Masculinizing Hormone Therapy

The cornerstone of hormone therapy for trans masculine patients is testosterone. The goal of treatment is virilization – the development of masculine secondary sexual characteristics.

Quick reference guide for masculinizing hormone therapy:

Download (ENG)
Quick reference guide for primary care providers (ENGLISH VERSION)
Download (FRE)
Aide-mémoire pour professionnels de la santé de première ligne (FRENCH VERSION)

Hormonal agents

Testosterone

In Ontario, options for testosterone administration include injectable and transdermal preparations (patch or gel). Injectable formulations are most commonly used, due to their superior efficacy and affordability. While intramuscular injection (IM) is the most common means of administering parenteral testosterone, subcutaneous (SC) delivery has also been used with clinical efficacy and is very well-tolerated. Proponents describe less discomfort for patients, a decreased rate of injection-site complications, and increased capacity for self-injection. An initial dose reduction of 10-15% can be considered if switching from IM to SC.

Keep in mind

If patients wish to self-inject, it is important to instruct them on the technique for safe injection and sharps disposal. A written step-by-step guide on self-injection for patients is available from Fenway Health

Overview of formulations, recommended doses and costs of testosterone

Formulations Starting/Low Dose Maximum Dose Cost per unit Approx Cost*(4 weeks)
Testosterone enanthatea (IM/SC) 20 - 50 mg q weekly or 40 - 100 mg q 2 weeks 100 mg q weekly or 200 mg q 2 weeks $73.50 per 5 mL vial (each vial contains 200 mg/mL x 5mL = 1000 mg) $14 - $29
Generally covered by ODB with EAP request
Testosterone Cypionate (IM/SC)a $64 per 10 mL vial (each vial contains 100mg/mL x 10mL =1000 mg) $13 - $26
Generally covered by ODB with EAP request
Testosterone (transdermal) Patchb 2.5 – 5 mg daily 5 - 10 mg daily $164/60 x 2.5 mg patches
 $169/30 x 5 mg patches $76.50 - $315
Testosterone Gel 1% (transdermal) 2.5 - 5 g daily (2-4 pumps, equivalent to 25 - 50 mg testosterone) 5 - 10 g daily (4-8 pumps, equivalent to 50 - 100 mg testosterone) $67/30 x 2.5 g sachets
 $110 / 30 x 5 g sachets
 $175 / 2 pump bottlesc Sachets: 
$62 - $205
Bottles: $81 - $32
  • * Price quotes are provided by www.pharmacy.ca
    Note: Testosterone (in all forms) is considered a controlled substance in Canada; prescriptions should be written in accordance with provincial requirements for controlled substances.
  • a) Testosterone enanthate is compounded in sesame oil, and testosterone cypionate is compounded in cottonseed oil; patients with allergy to either of these compounds should use the alternative agent
  • b) Androderm brand, per drug monograph the 12.2 mg patch delivers 2.5 mg/day while the 24.3 mg patch delivers 5 mg per day
  • c) Each pump bottle provides 60 pumps, 1 pump = 1.25 g of gel, equivalent to 12.5 mg of testosterone

Expected effects

What to expect from testosterone

The degree and rate of physical effects is dependent on the dose and route of administration, as well as patient-specific factors such as age, genetics, body habitus and lifestyle.

Desired androgenic effects of testosterone therapy include deepened voice, cessation of menses, clitoral growth, increased muscle mass, and hair growth in androgen dependent areas including facial hair. Breast tissue may lose glandularity, but generally does not lose mass or hemi circumference.1 Typically, patients taking testosterone will experience masculinizing changes over a period of months to years. The timeframe of physiologic changes may be slightly slower with the use of transdermal preparations.

  • 1Futterweit W, Schwartz IS. Histopathology of the breasts of 12 women receiving long-term exogenous androgen therapy. The Mount Sinai journal of medicine 1988;55(4):309-312.

Keep in mind

Testosterone therapy results in both reversible and irreversible masculinization.

