Synthetic progestogens (Androcur...)

Progestogens is the third group of sex hormones after androgen and estrogens. We will differentiate here between “natural” (bioidentical) progestogens (progesterone is the main one) and synthetic progestogens, developed by the pharmaceutical industry for different purposes (namely contraceptive medications, and anti-androgen medications).

Progestogens’ main function, for ciswomen and AFAB people, has to do with ensuring the means and continuation of pregnancy: regulate the cycle, maintain the endometrial tissue of the uterus during and after ovulation, allow lactation…

For transfem people, only the secondary effects of progestogens are of interest. Those effects includes:

• Reduces the production of testosterone (anti-androgen)
• May help finalize breast growth by developing terminal lobules necessary for lactation.
• May terminate/limit breast development if taken before Tanner stage 3.
• Can cause the chest to swell.
• May alter water retention by the body.
• May increase appetite.
• May promote fat accumulation and weight gain.
• May increase metabolism.
• May promote sleep.
• Can increase or on the contrary decrease the libido.
• Can limit or on the contrary aggravate hairiness
• May cause drowsiness and dizziness (only for progesterone).
• May increase the sensation of dysphoria.
• May increase the risk of depression.
• Increases the risk of breast cancer (particularly for synthetic progestins).

Most of the negative effects given above are associated with synthetic progestogens.

Synthetic progestogen:

So, why would you take synthetic progestogens? Because they can work as very efficient anti-androgen, thanks to the natural negative feedback: more of any sex hormones leads to less of endogenous sex hormones. To the body, a synthetic progestogen is read as any other sex hormones: enough of it will start the negative feedback mechanism.

This is true of bioidentical progesterone and synthetic progestogens. The difference being that bioidentical progesterone has a weak effect of negative feedback (you would need a lot to start it), when synthetic progestogens have been developed in order to have a very strong effect as they last much longer in the body.

Androcur

The most potent and widely prescribed synthetic progestogen is Cyproterone Acetate, sold under the name of Androcur. The use of Androcur is banned in the US because of its risks of liver failure, in favor of Spironolactone. In the UK, GnRHa are largely prefered. Androcur remains the most prescribed anti-androgen medication in Europe.

Androcur accumulates the strong anti-androgenic effect through negative feedback, with a small androgen receptor antagonist, plus all progesteronic effects - especially those of synthetic progestogens. It carries a load of adverse side effects, namely prolactinemia (possibly leading to bone problems) and meningiomas (tumor of the meninges). In some countries, like France, a doctor cannot prescribe Androcur without written consent of the patient, and regular MRI scans.

It is also associated with liver failure, and depression.

If you cannot access another medication, you should try to limit the doses as much as possible. Studies have shown that Androcur reaches its maximal effect at 10mg/day. It is unnecessary to exceed this dose, and that would only expose you to more risks.

Pros:

• Very efficient anti-androgen
• Stronger progesteronic action than bioidentical progesterone

Cons:

• Important risks of depression
• Associated with drastic fall of libido
• Risks of prolactinemia, liver failure, meningiomas
• Might perturb breast growth if taken before Tanner stage 3

Androcur is one among many synthetic progestogens. All the others have their bunch of undesired side effects, mostly - at different degrees - depression, liver failure, and prolactinemia. Those drugs include Levonorgestrel, Dydrogesterone, MPA, Norethisterone…