were significantly higher in FMT than in women. The neuroprotective effect of testosterone on the nervous system has been demonstrated by regeneration and improvement in neurons and glia [19, 20]. Besides, increased RNLF thickness has been reported in studies conducted with patients with PCOS. It is stated that this trophic effect is partly due to androgen and partly to nerve growth factor (NGF) detected in cases with PCOS [17, 18, 31]. Our patients had normal ovarian size and appearance and did not show PCOS findings. Therefore, we think that the increase in thickness in RNLF and GCC is due to the trophic and neuroprotective effects of testosterone.
In our study, we did not observe any difference in ocular blood flow between the three groups in CRA, OA and posterior CA. However, in correlation test, S/D ratio in OA was positively correlated with the serum levels of testosterone in FMT. There are limited studies on the effects of hormones on ocular hemodynamics and gender differences. A study investigating retrobulbar blood flow in men and women under 40 years of age indicated that ocular blood flow velocity was higher in the OA and lower in the short posterior CA in men compared to women [32]. Studies on ocular blood flow and hormones mostly focused on estrogen. Many studies have reported that estrogen decreases vascular resistance in the retinal vessel and OA and increases flow velocity [7, 9]. However, while testosterone increases RI in the central retinal artery and ophthalmic artery, it decreases the flow velocity in the central retinal artery. Testosterone works as an antagonist despite the positive effect of estrogen [13]. In another study conducted on patients with PCOS, it was reported that androgens increased ocular blood flow however they increased vascular resistance only in the OA[33]. In our study, there was no difference between the groups in CRA, OA and CA parameters. However, the absence of our patients in surgical menopause may have hidden the effects of testosterone on vessels. In addition, Doppler blood flow studies have some limitations. Doppler results depend on the experience of the ultrasonographer, which makes it difficult to generalize and standardize the results. Nevertheless, as studies on hormones and ocular blood flow increase, our knowledge on this subject will increase.
According to the Androgen Exess Society (AES), hyperandrogenism is indispensable in the diagnosis of PCOS. Clinical or laboratory hyperandrogenism occurs in PCOS. However, the dose of testosterone taken in FMT cases is a supraphysiological dose. Therefore the, FMT group creates valuable data to understand the effects of testosterone on the eye. As far as we can find from the literature, ours is the first study investigating the ocular findings of FMT individuals. The strengths of this study are its prospective nature, the examination of multiple parameters, and compliance with exclusion criteria in selecting control groups. The major limitation of the study was small sample size.
In conclusion, in our study comparing FMT individuals with normal controls, we found that testosterone caused an increase in IOP and an increase in the macula, RNLF, and GCC thicknesses. The effects of testosterone on macular thickness increase were prominent in the inner layer. In addition, serum testosterone level was positively correlated with S/D ratio in the OA. In the light of these findings, we conclude that testosterone has trophic and neuroprotective effects and also has effects on ocular blood flow.