Effects and expected time course

Click to view individual expected effects

Risk mitigation

Absolute contraindications

  • Pregnancy or breast feeding
  • Active sex hormone-sensitive cancer (e.g., breast, endometrial)
  • Unstable ischemic cardiovascular disease
  • Poorly controlled psychosis or acute homicidality
  • Psychiatric conditions which limit the ability to provide informed consent
  • Hypersensitivity to one of the components of the formulation

Precautions and Risk mitigation

Pre-existing medical conditions and risk factors may impart increased risks with testosterone administration and should be considered in order to enable individualized discussions with patients regarding the risks and benefits of treatment. Available measures to reduce associated risks should be considered and discussed with patients and if possible, undertaken prior to or concurrently with the initiation of hormone therapy.

Select area of concern below

Neurologic

Risk factors How to minimize risks
Migraines Consider daily migraine prophylaxis, consider transdermal route of administration
Androgen-sensitive epilepsy Refer to neurology

Endocrine

For more information on metabolic effects please refer to the full Guidelines.

Risk factors How to minimize risks
Uncontrolled diabetes Identify and address barriers to optimal glycemic control, refer to dietitian, encourage lifestyle modification, initiate antiglycemic agent(s) per national guidelines, consider endocrinology referral, consider cardiac stress test, consider low dose/slow titration with monitoring
Uncontrolled dyslipidemia Identify and address barriers to optimal lipid control, refer to dietitian, initiate anti-lipemic pharmacologic therapy per national guidelines, consider endocrinology referral, consider cardiac stress test, consider low dose/slow titration with monitoring

Cardiovascular

For more information on cardiovascular disease please refer to the full Guidelines.

Risk factors How to minimize risks
Stable ischemic cardiovascular disease Consider referral to cardiology, ensure optimal medical (including prophylactic anti-platelet agent(s) if indicated per national guidelines) and/or surgical management as indicated, risk factor optimization, consider transdermal route of administration, and/or low dose/slow titration with monitoring
Uncontrolled high blood pressure Identify and address barriers to optimal BP control, initiate antihypertensive(s) as needed, consider cardiac stress test, consider low dose/slow titration with monitoring, consider referral to cardiology

Hepatic

Elevation of liver enzymes may occur with testosterone therapy. For more information on hepatic dysfunction please refer to the full Guidelines.

Risk factor How to minimize risks
Hepatic Dysfunction Dependent on etiology, e.g. minimize alcohol consumption, weight loss in NAFLD, consider referral to hepatology/GI, consider low dose/slow titration with monitoring
Hepatitis C Screen patients who are at risk and treat as per current national guidelines
!

Gynaecologic

For more information on vaginal bleeding and endometrial cancer please refer to the full Guidelines.

Risk factors How to minimize risks
Inter-menstrual bleeding Work up per national guidelines, gynaecology referral as needed
Oligo-/amenorrhea Consider pelvic ultrasound (transvaginal if possible), consider progesterone-induced menstrual bleed prior to testosterone initiation

Hematologic

Risk factors How to minimize risks
Polycythemia Identify etiology and address contributing factors, consider referral to hematology, consider transdermal route of administration, and/or low dose/slow titration with monitoring. More information can be found in the full Guidelines
History of deep vein thrombosis (DVT), pulmonary embolism (PE) or hypercoagulable state Identify and minimize existent risk factors, prophylactic anti-coagulation if indicated per current national guidelines, consider referral to hematology/thrombosis clinic, consider transdermal route of administration, and/or low dose/slow titration with monitoring

Respiratory

Risks/Precautions How to minimize risks
Smoker Encourage and support smoking cessation, consider referral to smoking cessation program/offer NRT and/or bupropion/varenicline, or negotiate a decrease in smoking, consider cardiac stress test. In the presence of additional thrombotic risk factors, consider transdermal route of administration
Chronic respiratory disease that may be worsened by erythrocytosis/polycythemia Consider transdermal route of administration, and/or low dose/slow titration with monitoring. Consider referral to respirology
Severe/uncontrolled sleep apnea Initiate CPAP or oral device, refer to dietitian/ encourage lifestyle changes if overweight, monitor for changes in CPAP pressure requirements. More information can be found in the full Guidelines

Immunologic

More information on HIV in the full Guidelines.

