top of page

Overview of Estrogen-Based GAHT

The goal of estrogen-based GAHT is to reduce the endogenous effects of testosterone and to induce feminine secondary sex characteristics in keeping with the patient’s individual goals, as determined by their experience of gender incongruence and associated dysphoria, if present.

 

Physiologically, this requires the suppression of endogenous androgens and the addition of estrogen. This treatment results in both reversible and irreversible feminization. General effects such as reduction in muscle mass, reduction of body and (to a lesser extent) facial hair, and changes in skin as well as sweat and odour patterns are reversible.

 

Changes in facial and body subcutaneous fat distribution are generally considered reversible effects but to some degree may not be. Sexual and gonadal effects, including changes in libido and reduction in erectile function, are generally

Effects and expected time course of estrogen-based hormones .png

considered reversible, while reduced testicular and prostatic size, sperm count reduction and the resulting impact on fertility may be irreversible. For a more detailed discussion of the impact of estrogen-based GAHT on reproductive health, please see Part 6: Sexual Health and Reproduction.

 

Breast development is considered irreversible and would require surgical intervention to reverse. 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 therefore shorter adult height—an effect that would be irreversible. The degree and rate of physical effects are also dependent on the dose administered, as well as patient-specific factors such as age, ethnicity, genetics, body habitus and lifestyle. The effects of estrogen-based GAHT and their expected time courses are shown below.

Anti-Androgens

Treatment with physiologic doses of estrogen alone is not usually sufficient to suppress testosterone levels into the physiologic female range in patients who have not undergone gonadectomy. Due to the potential for adverse effects with higher doses of estrogen, androgen-suppressing agents are used as part of a GAHT regimen in patients with gonads.

 

The anti-androgens most commonly used are spironolactone and cyproterone. Spironolactone is a potassium-sparing diuretic, which acts as an anti-androgen at higher doses through direct blockade of peripheral androgen receptors. It also exerts secondary suppressive effects on androgen synthesis and has weak estrogenic and progestational activity. Given that its primary mechanism of action is at the receptor level, it will not always cause a significant change in blood testosterone levels. As a result, effectiveness should be evaluated by a patient’s reported response (i.e., absence of spontaneous arousal, slowing of facial and body hair growth, skin changes) rather than serum levels.

 

Cyproterone is a synthetic steroid with progestin-like activity. Like spironolactone, it exerts anti-androgenic effects by binding to androgen receptors. In addition, its progestational activity exerts negative feedback on testosterone production through a reduction in gonadotropins. Anecdotally, cyproterone has been shown to be a more potent anti-androgen than spironolactone, with more rapid effects and a more marked suppression of libido and erectile function.

 

In the absence of sufficient data to guide a preferential choice of one anti-androgen over another, the decision can be made individually for each patient based on medical history and preference regarding risk and side effect profiles. Both spironolactone and cyproterone are covered by the NB Drug Plan with premiums based on annual income  and by the The New Brunswick Prescription Drug Program (NBPDP) depending on patient eligibility. For more information, see NIHB Program.

SPIRONOLACTONE

Drug Effects

  • Breast growth*

  • Decreased androgenic alopecia

  • Decreased fertility**

  • Reduced erectile function** 

  • Reduced prostatic and testicular volume**

  • Slowed growth of facial/body hair

 

* Irreversible

** May be irreversible

Side Effects

  • Gastrointestinal side effects 

  • Hyperkalemia

  • Hypotension

  • Orthostasis, dizziness

  • Polyuria

  • Polydipsia

  • Rash 

  • Renal impairment

  • Risk of dehydration 

  • Somnolence         

Contraindications

  • Addison’s disease or other conditions associated with hyperkalemia (type IV tubular acidosis) 

  • Hyperkalemia

  • Renal insufficiency

 

Avoid concomitant use of:

  • ACE Inhibitors, 

  • ARBs, 

  • Other potassium-sparing diuretics (if concomitant use is not avoidable, use with caution; consider low dose, slow titration and frequent monitoring due to the high risk of hyperkalemia) 

  • Trimethoprim-sulfamethoxazole potassium supplements eplerenone, heparin, and low molecular weight heparin.

