Black Cohosh for Transsexual HRT

Summary: Black cohosh, when combined with hormone blockers, may allow people to transition to being "hormoneless." I tried it and found cohosh effective at preventing the depression-like symptoms that normally make being hormoneless unfeasible, but further research is needed to see if it also prevents the osteoporosis caused by having no estrogen.

Background

Black cohosh (Actaea racemosa, Cimicifuga racemosa) has been known to the trans community for a while, mostly as a suggested "herbal estrogen" alternative to synthetic bioidentical estradiol. This is, according to current scientific literature, a very bad suggestion. An in vitro study [1] and a study in rats [2] found that black cohosh has no estrogenic activity whatsoever. This means it will not feminize you, it will not lower T production by the testes, and just in general it won't do anything for someone with non-menopausal hormone levels.

However, there is a reasonably sized body of literature, summed up nicely in an EU report [3], which points to cohosh being effective at relieving various symptoms of menopause - hot flashes, cramps, headaches, and lowered energy/depression (called "neurovegetative" symptoms in some literature). There is also some support for it preventing osteoporosis, but possibly not enough to make it a proper substitute for estradiol (see section 3.1.2 of [3] and p. 19 of [4]). All sources agree that black cohosh is very safe - there's a few scattered reports of liver issues, but it's hard to attribute those to the cohosh specifically (and it's not like any form of HRT is 0-risk).

This is important for trans people of all ages because menopausal symptoms are actually just the symptoms of having near-0 estrogen and near-0 testosterone, which I will be calling "eunuch levels". I see people asking a lot about the possibility of "having no hormones," or CAMAB people asking about taking just antiandrogens and not estrogen, or asking if there's a way to feminize skin and hair growth without growing breasts. Generally the response is that this is impossible, because the menopausal symptoms make life miserable, and in the case of osteoporosis, are quite dangerous. However, I think cohosh might open up the possibility of a transition to eunuch as a healthy and sustainable endocrinological sex.

What Is Being a Eunuch Like?

First, a combination of GnRH agonists/antagonists (i.e. "blockers") and black cohosh should let anyone, regardless of "biological sex," transition to eunuch. Here's my guesses as to the physical changes that would occur:

Experiment

Me and a friend tried having eunuch levels and taking black cohosh for a month, to see if it would actually work at preventing menopausal symptoms.

The first challenge with trying to be a eunuch is completely blocking your body's endogenous (i.e. "naturally produced") hormones. My normal HRT routine is 3mg/day of sublingual estradiol plus 50 mg/day of bicalutamide. Although the bica completely blocks the effects of testosterone, it doesn't stop the production of testosterone, meaning that when I stop taking my estradiol (and it therefore stops suppressing my testosterone production), I have enough testosterone getting aromatized into estrogen to keep my estrogen levels above "eunuch." To fix this, I started taking buserelin, a GnRH agonist that will actually suppress the production of testosterone. I was using the nasal spray at a ~1,200 μg/day dose, which isn't quite enough to get down to eunuch levels of testosterone, so I continued taking bicalutamide alongside it, although at a 25 mg/day dose so I could share with my fellow lab rat (referred to as FLR from here on).

Participant Info

Me: perisex transfem, on HRT for about 3 years prior to starting the experiment, pretty fully feminized (body & facial hair, body fat, breast growth, etc. have been static for around a year)

FLR: perisex transfem, never taken any HRT before.

Drug Doses

Drug Schedules

  1. 27 days of "buserelin comeup": Buserelin is a GnRH agonist, so it works by overstimulating your body's "produce more sex hormones" signal receptors until you build up a massive tolerance to that signal, so that your body's attempts to signal an increase in hormone production go unnoticed. What this means practically is that for the first week, buserelin actually increases production of endogenous hormones, and doesn't work as a blocker until sometime between weeks 2 and 4. So during this period, I took estradiol, bicalutamide, and buserelin, and FLR just took bicalutamide and buserelin.
  2. 14 days of no hormones: Both me and FLR just took buserelin and bicalutamide for these two weeks, to get a baseline for how bad it is to have no hormones without black cohosh support.
  3. 13 days of estradiol: Both me and FLR took estradiol, buserelin, and bicalutamide, in order to "reset" after the no-hormones period.
  4. 27 days of black cohosh: Both me and FLR took black cohosh, buserelin, and bicalutamide. Test ended after one month because buserelin is expensive, and because of risk of osteoporosis.

Other details

All experiment details (including data analysis methods) were decided in advance. The experiment mostly took place while both me and FLR were in pretty stable life situations - no moving, changing jobs, etc. - except that I moved two weeks before the end of the experiment, so most data from after that has been ignored.

Results

Subjective

Me

I kept a small note in which I recorded any particularly noticeable symptoms. Hot flashes were too fleeting to be written about, but I remember having plenty during the no hormones period and a couple during week 3 (but not 4?) of the black cohosh. Also un-noted was the many minor headaches I had during the no-hormones period, which did not occur during the black cohosh period.

Notes (days are 1-indexed, i.e. the day I started taking black cohosh would be "black cohosh day 1"):

Overall, I would say that having no hormones wasn't unbearable by any means, but my quality of life was noticeably a bit worse, and the cramps made me not want to do anything too strenuous. The increased sleepiness was also a bit annoying because I just had less time every day, I was sleeping more. In contrast, being on black cohosh felt just like normal (i.e. being on estrogen), save for some occasional and very brief (2-3 minute?) hot flashes, which don't really interfere with my functioning.

