In our last episode, Robin had entered the Bat Cave unannounced and unwittingly walked in while Batman was giving himself his bi-weekly injection of testosterone cypionate. Robin stopped dead in his tracks and stood staring. Batman glanced up and, without a word, turned his attention back to his injection.
As Batman silently pushed the thick liquid into his muscular thigh, Robin could stand it no more. His fists clenched, his brow furrowed, he blurted out, “Holy gender conundrum Batman!! You are so binary!!” Batman plucked the needle from his leg, dropped it into the sharps container and replied, unfazed, “Take it easy, Boi Wonder. We each have our own process. And hand me the pump, will ya? I got a date tonight.”
Well, okay, so that wasn’t really our last episode. What we were really talking about was the different types of estrogen blockers. Not nearly as much fun as Batman and Robin, but maybe more interesting. (Or not.)
As a quick review, there are three main types of estrogen “blockers”:
- SERMs (selective estrogen receptor modulators) that can act as an agonist or an antagonist on the estrogen receptors
- Aromatase inhibitors that block enzymatic production of estrogen from androgen (estradiol from testosterone, for example)
- GnRH analogs which shut down release of hormones from the pituitary that would stimulate the ovary to produce estrogen
The original reason for this post was to talk about the effects of sex steroids on bone. Okay, so why would we care about blocking estrogen when we talk about bone health in men, whether they be trans or non-trans? After all, men have testosterone (well, many do anyway). What’s the big deal about estrogen? Well, read on for the exciting answer…
Sex steroid hormones and their action on bone
Bone is a dynamic tissue. During growth, there is bone modeling, which results in an increase in bone mass. In adulthood, there is bone remodeling, which, in the “normal” state, is a balance of bone resorption and deposition, called bone homeostasis. Also, there are different types of bone (woven & lamellar), bone structures (cortical, trabecular, etc) and other details of bone biology that I won’t go into here. For the purposed of this post, I am making a very simplified description of bone biology, so if you would like to know more, you can read about basic bone biology or, if you want a little more to sink your teeth into, there’s this free review article on bone biology.
After all the talk about estrogen and some about testosterone, we can look at how these hormones affect bone. The importance of estrogen for bone health in natal females is well-known. Just about all of use have a female relative who must remain vigilant about her bone health following menopause because the significant drop in her estrogen levels can lead to osteoporosis. In other words, in females, estrogen supports balanced bone remodeling. Without estrogen, bone resorption outweighs deposition and the bone becomes weak.
The importance of sex steroids for bone health in natal males, however, has offered up a few surprises relatively recently. The assumption for years was that testosterone maintained bone health and bone mineral density (BMD) in natal males. Compared to natal females, natal males put down more bone during growth, have a greater peak bone mass, lose less bone with aging and have a relatively stronger skeleton, all of which were attributed to the effects of testosterone. Because estrogen levels in the blood of natal males are relatively low, at the level of those seen in post-menopausal natal females, the importance of estrogen on male bone health was considered to be insignificant. Mother Nature, however, taught us different lesson.
In the mid-1990s, several reports of men with mutations in their genes for estrogen receptor alpha (ERα) or aromatase provided a surprise. Even with testosterone coursing through their veins, the men with these genetic mutations had severe osteopenia (low BMD) and failure of the epiphyseal plates to fuse in their long bones. If that wasn’t surprising enough, the men with mutations of their aromatase genes responded to replacement therapy with estrogen with an increase in BMD and closure of the growth plates of the long bones.
In other words, estrogen, aromatized from testosterone locally in the bone tissue and acting through the ERα, is required in males for optimum bone maturation.
The importance of estrogen for bone maintenance in natal males was also shown in cases where the individuals were being treated for androgen-sensitive prostate cancer with GnRH analogs. Even though testosterone was absent in those males, BMD was maintained with raloxifene, a SERM that is an ER agonist in bone.
That isn’t to say that testosterone isn’t important for bone in males. Studies with men and animals provided evidence that testosterone is important for deposition of cortical bone in growing males and works to inhibit resorption of bone and maintains bone deposition in adult males. For example, in men treated with a GnRH analog to artificially induce hypogonadism (lack of testosterone), administration of both estrogen and testosterone resulted in a bone metabolism that was closest to the normal state. These actions of testosterone on bone are communicated via the androgen receptor (AR) and are independent of the aromatization to estrogen and its actions thereof.
What does this all mean for transmasculine people who are taking estrogen blockers?
When I began this topic, in Part 1, I said that estrogen blockers can matter when it comes to bone. Or not. It really does depend.
First, for guys who have had their ovaries removed and are not on testosterone hormone replacement therapy, for whatever reason, their bones are at risk for osteopenia/osteoporosis, similar to severely hypogonadal males or post-menopausal females — in other words, just like any individual who lacks both androgen and estrogen.
With regard to estrogen blockers, I’m going to leave the SERMs out of the discussion because my impression is that the major type of estrogen blocker used to treat trans guys is in the GnRH analog group.
One would not expect issues with bone if a guy taking a GnRH analog was also on testosterone hormone replacement therapy. The testosterone would have direct effects on bone and would also be aromatized to estrogen, which would support bone homeostasis. (I won’t speak about trans children on GnRH analogs to delay puberty because other hormones are involved in bone growth in those cases.)
This brings us to the final estrogen “blocker” — the aromatase inhibitors. Even if a guy is taking testosterone hormone replacement therapy, concomitant treatment with an aromatase inhibitor would not allow aromatization of androgens, so there would not be any estrogen present to support bone homeostasis. Intuitively, one should be concerned about osteopenia/osteoporosis in this case. There is clear evidence of osteoporosis in post-menopausal females who take aromatase inhibitors to treat estrogen-sensitive breast cancer. However, the jury is still out on pre-menopausal females who take aromatase inhibitors for the same reason.
Therefore, trans guys who are considering taking aromatase inhibitors to block estrogen, even if they are on testosterone, should have a serious conversation with their doctor about their bone health and whether their BMD should be monitored during the course of treatment.
And there you have it– the slimmed down version of estrogen blockers and bone homeostasis. There are a few references at the end here for those who would like to dive into the subject a little deeper. For information on this subject as it pertains to trans men, I highly recommend the section in Dr. Nick Gorton’s et al. free book, “Medical Therapy and Health Maintenance for Transgender Men: A Guide for Health Care Providers,” pages 59-61.
Sorry there aren’t photos and more in-depth details in this post, but I had to write it in a rush. I gotta cut outta here — I’m Batman’s wing man for his date tonight…
References for this post:
Medical Therapy and Health Maintenance for Transgender Men: A Guide for Health Care Providers, 2005, Gorton N, Buth J, Spade D, pages 59-61.
Regulation of adult bone turnover by sex steroids, Frenkel B, Hong A, Baniwal SK, et al., 2010, J Cell Physiol 16 Apr [Epub ahead of print].
Sex steroids and the male skeleton: a tale of two hormones, Callewaert F, Boonen S, Vanderschueren D, 2010, Trends Endocrinol Metab 21(2):89-95.