ACE: angiotensin converting enzyme

ARB: angiotensin II receptor blocker

CBC: complete blood count

VTE: venous thromboembolism

Anti-Androgens Dosage

Generally, spironolactone can be started at 50 mg once daily, and increased every 2–4 weeks or more barring negative effects. Doses can be divided twice daily, or given once daily in the morning (for those who experience problematic nocturia) or at night (for those who have concerns around daytime bathroom safety). Total daily doses up to 300 mg/ day have been used but are rarely required.

                    

Cyproterone can be initiated at 12.5 mg and increased by 12.5 mg every 2–4 or more weeks (to a rare maximum of 50 mg) if required. Lower doses and/or less frequent dosing (e.g., one-quarter of a 25 mg tablet twice weekly, one-eighth of a 25 mg tablet every other day, etc.) have been used with success for patients who wish to maintain sexual function or minimize other side effects.

                    

Time intervals for dose titration should take into consideration existing medical conditions, bloodwork results and individual transition-related goals. If an adequate response is not achieved with maximum doses of the initially chosen agent, or if side effects prohibit titration to adequate effect, we suggest initiating a trial of the alternative agent (in the absence of contraindications). When discontinuing spironolactone, consider a taper in patients with hypertension or renal dysfunction, with monitoring of blood pressure and volume status. The chart below shows the starting/low, customary and maximum doses for spironolactone and cyproterone.

Spironolactone (oral)

Starting/Low Dose

  • 50mg daily-bid

Usual Dose

  • 100 mg bid

Maximum Dose

  • 150mg bid*

Pricing 

  • 30 x 25mg - $12.97

  • $48.42-145.26 every 4 weeks

*Rarely required or used. Maximal effect does not necessarily require maximal dosing. Use clinical judgment in selecting optimal individual dosing.

Price quotes provided by APSI, accurate as of August 2022 and represent the price of the generic brand of medication unless otherwise indicated (ranging from low dose to maximum dose). Prices reflect the actual customer cost for purchase within New Brunswick, including a dispensing fee, and not including Medicare or a drug plan.           

If contraindications exist or if intolerance is a concern for both spironolactone and cyproterone, GnRH analogues (leuprolide/“Lupron” or busrelin/“Suprefact”) may be considered. GnRH analogues flood the pituitary gland’s GnRH receptors, leading to a downregulation of the response to endogenous GnRH and sustained suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release. GnRH analogues are commonly used for pubertal suppression in youth and have also been used in adults undergoing GAHT.

 

Drawbacks include high cost, repeat (often painful) injections or frequent nasal spray dosing, and possible side-effects, including headache, mood changes and weight gain. It should be noted that the administration of a GnRH analogue in the absence of exogenous hormone use, for a significant amount of time (i.e., > 2 years), can decrease bone mineral density. If providers lack experience with the use of GnRH analogues, Sherbourne Health recommends consultation or communication with an endocrinologist or another experienced provider prior to initiation.

 

If the administration of anti-androgens is problematic, another option is the removal of the major source of endogenous testosterone (i.e., orchiectomy). For patients who are unable to access or are not seeking vaginoplasty (during which orchiectomy is routinely performed), orchiectomy alone is a choice that may be considered and is covered under New Brunswick Medicare (for more information see Part 5: Gender-Affirming Surgery).

 

For the vast majority of patients who have undergone gonadectomy, androgen suppression will no longer be required. The androgen-blocker can be stopped immediately after surgery or tapered over the course of 4–6 weeks or more post-operatively. In some cases, the effects of anti-androgens may be sought without the additional effects of estrogen, or when estrogen is contraindicated.

 

In addition to potential hot flashes, low mood, and fatigue, there may be a loss of bone mineral density, akin to that demonstrated in cisgender men who have undergone long-term androgen blockade without hormone replacement for the treatment of prostate cancer. This treatment may, however, be considered in some circumstances, following detailed discussion with the patient, and with preventive measures and monitoring for bone loss in place. Periodic bone mineral density testing for those on prolonged monotherapy with an anti-androgen can be used to identify any concerning loss of bone density. 

