The effects of sex hormones on cardiovascular disease risk factors among transgender men and women undergoing hormone therapy in Philadelphia

Michael Thomas LeVasseur

doi:10.17918/etd-7730

Cardiovascular disease (CVD) is the leading cause of death in America (1). There exists a sex disparity in cardiovascular disease such that men are twice as likely to die of CVD as women (2). This may be the result of genetic differences that put men at a higher risk of CVD than women, though studies have not found any evidence to date (3). Behavioral effects, such as diet, exercise, and smoking, have shed some light into this sex disparity, but do not fully explain the effect (3). It has been postulated that hormones play an important role in cardiovascular disease. Specifically, a prevailing theory postulates a cardioprotective effect of estrogen, though clinical trials exploring this have not shown any protective effect of estrogen on cardiovascular health among postmenopausal women (4-12). An alternative hypothesis has suggested a detrimental effect of testosterone, although fewer studies have investigated the effects of testosterone on cardiovascular disease (3). Research into this field has almost exclusively focused on the estrogen-protection hypothesis (3). Transgender men and women provide a novel population to study the effects of hormones on cardiovascular risk. Patients undergoing hormone therapy receive supraphysiologic doses of hormones to inhibit endogenous sex hormones and replace these with levels of hormones of the desired sex (13). Studies exploring the effects of hormone therapy in this population are few (14) and have significant limitations including small sample sizes and short follow-up times (15). Although guidelines for the care of the transgender population have been put forth by the Endocrinology Society (13), these guidelines are based on limited studies, and information on the long-term effects of hormone therapy are unknown (16). Echoing the limitations of these guidelines and recognizing the gaps in research, the Institute of Medicine has strongly recommended increasing research into the health of this population (14). In Philadelphia, the Mazzoni Center provides targeted health services to the lesbian, gay, bisexual, and transgender (LGBT) population. Services provided by the Mazonni Center to transgender men and women include counseling, hormone therapy, and regular medical care. In 2010 alone, the Mazzoni Center served 18,117 patients through direct services, 14%, of which, were transgender (17). To explore the relationships between hormone therapy and blood pressure, a sample of 441 transgender women and 391 transgender men were matched to cisgender men and women from a clinic population. To explore the relationships between hormone therapy and lipids, a sample of 144 transgender women, 171 transgender men, and 440 cisgender men were selected from a clinic sample. Patients were followed up for a minimum of 1.5 years over 3 patient visits. We assessed the changes in systolic blood pressure, diastolic blood pressure, HDL and LDL cholesterol using generalized linear modeling among transgender patients alone as well as a cisgender referent analysis. We also assessed whether or not BMI mediated the relationships explored above. We first assessed whether changes in BMI were associated with hormone therapy over time as well as the longitudinal association of BMI with systolic and diastolic blood pressure, HDL, and LDL cholesterol levels. Autoregressive mediation analysis was used to determine the mediating effect of changes in BMI on the influence of hormone therapy on measures of cardiovascular disease risk. Despite a slight decrease in systolic blood pressure among transgender women, we found no clinical differences in blood pressure over time. Compared to cisgender patients, transgender women have blood pressure levels that are similar to cisgender men and transgender men have blood pressure levels that are similar to cisgender women. Over time, transgender women have a decrease in blood pressure while transgender men have an increase in blood pressure over time. We conclude that the effects of hormone therapy on blood pressure is minimal among transgender patients. Transgender women had an increase in HDL cholesterol, a decrease in LDL cholesterol after 1.5 years of hormone therapy. Transgender men had a decrease in HDL cholesterol and an increase in LDL cholesterol over the same time period. Although transgender women had similar HDL levels to cisgender males at baseline, by 6 months of follow up, these levels were statistically distinct from cisgender men. Conversely, transgender men were quite different in HDL cholesterol at baseline compared to cisgender men and became statistically similar at 6 months of follow up. There were no differences in LDL cholesterol comparing transgender men to cisgender men at any point during follow up. We conclude that hormone therapy increases the CVD cholesterol risk profile among transgender men, but decreases the CVD cholesterol risk profile among transgender women. Transgender women had a slight increase in BMI over 18 months of hormone therapy and transgender men had a slight increase in BMI after 6 months of hormone therapy, an effect that did not persist after 18 months of follow up. These changes over time did not have a significant effect on blood pressure or lipids measurements. We concluded that BMI does not change significantly over the duration of hormone therapy and does not mediate the effects of any of the factors explored.

The effects of sex hormones on cardiovascular disease risk factors among transgender men and women undergoing hormone therapy in Philadelphia

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The effects of sex hormones on cardiovascular disease risk factors among transgender men and women undergoing hormone therapy in Philadelphia

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