In this module, we will learn the transmasculine hormone initiation and treatment strategy. The objectives for this module are for you to outline the transmasculine hormone treatment regimen and to identify the risks from that treatment regimen and mitigate those risks. The big difference between men and women from a hormone perspective is testosterone levels. Estradiol levels being used as a surrogate for estrogen levels are actually very similar between men and women. The levels in men, if you look at your normal ranges in your laboratories, might be slightly lower than for women, but not clinically different. However, testosterone levels are tenfold greater in men than they are in women. Therefore, for transmasculine individuals, the approach is to raise testosterone levels from the female range to the male range. The treatment can be lifelong. Specifically for transmasculine individuals who are adults titrating quickly to male serum testosterone levels is completely reasonable. But most start at half the typical dose given to non-transgender men. So, perhaps, 50 to 100 milligrams intramuscularly or subcutaneously both testosterone enanthate and testosterone cypionate are acceptable on a weekly basis. The starting dose then would be about 50 milligrams for transgender men. Note that while testosterone has historically been given intramuscularly, recent studies suggest that subcutaneous administration is just as effective and substantially less painful. In terms of the periodicity of injectable testosterones, we have moved over the decades from larger doses as infrequently as every four weeks now to the smaller doses that I just outlined on a weekly basis, which most men receiving testosterone will find acceptable in terms of their peaks and their troughs over the weeks. Certainly, gel preparations are fine and patches are okay if tolerated although most men find patches to be itchy. The serum range then is simply the normal serum range for men that is approximately 300 to 1,000 with slightly higher numbers anticipated if you are checking peak testosterone levels at 24 to 48 hours after injection. In terms of health concerns from testosterone, they really are quite few with the only concern that is demonstrated consistently being from lack of testosterone where there is a concern with bone loss. The only transgender-specific study done on this subject was done comparing transgender youth to non-transgender youth. If you look at this graph, on the far left, baseline Z-scores and note that they are using relative Z-scores and not absolute T-scores. The T-scores are all pretty normal for these younger individuals, and note therefore that because they are Z-scores, it's not that the levels are actually going down, it's that the individuals' levels are falling behind those of their peers. The middle bars represent where bone density goes when on extended puberty blockade, that is, with low testosterone levels if they were male. The far right-hand bar is where the youth got when they finally did receive sex steroids with the point being that there is some question about complete return to baseline from this particular study. Therefore, the big concern is hypogonadism and bone loss. On the other hand, supra-physiologic testosterone can stimulate red blood cell growth and unmask polycythemic entities. As a practical matter then, we follow testosterone to determine whether our patients are at goal and androgen sensitive indexes to the degree to which they help us here. That will include, for most, a hematocrit to ensure that that hematocrit is in a safe range. The Endocrine Society suggests that the safe range be less than 50 percent in order to provide a bit of a cushion between the hematocrit that is the result of an exogenous treatment and 55 percent, which is the level at which events are observed to occur per the hematology literature for individuals with polycythemia vera. Then, heart sensitive indexes might also be considered like lipid profile and hemoglobin A1c screening for diabetes. The other concern listed by the Endocrine Society is a fear of female cancers in female reproductive tissues exposed to testosterone. That is just a fear though at this juncture. It is important to recognize that transmasculine individuals in United States overwhelmingly have chest surgeries but do not have reproductive surgeries or genital surgeries, which means that most transmasculine individuals who are treated with testosterone continue to have their female reproductive organs, that is, uterus and ovaries. It is not observed that there is an increased cancer risk in those individuals. In fact, when some of those individuals have hysterectomies, removal of the uterus for other reasons later in life, those tissues are observed if anything to be atrophic like we see in post-menopausal women and not pre-cancerous. More research needs to be done in this area, but these observations are reassuring. Importantly though, that means that in addition to following the laboratory testing for transmasculine individuals, key surveillance also includes monitoring for potential future cancer risk. For most transmasculine individuals who have female reproductive organs in place, that will include Pap smears, checking for cervical cancer. If there is breast tissue present, there may be some monitoring required for breast cancer. Further, if there have been extended periods where the individual has been hypogonadal as part of their treatment regimen, there may be some bone monitoring required for osteoporosis. In summary, we have reviewed the transmasculine treatment regimens as well as the monitoring of patients to mitigate concerns from those regimens. I hope this module makes clear the relatively straightforward nature of transmasculine hormone therapy which can be safely monitored by informed clinicians.
