Feminizing hormone therapy

Question 1

The anti-androgens typically used are what ?

Answer 1

spironolactone and cyproterone
with the former historically chosen preferentially as it was believed to have a superior safety profile.

Question 2

Following orchiectomy (+/- vaginoplasty), are anti-androgens necessary ?

Answer 2

most transfeminine patients will not require androgen suppression.

Question 3

How to stop anti-androgen after orchiectomy (+/- vaginoplasty) ?

Answer 3

• The androgen- blocker can be stopped immediately after surgery
• or tapered over the course of 4-6 weeks or more depending on individual factors (e.g., patients with hypertension or renal dysfunction on spironolactone should be tapered).

Question 4

How to initiate anti-androgen vs estrogen (timing)

Answer 4

• There is a lack of consensus on the preferred timing of the initiation of estrogens in relation to an anti-androgen.
• Common approaches have included both the initiation of an anti- androgen (usually 1-3 months) prior to the addition of estrogen, or alternatively, the simultaneous introduction and subsequent titration of both components.

Question 5

In patients over 50 years old who have been on estrogen for several years, doses can change how ?

Answer 5

may be reduced to those administered to post-menopausal cis women (e.g. starting/low dose topical formulations).

Question 6

What to keep in consideration for estrogen therapy in adolescent patients ?

Answer 6

• In adolescent patients, the initiation of estrogen therapy prior to the completion of skeletal growth may lead to an earlier cessation of long bone growth and thus shorter adult height, an effect which would be irreversible.
• This may be a desired effect.
• Complete epiphyseal fusion can occur as early as age 14 and as late as age 19 in AMAB individuals.

Question 7

Name Contraindications estrogen therapy (5)

Answer 7

• Unstable ischemic cardiovascular disease
• Estrogen-dependent cancer
• End stage chronic liver disease
• Psychiatric conditions which limit the ability to provide informed consent
• Hypersensitivity to one of the components of the formulation

Question 8

Describe recommended doses : Spironolactone (oral)
* Starting dose
* Usual dose
* Maximum dose

Answer 8

• Starting dose : 50 mg daily-BID
• Usual dose : 100 mg BID
• Maximum dose : 150 mg BID (rarely required or used. Maximal effect does not necessarily require maximal dosing. Use clinical judgement in selecting optimal individual dosing)

Question 9

Describe recommended doses : Cyproterone (oral)
* Starting dose
* Usual dose
* Maximum dose

Answer 9

• Starting dose : 12.5 mg (1/4 50 mg tab) q2d - daily
• Usual dose : 12.5 mg (1/4 50 mg tab) – 25 mg (1/2 50 mg tab) daily
• Maximum dose : 50 mg daily

Question 10

Name formulaitons of estrogen (4)

Answer 10

• Estradiol (oral)
• Estradiol (transdermal, patch)
• Estradiol (transdermal, gel)
• Estradiol valerate Injectable (IM)

Question 11

Describe recommended doses : Estradiol (oral)
* Starting dose
* Usual dose
* Maximum dose

Answer 11

• Starting dose : 1–2mg daily
• Usual dose : 4mg daily or 2mg bid
• Maximum dose : 6 mg daily or 3 mg BID

Question 12

When and why should Transdermal estradiol be given ? (3)

Answer 12

• seems to be less thrombogenic than oral estradiol
• fewer hepatic side effects
• thus recommended for patients over 40 or with risk factors for cardiovascular, thromboembolic, or liver disease.

Question 13

Name irreversible physical effect of estrogen (1)

Answer 13

Breast growth

Question 14

Physical changes related to androgen blockade and estrogen may take months to appear and are generally considered to be complete after____ on hormone therapy.

Answer 14

2-3 years

Question 15

Does feminizing therapy affect the pitch of the voice in transfeminine patients ?

Answer 15

No

Question 16

Name physical effects of estrogen (11)

Answer 16

• Softening of skin/ decreased oiliness
• Body fat redistribution
• Decreased muscle mass/strength
• Thinned/slowed growth of body/facial hair (omplete removal of facial hair requires electrolysis, laser treatment, or both)
• Scalp hair loss (loss stops, no regrowth)
• Breast growth
• Decreased testicular volume
• Decreased libido
• Decreased spontaneous erections
• Decreased sperm production
• Reduced erectile function

Question 17

Describe : Standard monitoring of a feminizing hormone regimen

Answer 17

• baseline, 3, 6, and 12 months; and yearly thereafter
• creatinine and electrolytes should be checked 4-6 weeks after the initiation or dose increase of spironolactone

Question 18

Dose titration of an anti-androgen and estrogen may be performed how ?

Answer 18

• over the course of 3-6 months or more
• will depend on patient goals, physical response, measured serum hormone levels, and other lab results.

Question 19

What’s the range of suppression of testosterone for patients ?

Answer 19

• For many transfeminine patients, the goal will be
• to achieve the suppression of testosterone into the female range.
• Hormone levels for those seeking a more androgynous appearance may intentionally be mid-range between male and female norms.

Question 20

Serum estradiol levels should also be monitored. Most patients attain considerable feminization at estradiol levels between ____ pmol/L.

Answer 20

200-500

Question 21

True or False
Clinical effects are the goal of therapy, not specific lab values.

Answer 21

Clinical effects are the goal of therapy, not specific lab values. If the sex marker associated with the patient’s health card has not been changed, the reported reference ranges will refer to the sex assigned at birth. Reference ranges vary between laboratories - refer to reference ranges from the specific laboratory (often available online or by request from the lab).

Question 22

Name bloodwork at baseline (10)

Answer 22

• CBC (at baseline for all, and regularly with cyproterone)
• ALT (at baseline for all and regularly with cyproterone, otherwise repeat once at 6-12 months then as needed)
• Creatinine/Lytes (Cr and lytes should be monitored at each visit with spironolactone (including 2-6 weeks after starting), but is only required at baseline and then once between 6-12 months with cyproterone unless risk factors or concerns re: renal disease are present)
• HbA1c or Fasting Glucose
• Lipid profile
• Total Testosterone
• Estradiol
• Prolactin (at least yearly with the use of cyproterone, and more frequently if elevation is noted)
• Other : Hep B and C
• Consider: HIV, syphilis, and other STI screening as indicated, frequency depending on risk

Question 23

What’s the risk of cyproterone (CNS) ?

Answer 23

• Possible increase in Meningioma
• If prolonged use (> 2 years) and higher doses (>10 mg daily)

Question 24

Describe monitoring for patients using cyproterone (particularly at doses> 10 mg for > 2 years)

Answer 24

monitored for signs and symptoms of meningioma including:
* changes in vision
* hearing loss or ringing in the ears
* loss of smell
* headaches
* memory loss
* seizures
* weakness in the arms and legs

No routine screening for meningioma is recommended for asymptomatic patients, regardless of dose/duration

Question 25

In those who present with sx concerning for meningioma, what to do ?

Answer 25

MRI or CT of the brain (and spinal cord if spinal meningioma is suspected) is recommended

Discontinue cyproterone