This study aims to evaluate metabolic and hormonal parameters of individuals who are diagnosed with transmen gender dysphoria by psychiatry and referred to our outpatient clinic before cross-sex hormone therapy and compare to natal women's parameters.
Prior literature shows us hyperandrogenism is seen in transmen individuals often and it's thought to be related to PCOS. A retrospective and descriptive study designed by Becerra-Fernandez et al. showed increased hyperandrogenism and PCOS rates in transmen (6). In this study, cases that have free testosterone levels higher than 0.028 nmol/L are accepted as hyperandrogenemia. 49,4% of 77 participants were found hyperandrogenic (n = 38) and 36.6% were diagnosed with PCOS according to Rotterdam criteria (n = 28). Additionally, they have reported this higher LH levels found in the hyperandrogenemia group may be because of increased androgen secretion from ovaries. The lack of a control group was added as a limitation of the study.
Another study (Mueller et al. in 2008), which compared 61 FtoM individuals to 94 cis women has reported free testosterone levels higher than 0.028 nmol/L in the case group, hyperandrogenemia rate was 44,3% (n = 27) significantly higher than control group whose rate was 20,2% (n = 19). On the other hand, PCOS rates were in case group 14.8% (n = 9) and in control groups 12.8% (n = 12) (p values: 0,002; 0,909). Even though they included FtoM individuals before the onset of their hormone therapy, they added self-medication wasn’t questioned and this may be the reason for underlying hyperandrogenemia and this may be the limitation of their study (7).
In our study, androgen levels such as total testosterone, FAI, androstenedione, DHEAS were found significantly higher in the transmen group and muscle strength was directly correlated with these androgen levels. These findings continued in the second analysis that is done after the exclusion of PCOS patients. This hyperandrogenic status of transmen individuals who don't have a history of cross-sex hormone therapy may indicate another underlying cause of hyperandrogenemia. This study has the largest number of cases among case-control studies about gender dysphoria in current literature and it proves that transmen still have significant hyperandrogenemia after exclusion of PCOS and other causes. Our study confirms the previous studies and it is more powerful in terms of study method.
In our study, muscle strength was found significantly higher compared to the control group. In a case-control study designed by Kogure et al. including 40 PCOS and 40 healthy women, total testosterone (p < 0.01) and FAI (p < 0.01) levels were found higher in the PCOS group likewise isometric handgrip stress test results were significantly higher too (p = 0.03)(8). Another study designed in Taiwan evaluated the relationship between muscle strength in people older than 50 years and showed that FAI and testosterone are correlated with muscle strength. Despite lower testosterone levels in women compared to men, muscle strength and testosterone correlation were similar between the two genders (9). In our study findings, we showed a positive correlation between muscle strength, total testosterone (r = 0.305, p = 0.002) and FAI (r = 0.456, p = 0.000). Higher muscle strength in the case group was thought to be due to hyperandrogenemia in this group. Since there is no prior case-control study that compares transmen's muscle strength to a control group, our study is the first study in this field.
We found IGF-1 levels significantly higher in the case group in our all group analysis and PCOS patients excluded analysis (p values 0.045; 0.024). Total testosterone was also found to be correlated with IGF-1 levels (p = 0.002). Francomano et al. designed a study with 20 men diagnosed with hypogonadism and metabolic syndrome. Testosterone undecanoate was started once in 12 weeks for 60 weeks’ period and IGF-1 levels were compared with the control group. As there were no significant differences between the two groups’ IGF-1 levels at the start, by the end of 60 weeks period IGF-1 levels were found significantly higher in the testosterone group (p = 0.01) (10). In our study total testosterone and IGF-1 levels’ correlation coefficient was 0.334 which indicates a strong correlation. Likewise, FAI and IGF-1 levels were correlated and the coefficient was 0.402 (p = 0.000). Since there is no prior study that evaluates IGF-1 levels in transmen individuals our study shows a new aspect in this field. More studies are needed to be done in this area.
In terms of metabolic parameters, all group analyses showed higher triglyceride, HOMA-IR, and lower HDL levels in the FtoM group. AUC (insulin) was also higher in this group but not statistically significant. After PCOS cases were excluded, the analysis showed the same metabolic parameters before. Although the BMI values of the control group were higher after PCOS cases were excluded, dyslipidemia (high triglyceride, low HDL) and higher HOMA-IR numbers continued in the case group. In addition, AUC-insulin was significantly higher in the case group which was not before. This was interpreted as a finding supporting that insulin resistance was significantly higher in the case group compared to the control group. The presence of these metabolic syndrome-like findings in the case group can be explained by the high androgen levels in this group. In previous studies, it has been shown that metabolic syndrome parameters are significantly increased in women with high androgen levels.
In a meta-analysis that evaluates the effect of hyperandrogenism in polycystic ovary syndrome on metabolic parameters, 32 observational studies were included comprising 9556 females with PCOS. Incidences of metabolic syndrome, HOMA-IR value, the incidence of IR were significantly higher in the PCOS/HA group compared with the PCOS/NHA group and the HDL value in the PCOS/HA group was smaller than that in the PCOS/NHA group, while TC, TG, and LDL were not significantly different between the PCOS/HA and PCOS/NHA groups. Lack of case-control studies was added as a limitation of this study(11). In another study investigates whether biochemical hyperandrogenism, represented by elevated serum free testosterone, resulted in an aberrant circulating microRNA (miRNAs) expression profile and whether miRNAs can identify those PCOS women with metabolic syndrome, 42 PCOS and 20 healthy women were included. Although there were no significant differences between the two groups' age, height, weight, BMI, and waist-to-hip ratios, F-G score, total testosterone, and androstenedione levels were significantly higher in the PCOS group. PCOS group was divided into two groups according to whether they are hyperandrogenic or not. Fasting serum insulin, HOMA-IR, triglyceride levels, and metabolic syndrome incidence were significantly higher and HDL levels were significantly lower in the hyperandrogenic group(12).
In conclusion, this is the first case-controlled study that compared anthropometric, metabolic, and endocrinological parameters of transmen individuals with cis women. Various studies had shown significant hyperandrogenemia in FtoM individuals before. In our study, we showed that even when PCOS patients were excluded, hyperandrogenic status continues in these individuals compared to cis women. Since there was no significant difference between the groups according to age, BMI or weight, these findings did not seem to be due to obesity or other metabolic situations. It is clear that transmen individuals have higher androgen levels which may have been the reason for increased muscle strength, insulin resistance, and dyslipidemia compared to natal women. But the main reason for hyperandrogenism in drug-naïve transmen individuals is still not known and more comprehensive further studies are needed.