 

The table below displays the monitoring parameters for both spironolactone and cyproterone. Note that additional parameters are required once estrogen is initiated (see Estrogen).

Recommended parameters for monitoring anti-androgen GAHT    

Screen Shot 2022-10-29 at 8.15.42 PM.png

A. If not done in the preceding 3 months 

 

B. Breast inspection at baseline with attention to Tanner stage (+/- measurement), for patients who may have interest in breast augmentation.

 

C. Red blood cell parameters can be expected to decrease with androgen blockade, female reference ranges for lower limits of normal should be used

 

D. Necessary only if risks/concerns identified
                                            

Note: Additional parameters required as per guidelines with estrogen; pre-existing conditions or risk factors may require earlier/more frequent monitoring of specific parameters.

Estrogen

Estrogens act directly on estrogen receptors to initiate feminization. The degree and rate of physical effects are largely dependent on patient-specific factors such as age, genetics and body habitus, and to some extent the dose and route used, selected according to a patient’s specific goals and risk profile. There is a lack of consensus among clinicians 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 prior (usually 1–3 months) to the addition of estrogen, or alternatively, the simultaneous introduction and subsequent titration of both components.

 

When deciding on the relative timing of anti-androgen and estrogen introduction, take into consideration that:

  • The effects of anti-androgens are generally considered reversible, so the initiation of an anti-androgen first may be a preferred first step for patients seeking to explore the impact of subtle bodily changes before proceeding with estrogen, or for those wishing to take a gradual approach to medical transition;

  • Staggering the initiation of an anti-androgen and estrogen allows for more readily identifying the problematic agent in the case of unusual side effects or drug allergy;

  • In the absence of estrogen replacement, some patients may experience hot flashes, low mood, and/or fatigue; and

  • There is weak evidence (one small study) suggesting that spironolactone used alone may prematurely inhibit breast development. Whether other anti-androgens may have a similar impact is unknown.

 

Several forms and routes of estrogen have been used for GAHT. The most common form used is oral 17-β estradiol (Estrace) - 17-β estradiol, whether in tablet or topical form, is a bio-identical hormone, structurally identical to estrogen made by the ovary in humans. Premarin, an estrogen derived from pregnant mare urine, is not bio-identical.

 

Oral formulations are subject to first pass gastrointestinal (GI) and liver metabolism which, according to the “first-pass hypothesis,” contribute to negative hepatic and prothrombotic effects. Sublingual, transdermal and injectable routes all bypass this stage during which much estradiol is oxidized to the less potent estrone.

                    

The administration of estrogen via the sublingual route has gained interest in recent years given its accessibility (oral formulations of micronized estradiol can be dissolved under the tongue), affordability (compared to the transdermal route) and the proposed benefits of bypassing first pass metabolism.

                    

Similar to the sublingual route, injectable estrogens bypass first pass metabolism and result in higher peaks and increased periodicity over oral forms. Injectable estrogen (in the form of compounded estradiol valerate) is available in Moncton; however, due to its high peaks and lows is not typically recommended. Moreover, injectable estrogen can have significant impacts on mental health and is difficult to find a therapeutic dose. However, PCP may still come into contact with a patient who is using  IM estradiol valerate. PCPs should inform patients of other estrogen-based hormone regimes as if and when necessary.

 

If a patient is continuing to use IM estradiol valerate it is important to instruct them on the technique for safe injection and sharps disposal. Directly observing a patient self-inject is helpful for the correction of any problems with technique and to reassure patients that they are injecting correctly. Ideally patients would complete their first hormone administration in a PCP’s office. A written step-by-step guide on self-injection for patients is here. Additionally, it may be helpful to have patients record the injection training on their phone to refer to after.         

 

Transdermal estradiol bypasses first pass metabolism, results in relatively steady serum levels and seems to have the best overall safety profile. It is most commonly administered in the form of the estradiol patch (“Estradot”), which is available from most pharmacies in New Brunswick but is unfortunately more expensive than oral forms. While it is often covered by private drug insurance, it is only covered by the NB drug plan in rare circumstances, such as a patient having the inability to swallow. 

