Neurological/Psychiatric

• Mood changes can occur, such as the development of depression. However, many trans women report significant mood-lifting effects from HRT as well. In addition, the risk of depressive side effects is more particularly common in those who take progestins. Medroxyprogesterone acetate, in particular, has been shown to cause depression in certain individuals, perhaps due to its possible effect on dopamine levels; though, this effect may be largely reliant on its strong inhibitory effects on sex hormone production, something that would not apply to trans women because they replace their endogenous hormones with exogenous sources.

• Migraines can be made worse or unmasked by estrogen therapy.

• Estrogens can induce the development of prolactinomas, which is why prolactin levels should periodically be monitored in transgender women. Milk discharge from the nipples can be a sign of elevated prolactin levels. If a prolactinoma becomes large enough, it can cause visual changes (especially decreased peripheral vision), headaches, mood changes, depression, dizziness, nausea, vomiting, and symptoms of pituitary failure like hypothyroidism.

• Some people have noticed a feeling of calmness/self-contentment after starting HRT.

• Recent studies have indicated that cross-hormone therapy in trans women may result in a reduction in brain volume towards female proportions.

Metabolic

• Estrogen therapy causes decreased insulin sensitivity which places transgender women at increased risk of developing type II diabetes.

• One's metabolism slows down and one tends to gain weight, lose energy, need more sleep, and become cold more easily. Due to androgen deprivation a loss of muscle tone, a slower metabolism, and physical weakness becomes more evident. Building muscle will take more work than before. The addition of a progestogen may increase energy although an increase in appetite may be seen as well.

 

 

Hormone levels

During HRT, especially in the early stages of treatment, blood work should be consistently done to assess hormone levels and liver function.

Israel et al. have suggested that for pre-castration MTF individuals, therapeutic estrogen levels should optimally be above the normal female range but not more than twice the maximum for the female range, and testosterone levels should optimally fall within the normal female range. However, before castration, it may prove difficult to the extent of being impractical to fully suppress testosterone levels, in which case they may be allowed to fall between the high female and low male ranges instead. In post-castration MTF persons, Israel et al. recommend that both estrogen and testosterone levels fall exactly within the normal female ranges. See the table below for all of the precise values they suggest

Hormone	Bio. female ref. range	Bio. male ref. range	Optimal trans. female (MTF) range	Optimal trans. male (FTM) range
Estrogen (total)	40–450 pg/mL	< 40 pg/mL	400–800 pg/mL (pre-castration)40–400 pg/mL (post-castration)	< 400 pg/mL (pre-castration)< 40 pg/mL (post-castration)
Testosterone (total)	25–95 ng/dL	225–900 ng/dL	95–225 ng/dL (pre-castration)25–95 ng/dL (post-castration)	225–900 ng/dL (pre-castration)225–900 ng/dL (post-castration)

The optimal ranges listed for estrogen only apply to individuals taking bioidentical hormones (i.e., estradiol, including esters) and do not apply to those taking synthetic or other non-bioidentical preparations (e.g., ethinyl estradiol or conjugated equine estrogens (Premarin)).

Male and female reference ranges for hormones and other compounds are not exact and usually vary slightly depending on the source referenced. The same applies to optimal MTF (and FTM) ranges, naturally.