Progesterone may not be only beneficial or ineffective for trans women – for some, it can be actively harmful

Disclaimer: I am not a medical professional and this is not medical advice.

Zinnia JonesEver since I came out and started HRT in 2012, I’ve found it important to document and share my experiences as a trans person with every aspect of this process, not only to aid in cis people’s understanding of our lives but to offer other trans and gender-questioning people points of similarity and comparison with which to identify themselves. This has included experiences which haven’t been documented extensively or at all in official literature on what to expect, such as pre-transition chronic depersonalization that remits upon transition, but which turn out to be shared by many trans people once we begin comparing notes on our lives. In keeping with that tradition, I find it necessary to share the results that I and other trans women have seen from a much-debated element of HRT: progesterone.

Hormone therapy regimens for trans women and transfeminine people consist of an antiandrogen (discontinued if orchiectomy or vaginoplasty is performed) and estrogen, whereas progesterone or synthetic progestins are typically neither recommended or disrecommended as a part of routine treatment. Authoritative medical sources generally neither state that progestogens must be included or must not be included as part of feminizing HRT; its inclusion is optional, and results seem to be individually variable. The effects of progestogens – encompassing bioidentical progesterone itself as well as synthetic progestins acting on the progesterone receptor, such as medroxyprogesterone acetate (MPA) and cyproterone acetate (CPA) – on the feminization process have not been widely studied, although CPA is commonly used as an antiandrogen outside the United States, and there is evidence that MPA can augment the antiandrogenic effects of spironolactone (Jain, Kwan, & Forcier, 2019). The UCSF Transgender Care & Treatment Guidelines note that trans women anecdotally report improvements in breast development, mood, and libido when using progestogens, while also pointing out that “some patients may respond favorably to progestogens while others may find negative effects on mood.” In the context of this almost entirely anecdotal body of knowledge on the effects of progestogens as part of feminizing HRT, I believe it is crucial to add my own anecdote: severe depressive and anxious symptoms associated with progesterone and progestins.

I began taking bioidentical progesterone at a dosage of 100mg/day in mid-2013, with little noticeable effect other than a greater ease of weight gain; it wasn’t possible to tell whether the resulting feminine fat distribution and body shape was due to progesterone itself, or simply due to weight gain in the context of typical female-range testosterone and estrogen levels. In late 2013, my progesterone dose was increased to 200mg/day, and within a couple weeks I began to experience severe anxiety and elevated stress levels on a daily basis. Everything in life, even the smallest tasks or events happening around me, felt unbearable and impossible to cope with. Enjoyment of anything seemed to become completely out of my reach, with a pall of utter hopelessness cast over every single day. I found it increasingly difficult to manage my stress – it was difficult for others to be around me, and it was difficult to be around myself. Once I recognized that the onset of these symptoms seemed to be associated with the increase in my progesterone dose, I switched back to my previous dose – and went on antidepressants for the first time in my life. The symptoms began to remit, and gradually I felt a return to my usual self, with a newfound gratitude for simply being able to feel okay on a day-to-day basis and find optimism and hope for the future.

More recently, I began taking synthetic progestins last fall, both for their progestogenic and antiandrogenic effects as well as to see whether this affected me any differently from bioidentical progesterone. Physically, the effects were more noticeable than those of progesterone: my skin became even softer; my sex drive was suppressed to a point that I could hardly summon a sexual thought even deliberately; my breasts felt firmer and fuller, although this was transient and seemed to be a result of fluid retention. Mentally and emotionally, the results were catastrophic – a few weeks after starting, my mood descended to a state of unalloyed misery. Just doing anything at all felt like it took an extraordinary effort; I began to perceive everything as so stressful I could hardly cope with it. I would start crying several times a day for any or no reason, and unlike my usual experience of crying, I found no relief from it afterward. There was no respite from this state – I woke up miserable and went to bed miserable.

I started to have social anxiety, which I didn’t recognize at first because it’s not a form of anxiety I had ever experienced to a substantial degree. I felt uncomfortable and self-conscious in public for no clear reason, and just wanted to avoid it entirely, whereas before I would have found this positive and refreshing. My sense of self-image worsened, and I just felt ugly when I looked at myself, an experience distinct from dysphoria about my gender. I even began having frequent episodes of shouting and flailing in my sleep, something that had hardly ever happened before. Every night, I had seemingly constant vivid dreams to a far greater degree than usual. During the day, I felt like I was somehow losing touch with reality, and even losing parts of my own self. It was becoming unbearable to imagine going through the rest of my life suffering like this, and any beneficial physical changes meant nothing when I couldn’t be happy about anything.

I’m used to the usual forms that my mental health struggles take – and eventually I had to recognize that this was not my familiar brand of being unwell. This was something else entirely. After a few months, I discontinued progestins, and within a few days I could feel my mood starting to lift. Everything began to feel possible again, doable again. I started to be able to feel happy and just enjoy myself, confident rather than self-conscious, whole as a person rather than disintegrating. I’ve been on an upswing since then, and the realization that I won’t have to feel that way for the rest of my life has itself been such a relief.