FLR

FLR experienced only slight subjective changes - just being unusual tired and burnt-out at the end of the day during week 2 of no hormones. They experienced no hot flashes, cramps, etc. However, they did get some noticeable physical changes from starting HRT. On estrogen week 2 they started having breast growth soreness, and some breast budding was visible. After switching to black cohosh, the soreness stopped and it doesn't seem like there was further growth, although it's hard to tell. There were also noticeable changes to skin - FLR's skin got softer and cleared up a little, and the reflectance of their face got brighter.

Objective

I also wanted to gather some less-prone-to-bias data, so for the entire duration of the study I tracked my sleep (counted as "laying in bed, trying to sleep, not on my phone or anything else") and wake times, wore a smartwatch to track steps and heart-rate (by the minute) during waking hours, and used an app I made to poll me every few hours on my current "lethargy," on a scale of 0-3, where 0 meant "out and about and enjoying it," 1 meant either "at home being productive/hanging out with friends" or "out and about but I wanna go home", 2 meant "wasting time (e.g. scrolling online, watching TV)", and 3 meant "doing nothing, rotting, possibly nonverbal". I had the notifications show up on my watch so it would always be in real-time, and not affected by how often I check my phone.

The results show that on every metric but steps, the first two black cohosh weeks represented a more active lifestyle than the last two weeks of buserelin comeup (which I'm using as my control due to the regularity of my hormones during that time), and both represent a significantly more active lifestyle than no hormones and no cohosh. The statistics are summed up in the following table, where an asterisk denotes a statistically significant difference from control (using Welch's t-test, p<0.05):

Condition Steps per day Average heartrate (BPM) Average lethargy (lower = more active) Percent of time spent asleep Time per day spent asleep vs control
Control (estradiol) 5594 76.3 0.89 33.6% n/a
Eunuchmoder (no hormones or cohosh) 4092 74.5* 1.20* 36.0% +34 minutes
Cohosh (cohosh) 5364 77.0* 0.84 30.0% -52 minutes

All the BPM differences are statistically significant because that's what happens when you have 10000 data points 🤪 and I didn't know how to calculate significance for the sleep percentage, so I didn't. Here's some visualizations:

Box plot of daily steps. cohosh and eunuch are both fairly compact distributions, with cohosh averaging many more steps, and control has a median very close to eunuch, but a long tail, including a higher third quartile than cohosh. Pie chart of control lethargy scores. 23.6% of scores are 0, 65.5% are 1, 9.1% are 1, and 1.8% are 3. Pie chart of eunuch lethargy scores. 20.4% are 0, 38.9% are 1, 40.7% are 2, and 0% are 3. Pie chart of cohosh lethargy scores. 38.7% are 0, 38.7% are 1, 22.6% are 2, and 0% are 3.

Potential Science Issues

This study was extremely exploratory and probably not even being worth called a "study" - it was not blinded, n was 2 (1 for the objective data!), and very few of the results were significant. There's also a slight integrity issue - I originally used the 2 weeks of estradiol in between eunuch and cohosh as the control data, which yielded no significant difference from eunuch, but a significant difference from cohosh (i.e. cohosh was significantly better for my mood than control). This made little sense to me and didn't agree with my subjective experience, so after some thought, I attributed this to the fact that the first week or so of that estrogen period I was still recovering from having no hormones (and dealing with the effects of an estrogen spike), and switched the control to be the last 2 weeks of buserelin comeup instead. But it's still kinda p-hacking so whoops. The code I used for data analysis is available here.

Conclusions

Despite the science issues, I think this is a substantial and promising first result! The main issue is lack of knowledge about the osteoporosis issue, so the next step would be to try using cohosh as a eunuch for a long time, while getting monthly bone density tests. I plan to do this, but first I want to go back on estradiol for a while to get a good baseline bone density measurement, and also I would like to get orchi, because of issue number 2: buserelin is kinda expensive DIY ($50 a month + shipping), and I don't think most doctors would be willing to prescribe it to an adult. If anyone knows a cheaper way to achieve eunuch levels, that would be very helpful in making transitioning to eunuch a more accessible option.

The other issue is, of course, lack of data. I wouldn't really "recommend" this to anyone, but if you understand the risks and try it yourself, please share your experiences! The more we share, the more we know :3

Also, do not try maintaining eunuch levels unless you've already gone through a puberty - it will probably fuck up your growth in a really dangerous way.

Bibliography

[1] Beck V, Unterrieder E, Krenn L, Kubelka W, Jungbauer A. Comparison of hormonal activity (estrogen, androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy. J Steroid Biochem Mol Biol. 2003 Feb;84(2-3):259-68. doi: 10.1016/s0960-0760(03)00034-7. PMID: 12711012.

[2] Burdette JE, Liu J, Chen SN, Fabricant DS, Piersen CE, Barker EL, Pezzuto JM, Mesecar A, Van Breemen RB, Farnsworth NR, Bolton JL. Black cohosh acts as a mixed competitive ligand and partial agonist of the serotonin receptor. J Agric Food Chem. 2003 Sep 10;51(19):5661-70. doi: 10.1021/jf034264r. PMID: 12952416.

[3] W. Knöss, Assessment report on Cimicifuga racemosa (L.) Nutt., rhizoma. 2018. ref: EMA/HMPC/48744/2017

[4] Fritz H, Seely D, McGowan J, et al. Black Cohosh and Breast Cancer: A Systematic Review. Integrative Cancer Therapies. 2014;13(1):12-29. doi:10.1177/1534735413477191

[5] Todorov, Alexander. Face Value: The Irresistible Influence of First Impressions. Princeton University Press. 2017