The popular treatment combinations related to M-to-F hormone therapy are:

Estrogen alone
Adding another type of estrogen. This may cause faster results for some people, but generally not better results in the long run.

Adding an anti-androgen
Adding an anti-androgen may enable one to reduce the estrogen dosage while still obtaining acceptable development in a reasonable time frame, along with very similar results in the long run as opposed to a strictly high dose estrogen regimen. An anti-androgen fights the androgens remaining in the body by either by blocking the actions of androgens, or suppressing their production, rather than seeking to simply overwhelm them as is generally the case with strictly high dose estrogen treatments.

Adding a progesterone
There is some indication that progesterone administered with estrogen may promote extra breast growth by increasing the volume of the lactation and ducting tissues. Some studies relating to birth control pills usage by natal females would seem to show that progesterones administered with estrogens reduce the risk of cancer from administration of estrogens alone. Yet, in some people, synthetic progesterones have a slightly androgenic effect and can apparently even antagonize estrogen absorption, although many believe that the use of non-synthetic progesterone may overcome this adverse effect and provide a healthier balance for an aggressive estrogen dosage.

Medroxyprogesterone, the most commonly used product, has the disadvantage of counteracting some of the beneficial effects of estrogen on blood lipids. Micronized ("natural") progesterone is sometimes suggested as an alternative, but it is expensive, sometimes hard to find, and difficult to obtain without prescription.

Amongst treating physicians, there is uncertainty as to whether progestin products have any positive effect for the transgender individual.

The most common preparation seen in this category is medroxyprogesterone acetate, often branded as Provera. The wisdom of adding a progestin can be linked to mimicking the female hormonal cycle. Additionally, naturally occurring progesterone aids in breast development in genetic females. A decreased incidence of cervical cancer is also noted when a progestin is added into the estrogen replacement regimen. But transgender women do not have a cervix, and the role of progestins in breast development is debated.

This progestogen (trade name Provera) is normally used for treating irregular menstrual bleeding or endometriosis, and its safety record is good. It is widely regarded as the preferred progestogen, at least when the patient is not using combined contraceptive pills as a low-cost source of oestrogen and progestogens. Some patients, however, report slight virilising effects including, occasionally, a return of some degree of male sexual function even in post-orchidectomy subjects, which can be found disturbing; it appears that a proportion of the drug may be metabolised into testosterone in some patients. Medroxyprogesterone acetate is generally less virilising than the testosterone-derived synthetic progestogens (e.g. norethisterone and levonorgestrel), but more virilising than dydrogesterone. If a patient experiences virilising effects with medroxyprogesterone acetate then a switch to dydrogesterone should be considered. A typical pre-op (or early postop) dose (to maximise feminisation) would be 10mg in two doses; post-op 5mg or even 2.5mg may be sufficient to maintain the patient's libido.