I don’t believe that this adverse reaction to progesterone or progestins is new or anomalous – other trans women have experienced such effects as well. One trans woman I know had similar depressive and anxious symptoms only when taking 200mg of progesterone, but not 100mg. When I inquired about these experiences on social media, several other trans women reported having severe depression after starting progesterone, CPA, or MPA; others noted positive effects on mood and libido, or no noticeable effects at all. So this is not to say that these adverse effects are universal, or even common – only that they are something that can happen among some trans women, and that this is a possibility to remain aware of when taking progestogens.

In what circumstances might this be a concern? CPA is used as a routine part of feminizing HRT outside of the United States; those experiencing harmful mood effects from this may need to switch to other antiandrogens. In a study of MPA added to spironolactone for testosterone suppression, 12.8% of those taking MPA reported experiencing mood swings (Jain et al., 2019) – although MPA was associated with significantly decreased T levels, severe mood issues may outweigh this benefit for some trans women. Dr. William Powers recommends use of bioidentical progesterone at 200mg/day as part of feminizing HRT (Powers, 2020); this may have unacceptable mood effects for some trans women. Additionally, the possibility of serious negative mood effects may provide a new perspective on the practice of cycling of progestogens by taking them for only 10 days a month, something which, much like the use of progestogens generally, has little or no evidence to recommend for or against it. For some trans women, this may be a way of achieving desired progestogenic and/or antiandrogenic effects, without the same degree of impact on mood that would come from taking these medications daily.

The current state of knowledge on use of progestogens in trans women is so thin that it seems impossible to make well-supported recommendations on whether we should or shouldn’t take these medications, which ones we should take or avoid, and which dosages to take. But what we can say is that certain effects have been known to happen, and that trans women should know about these when making decisions about including progestogens as part of their HRT. 

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About Zinnia Jones

My work focuses on insights to be found across transgender sociology, public health, psychiatry, history of medicine, cognitive science, the social processes of science, transgender feminism, and human rights, taking an analytic approach that intersects these many perspectives and is guided by the lived experiences of transgender people. I live in Orlando with my family, and work mainly in technical writing.
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3 Responses to Progesterone may not be only beneficial or ineffective for trans women – for some, it can be actively harmful

  1. Kay says:

    I mean… it’s a period. Progesterone is largely implicated in the mood effects of periods in people who menstruate, and it should be no surprise that many trans women experience the same thing. A period that never ends is going to be hellish. When I was taking bioidentical P I cycled it similarly to a menstrual cycle. I found that when I tuned in to my body, I felt both a need to stop taking it after I had been on it for around a week, and then a desire to get back on it about a month later. Without putting any conscious intention to it my body organically recognized a need to cycle.

  2. It’s good to know potential side effects. Most of the trans-related research on this, such as it is, is related to physical effects.

    It’s interesting to me how much difference we are slowly discovering in the process of providing hormones to trans women. Between patches, pills, injections, pellets, do you add antiandrogens, and if so, which kind, and if progesterone, which kind?

    I’ve seen papers elsewhere talking about the negative effects one can get from a metabolite of progesterone: allopregnanolone. I guess much like acetaldehyde from drinking, if you have low enough doses for your physiology, the excess is never converted, or it’s cleared quickly, but enough excess can force it down another metabolic pathway with deleterious results.

    I got prescribed progesterone in a cycling dose simply due to my age and the purported preventive effects it can have vis-a-vis thrombosis (I saw your posting on that one – intriguing) and estrogen-related cancers. Cycling may not be necessary, but it does permit me some interesting observations and… it’s nice to be able to have late-night snacks for two-week periods and keep the medication cost down, truth be told :)

    I’ll do some informal introspection on my anxiety level on and off just to see.

    My impression from timelines of the myriad trans people I follow on social media is that progesterone does seem to help breast development in more than a water retentive way, but that it doesn’t work for everyone.

    Everyone is biochemically different. It was funny to find out, for example, that I’m completely immune to the effects of diuretics – not just spiro, but two others that were prescribed by an incompetent GP for the swelling of what turned out to be a broken foot. So taking spiro just did not make me pee. Go figure :)

    Thanks for your YouTube videos from long ago, by the way. They were invaluable <3 I've been trying to give people resources to try to combat the gender essentialist/gender critical crowd and it was nice to trip across you here.

  3. The responses trans women experience with progesterone is quite individual. Especially with oral progesterone capsules — generally, the response can be divided into three groups, one with a negative “anxious” reaction such as you experienced, and another with feelings of lethargy or lowered energy or mild sedation, and another with feelings of relaxation and generally positive uplifted mood. The obvious solution is that self experimentation is clearly called for — and that physicians should not force oral progesterone on their patients if they experience negative symptoms. However the better solution may be to take progesterone by IM injection, twice a week. By bypassing the gastric system, the wholesale conversion of progesterone to allopregnenolone is eliminated — eliminating some of the side effects. In a few patients, IM injection* of progesterone can also lead to uncomfortable mood swings, but some anecdotal experience suggests that injection of progesterone about 24-36 hours after estradiol injection leads to less swings overall and may maximize the chances of getting into the “elevated mood” effects of progesterone. Again, this can be a matter of individual testing. So let me urge you to not assume that your results are typical, nor that all methods and schedules of taking progesterone will result in the same effects. [* note: even though subcutaneous injection of estradiol is an excellent administration method, group experience suggests that SubQ may not be suitable for progesterone.]

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