Risk factors How to minimize risks
Autoimmune conditions (e.g. RA, MS, IBD) Consider low dose/slow titration with monitoring in collaboration with any involved specialists
HIV Screen patients who are at risk and treat as per current national guidelines, pay particular attention to CVD and osteoporosis risk reduction, consider use of PrEP in HIV negative patients who are at risk
  • BP: blood pressure; NAFLD: non-alcoholic fatty liver disease; DVT: deep vein thrombosis; PE: pulmonary embolus; CPAP: continuous positive airway pressure; NRT: nicotine replacement therapy; RA: Rheumatoid arthritis; MS: multiple sclerosis; IBD: inflammatory bowel disease

Keep in mind

Denying access to hormones can do much more harm than the possible risks of treatment. With an informed-consent approach (support, information, education and consent) many providers will initiate hormones with individuals with higher risk profiles when it increases their quality of life/chance of survival greatly.

Monitoring and dose titration strategies

Standard monitoring of testosterone administration should be employed at baseline, and at 3, 6, and 12 months following initiation. Some clinicians prefer to see patients monthly until an effective dose is established. Follow up visits should include a functional inquiry, targeted physical exam, blood work, and health promotion/disease prevention counselling as indicated.

Titration of doses will generally occur in the early phases of treatment. For example, with injectable testosterone, a starting dose of 30mg injected weekly could be increased by 10-20mg every 4-6 weeks. Speed of titration will depend on lab results, patient goals, response, and side effects. There may be utility in varying the timing of blood work to gather information regarding serum levels throughout the cycle (peak, mid-cycle, and trough), especially if a patient is reporting cyclic symptoms. Some patients will intentionally seek testosterone levels mid-way between the male and female range. For patients seeking maximum masculinization, the target dose will bring the testosterone level into the physiologic male range. Once the midpoint of the male reference range is attained, additional benefit is questionable. Supraphysiologic levels should be avoided due to the increased risk of adverse events and side effects, as well the potential for the aromatization of excess testosterone into estrogen. Dose reduction is warranted if supraphysiologic doses are measured at mid-cycle or trough. There may be some irregular bleeding or spotting in the first few months of treatment. However, once sustained menstrual cessation is achieved, any vaginal bleeding without explanation (e.g. missed dose(s) or lowered dose of testosterone) warrants a full workup for endometrial hyperplasia/cancer.

Keep in mind

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

Hormone Monitoring Summary

See tables below for a summary of recommended monitoring for transmasculine patients at baseline, 3, 6, and 12 months after starting therapy

Note: Some providers prefer to see patients monthly until an effective dose is established.

Baseline (See Planning Period Checklist for complete list) Month 3 Month 6 Month 12c Yearly
Review Please see the Appendix F and G of the Guidelines for a Preventive Care Checklist for transmasculine Patients and accompaniment.
Exam
/
Investigation
  • Blood pressure
  • Weight
Immunizations
  • Consider HPV, Hep B, C, and routine vaccinations as indicated

Summary of recommended labs

Note: In this table, lighter grey checkmarks indicate parameters that are measured under particular circumstances.

