SERMs, or Selective Estrogen Receptor Modifiers, are medications originally designed to treat conditions such as infertility, breast cancer, and osteoporosis in cis women. This family of drugs includes tamoxifen, toremifene, raloxifene, and clomiphene.
To put it overly simply, SERMs work by turning estrogen receptors on or off based on location such as in breast, skin, and/or uterus cells. Each SERM has slightly different effects because of which estrogen receptors they turn on and off.
Raloxifene is approved for the prevention and treatment of osteoporosis and the prevention of breast cancer. Tamoxifen is used to treat breast cancer, to prevent breast cancer in people at high risk, and for breast pain. Toremifene is FDA approved for the treatment of metastatic breast cancer. Clomiphene is used in fertility medicine.
In gender affirming care, we tend to use raloxifene the most.
Raloxifene tends to be better tolerated and have fewer side effects than the others. Plus, it works in ways that align with our goals – it turns off estrogen receptors at the breast and uterus.
In someone with testicles interested in gender affirming care who does not want breast development, raloxifene can minimize the effects of estrogen at the breast and reduce breast growth.
Raloxifene does not cross the blood-brain barrier and was not found to affect the cognition of post-menopausal cis-women who took it for a year. If your goals include mental/emotional changes, you would want to also take estrogen.
It appears to reduce breast development in those also taking estrogen , but does not prevent breast development completely (we’ve noticed this, but we haven’t run any studies, so we can’t say with certainty.) Because it increases estrogen receptor activity in other sites – like the skin – folx may see softer skin even without taking additional estrogen. Bonus!
In someone with ovaries interested in gender affirming care who has difficulty stopping their periods, raloxifene also turns off estrogen receptors in the uterus. It could be helpful in controlling otherwise hard to control cycles.
Most commonly reported side effects of raloxifene include:
- swelling of the hands and feet (3%-14%)
- hot flashes (8% to 29%)
- infection (11%)
- joint pain (11% to 16%)
- leg cramps (≤12%)
- muscle spasms (≤12%)
- flu-like symptoms (14% to 15%)
A less common scarier side effect is blood clots (1-2%) – it can cause a blood clot in 1 to 2 out of every 100 people who take it.
Other SERMs in gender affirming care
Tamoxifen is occasionally used in gender affirming care to reduce breast development after having previously been on hormones that caused breast development. It tends to have more discomforting side effects.
Toremifene and clomiphene do not currently have much use in gender affirming care. We don’t use toremifene due to cost and accessibility, and we don’t use clomiphene because it does not work on receptors in a way that is beneficial to us.
Evidence-based medicine and informed decision making
At QueerDoc, we practice evidence-based medicine and informed decision making.
We go into detail about what this means for our practice here: https://queerdoc.com/
The short story is that we want you to be able to make the best decision for your body based on the best information we can provide you about risks and benefits. Often in gender affirming care we don’t have a lot of robust evidence. So, use our best judgement based on the information we have about similar care in cis populations, information and opinions from other experts, and from our own observations in clinical practice.
The use of SERMs in gender affirming care is all based on theory: we don’t have any great research articles or trials. If you’re interested in SERMs, we’d discuss all of this in detail – what we do and don’t know, what studies in cis populations might be applicable to you, and what we’ve observed in clinical practice to provide a the information that will help you make the best decision for you.
Duschek EJ, Gooren LJ, Netelenbos C. Effects of raloxifene on gonadotrophins, sex hormones, bone turnover and lipids in healthy elderly men. Eur J Endocrinol. 2004 Apr;150(4):539-46. doi: 10.1530/eje.0.1500539. PMID: 15080785.
Uebelhart B, Herrmann F, Pavo I, Draper MW, Rizzoli R. Raloxifene treatment is associated with increased serum estradiol and decreased bone remodeling in healthy middle-aged men with low sex hormone levels. J Bone Miner Res. 2004 Sep;19(9):1518-24. doi: 10.1359/JBMR.040503. Epub 2004 May 3. PMID: 15312253.