Categories: Science!/ TransSci

magnus_pyke_scienceFollowing up on yesterday’s post, I went looking today for information on cyproterone acetate and spironolactone, after seeing it suggested (but unverified) in Wikipedia that one (spiro) was the most commonly prescribed anti-androgen used for HRT in the United States and the other (cypro) was the most commonly prescribed internationally. Is this true? And if so, why?

For drug information in the United States, the best place to start is usually the Physician’s Desk Reference (PDR), which is pretty much the medical standard for prescription drugs in the U.S. Looking into this question quickly reveals why spiro may be more widely prescribed in the United States: as it turns out, cyproterone acetate hasn’t been approved by the FDA, and the PDR only contains FDA-approved drugs. Thus, the mystery is solved: they don’t prescribe cypro in the U.S. because they can’t. So far, I haven’t found a clear explanation why the FDA hasn’t approved the drug. It’s been around for half a century, so it’s likely been considered and rejected for some reason or other. [It’s worth noting that the FDA’s lack of approval means cypro cannot be used for any treatment in the United States, not just HRT.] But until it is, American trans women don’t have it as an option.

As for why international doctors favor one over the other? Again, the reasons are not immediately clear. Multiple studies of the two drugs as competing treatments for hirsutism found no significant benefit of one over the other in that use case; and there’s no clear study I can find in PubMed favoring one over the other for HRT (or even comparing the two as competing MtF drugs). In addition, a paper by Moore, et al (2003) that offered a comprehensive overview of endocrine treatment options for transsexuals presents the two as more or less interchangeable options for the anti-androgen component of HRT. It may simply be that, outside of the U.S., doctors have had more success with cypro. Given that spiro is also a diuretic may also be one reason why cypro is favored by patients when the choice is available. But in the U.S. spiro is the best choice. [The other more commonly prescribed anti-androgen in the U,S., finasteride, is prohibitively more expensive and is viewed, at least by doctors I’ve spoken with, as being less effective overall for HRT. ]

It’s a shame that doctors in the U.S. don’t have the option of cypro, considering how common and effective it appears to be internationally. Maybe someday, some pharmaceutical company will find reason to re-seek FDA approval. Until then, I guess American MtFs will just have to take what they can get (and stay close to a bathroom!).

This post is occasionally updated to maintain its content. Last revision 05/01/2014..]



From what I understand, cypro can have some severe side effects that result in liver damage, whereas spironolactone is relatively safe. I don’t know that either help a lot, since estradiol does a pretty good job of reducing testosterone on its own. I take spiro, finasteride, and then estradiol for my HRT regimen.

Jenn says:

At 47 I stated self medicating. I opted for XXmg/week IM estradiol valerate, XXXmg Micronized Progesterone per month IM, Xmg Duasteride every other day, XXmg aspirin daily.
I started out with XXXmg/daily spiro and found myself constipated and gaining weight. After a lot of reading about spiro effects, I decided I was also becoming hypothyroidic (maybe due to spiro, age, or estrogen dominance). I weaned myself off spiro while switching to cypro (foreign mail order for everything – ALC or IHP). Yes, spiro is only 1/4 the price of cypro, but after a year on cypro XXXmg, I dropped it to XXmg and haven’t had any side effects (unlike Sprio). Spiro caused major sweating when working out. Cypro did not.

FYI – Adding Progesterone and spiro both seem to cause weight gain as far as I have experienced. Cypro and Estrogen has not changed my weight at all. Taking a thyroid supplement picked up my energy level but affects my ability to sleep well. *** YMMV ***

Testicular atrophy was complete after a year, and length went from 6″ flacid to <1.5". What is left is soft enough to press flat under most undies or bikinis. This will probably not bode well for SRS.

Breast developement (nothing to a 38c) was fast and complete in less than a year, but they were conical in shape, and only after 6months or more on progesterone (IM), did they round out nicely. So (IMHO) Progesterone is necessary only to round out the breasts, not to initially develop them. I've also experienced lactation for a couple months when I had stopped Progesterone, which didn't shock me as it's a normal "pregnancy hormone shift" reaction.

BTW…my breasts did increase in size with minor weight gain (<5lbs) and just estrogen, but they really rounded out when I gained 20lbs later. This seems to be progesterone related. At 195lbs it's very hard to drop weight. I was 170 when I started. So be prepared and lose as much as you can before starting hormones, and especially before starting progesterone as you will round out nicely at the expense of gaining what I call "pregnancy weight". Once you start P, you appetite will increase and "boredom eating" will come calling.

Thank you for sharing your experiences. I did choose to edit out the dosages before approving your comment because I don’t condone self-medding.

My own experience with the cipro/progesterone combo is not like yours. I haven’t had bloating or weight gain; in fact, in the first three months of HRT I’ve actually lost weight. As you say, YMMV. My progesterone isn’t micronized, though, and I seem to hear more stories of problems with that version of the drug.

raquel says:

I read several things that made Cypro sound a bit stronger than Spiro, and only hypothetical concerns about liver damage. Also several sources have noted a mild progestin effect of Cypro. But I looked pretty hard and I don’t think Cypro has ever even been submitted to the FDA. I would guess it’s just because no drug company is pushing for it.

Personally, when I was self-medicating, I was on a fairly standard dose of Spiro and just couldn’t stand how dehydrated I felt all the time (not helped by the fact that I lived in Phoenix at the time). I switched to Cypro and liked it a lot more.

I’ve been seeing an endocrinologist for a year now, and I switched back to Spiro since he couldn’t prescribe Cypro. I used to never really be thirsty. I’m a bit annoyed by having to drink so much water – 64oz or more at work each day, then about another 32oz in the evening. That’s not counting meals, and I usually take my meds with Gatorade. And I have to get up to pee an hour or two before I would prefer to wake up most days, which screws up my sleep.

But last week my endocrinologist said I should bump my Spiro dose down a bit because my T was down to 9 and there was no need to take so much. So that should help. But Spiro comes in 100mg and 25mg pills, and I have a bunch of 100s left. and the math would involve me quartering pills to keep using what I’ve got.

Cest la trans 🙂

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