Baseline Month 3 Month 6 Month 12c Yearly According to guidelines for cis patients, or provider discretion
CBCa ✔ ✔ ✔ ✔ ✔
ALT ✔ ✔d ✔
HbA1c or Fasting Glucose ✔ ✔d ✔
Lipid profile ✔ ✔d ✔
Total testosterone ✔ ✔ ✔ ✔ ✔
LHb ✔ ✔ ✔
Other Hep B,C
Pregnancy test
(before first dose)
Consider HIV, syphilis, and other STI screening as indicated, frequency depending on risk
  • NB Individual parameters should be considered more frequently if concerns identified or existing risk factors are present
    • a) Male reference ranges should be used for Hb/Hct (lower limit of female range can be used if menstruating)
    • b) Post-gonadectomy only: elevated LH may have implications regarding bone mineral density (See full Guidelines for Osteoporosis and BMD Screening)
    • c) During first year of treatment only
    • d) Once at either 6- or 12-month mark

Long-term preventive care

Transmasculine patients maintained on masculinizing hormone therapy have unique preventive care needs and recommendations.

Long-term follow-up care of transmasculine patients on masculinizing hormone therapy should involve (at least) annual preventive care visits. An Adaptive Preventive Care Checklist with accompanying explanations for trans-specific recommendations can be accessed below.

  • Download
    Preventive care checklist for transmasculine patients
  • Download
    Accompaniment to preventive care checklist for transmasculine patients

Ensuring patient comfort in clinical encounters

Physical examinations that involve intimate body parts are discomforting to anyone. However, it is important to consider how trans patients may need a slightly different approach in some areas of primary care practice: tasks like disease prevention and screening, which may also require us to think differently.

It is important to reflect on approaches to clinical encounters with trans patients (e.g., consider offering to use a side- lying rather than lithotomy position when doing a Pap test with transmasculine individuals) to provide a more comfortable and gender-affirming experience.

When interacting with trans patients, asking what’s most comfortable for them is fundamental—what one patient prefers is not always transferable to the next.

Provide care based on organs present

It is best to base routine screening on the presence or absence of body parts. Refrain from calling body parts ‘male’ or ‘female’. Instead use non-gendered terms or ask the patient what they prefer to call their body parts. Organs present should receive routine preventive care.

Click on one of the tabs to find out about routine care and screening suggestions

Osteoporosis and Bone Mineral Density Screening

Indications for BMD screening

  • Patients over 65 years old
  • Patients 50-64 years old at higher risk for osteoporosis (e.g. smoking history, HIV+, high alcohol intake, body weight under 60 kg)
  • Consider before 50 years old:
    • Certain high-risk conditions such as hyperparathyroidism or malabsorption syndrome.
    • Patients who have undergone oophorectomy and have been on low-dose or no exogenous testosterone for any significant length of time (>2 years).
    • Patients post-oophorectomy with elevated LH levels.
    • Patients who have been on a GnRH analogue for a significant length of time (2 years) without co-administration of exogenous testosterone.
  • All transmasculine patients should ensure a daily intake of 1000 IU Vitamin D and 1200mg of Calcium (total of diet + supplements). Gradual weight-bearing exercises should also be encouraged (this could include walking and low-impact aerobic exercise).

Keep in mind:

  • There are no studies to guide the interpretation of BMD results and fracture risk in trans people, and whether to use sex assigned at birth or affirmed gender. One option is to interpret results in comparison to both men and women.
  • Frequency of BMD screening will depend on the results of the initial scan

Breast/Chest Cancer Screening

Without top surgery/chest reconstruction:

Transmasculine patients who have not undergone chest reconstruction should follow guidelines for screening mammography as for cis women. As with cis women, some transmasculine patients may be at higher risk based on factors such as genetic mutations, family history and prior radiation exposure.
Following top surgery/chest reconstruction:

Transmasculine patients who have undergone chest reconstruction likely experience significant risk reduction as there is much less tissue present, however residual breast tissue does remain, particularly in the axillary regions. Mammography may not be possible following chest reconstruction. Ultrasound or MRI may be considered as alternate modalities for screening in patients with significant risk factors (or if an abnormality is detected on exam).
Keep in mind the following:
  • Some transmasculine patients may prefer to use the term chest over breast(s).
  • Transmasculine patients who have a male gender marker on their health card, will not be able to self-refer to the Ontario Breast Screening Program. A requisition is required in this case.

Recommendations for patients at average risk of developing breast cancer are visualized in the image below

Diagrammatic flow chart representation of breast/chest screening recommendations for patients on hormone therapy at average risk of developing breast cancer. If client has not had chest reconstruction/top surgery/mastectomy then the guidelines for cis women should be followed: If they are aged between 40-49, then you should discuss individual risks of breast/chest cancer & benefits and risks of mammography. If they are aged between 50-74 years, then a mammogram every two years is recommended. If client has had reconstruction/top surgery/mastectomy then no routine screening investigations are needed, in the absence of significant risk factors.

Colon cancer screening

Screening guidelines for transmasculine patients are no different than for cis populations. Please follow your local screening guidelines (e.g. Cancer Care Ontario for Ontario guidelines).

Cervical cancer screening

Use the diagram below to find out what type of cervical cancer screening is recommended.

Diagrammatic flow chart representation of cervical screening recommendations for patients on hormone therapy. If the client does not have a cervix, screening generally is not necessary - follow guidelines for cis women. Note: Total hysterectomy (removal of uterus and cervix) is performed prior to closure/removal of the vagina (as is commonly done with metoidioplasty and phalloplasty). Such patients would be unable to undergo vault/cuff smear. If client has a cervix and is sexually active (aged 21-69) then screening every three years with a Pap test is recommended. If client has a cervix and is not sexually active then screening is not necessasry.

Keep in mind the following:

  • Gauge your patient’s comfort with the exam. Some, but not all, transmasculine patients may feel uncomfortable with the idea of penetration and may feel their gender is undermined by the function of the speculum. It may be helpful to explain why a speculum is needed.
  • Ask if the patient has had a Pap test before, or whether they have had vaginally penetrative/frontal sex. If the patient has no experience with penetration, it may be helpful to know this in advance and to suggest that they try penetration at home first using a small toy, fingers or a speculum. This may help make the screening process less confusing or disturbing. Some transmasculine patients may be willing to try this, while others will not.
  • Some transmasculine patients who are taking testosterone will have fewer secretions, so using lubrication and warm water can be helpful in speculum insertion. Barring contraindications, topical 2% lidocaine jelly may be applied vaginally 5-10 min prior to the procedure in those who find speculum examination painful due to atrophic changes.
  • Testosterone can cause cervical cell changes that may make the sample more difficult to read. If the patient is on testosterone, note this on the requisition.
  • Inadequate samples are common in patients on testosterone.1 The use of both brush and broom may increase yield in patients with atrophic changes.2
  • HPV vaccine should be offered to patients under age 45.
  1. Peitzmeier, Sarah M., MSPH|Khullar, Karishma, BS|Reisner, Sari L., ScD, MA|Potter,Jennifer, M.D. Pap Test Use Is Lower Among Female-to-Male Patients Than Non-Transgender Women. Am J Prev Med 2014;47(6):808-812.
  2. Davis-Devine S, Day SJ, Anderson A, French A, Madison-Henness D, Mohar N, et al. Collection of the BD SurePath Pap Test with a broom device plus endocervical brush improves disease detection when compared to the broom device alone or the spatula plus endocervical brush combination. CytoJournal. 2008; 6:4.
  3. Potter J, Peitzmeier SM, Bernstein I, Reisner SL, Alizaga NM, Agénor M, et al. Cervical Cancer Screening for Patients on the Female-to-Male Spectrum: a Narrative Review and Guide for Clinicians. Journal of General Internal Medicine 2015;30(12):1857-1864.

Ovarian cancer

Analogous to concerns of an increased risk of ovarian cancer in cis women with elevated androgen levels, it has been postulated that testosterone therapy in transmasculine patients may increase risk. There have been a few cases of ovarian cancer in transgender men. Overall there is no evidence to suggest an increased risk of ovarian cancer in transmasculine patients on testosterone, and thus no cause to perform oophorectomy in transmasculine patients solely for purposes of primary prevention.

Hormone Planning Period

Feminizing Hormone Therapy