                

Other transdermal options include creams and gels. Estradiol creams are only available via compounding. Gel is available in a product formulated for the treatment of menopausal cis women (“Estragel”), however the area of skin needed for absorption of the gel is quite large, even for low/starting doses, so it is not a first choice for most trans patients. Cream and gel formulations may be effective for some transfeminine patients, but physiologic estrogen levels may be difficult to achieve in others. Again, these transdermal forms are expensive and not covered by the NB Drug Plan, but may be fully or partially covered by private drug plans. Note that specific details and dosing of compounded formulations should be discussed with the compounding pharmacist.

                    

Following gonadectomy, most patients will not need androgen suppression; however, ongoing estrogen supplementation is generally needed to preserve bone mineral density. Reducing estrogen dosing is not required post-operatively, but some patients may find that a lower dose suffices to maintain desired effects in the absence of any endogenous testosterone. Consideration should be given to bone mineral density in agonadal patients on low dose estrogen.

Estradiol (oral)

Starting/Low Dose

  • 1-2mg daily

Usual Dose

  • 4mg daily or 2mg bid

Maximum Dose

  • 6mg daily or 3mg bid

Pricing 

  • 30 x 0.5mg - $14.40 / $26.88-161.28 every 4 weeks

  • 30 x 1.0mg - $18.50 / $17.27-103.60 every 4 weeks

The common doses of progestins are micronized bio-identical progesterone “Prometrium” 100–200 mg daily; or medroxyprogesterone acetate/”Provera” 5–20 mg daily. Risks are likely lower with micronized progesterone than with medroxyprogesterone, so the former is chosen preferentially by most clinicians. In addition, the former may be better tolerated and have a more favourable impact on the lipid profile than medroxyprogesterone. Injected depo-medroxyprogesterone acetate “Depo-Provera” is seldom used in transfeminine patients. If a progestin is prescribed, some clinicians advise limiting the treatment duration to a maximum of two to three years, or the use of cyclical dosing (i.e., administered 10 days per month).

Progestins    

With the exception of cyproterone, the use of progestins in patients continues to be controversial. Progestins have a suppressive effect on LH and therefore on testosterone production, and have at times been used as part of estrogen-based hormone regimens for patients. There have also been anecdotal reports of improved breast and/or areolar development, mood, sleep and libido with the use of progestins. However, a clear impact has yet to be demonstrated.

                            

In addition to weight gain and edema, depression is an often-cited side effect of progestins. Anecdotally, some patients may experience a favourable impact on mood, while others may experience negative effects. Some protocols have suggested the adjunctive use of progestins when traditional treatments don’t achieve adequate androgen suppression, while others suggest a trial of a progestin as an option for patients with low libido.

                    

Due to the lack of research and the potential risks of progestin therapy Sherbourne Health does not currently recommend the routine use of progestins. However, if patients request progestin treatment, either in hopes of attaining anecdotal benefits, or due to a desire to more closely reflect the hormonal milieu of cis women they should be provided with all available information about the expectations and risks of progestin.             

       

The common doses of progestins are micronized bio-identical progesterone “Prometrium” 100–200 mg daily; or medroxyprogesterone acetate/”Provera” 5–20 mg daily. Risks are likely lower with micronized progesterone than with medroxyprogesterone, so the former is chosen preferentially by most clinicians. In addition, the former may be better tolerated and have a more favourable impact on the lipid profile than medroxyprogesterone. Injected depo-medroxyprogesterone acetate “Depo-Provera” is seldom used in transfeminine patients. If a progestin is prescribed, some clinicians advise limiting the treatment duration to a maximum of two to three years, or the use of cyclical dosing (i.e., administered 10 days per month).

Monitoring and Dose Adjustments (Estrogen-Based GAHT)

Standard monitoring of a estrogen-based regimen should be employed at baseline, three months, six months and one year (additionally, creatinine and electrolytes should be checked between four and six weeks following initiation of spironolactone). Some providers prefer to see patients monthly until an effective dose is established. Follow-up visits should include a functional inquiry, targeted physical exam, bloodwork and health promotion/disease prevention counselling as indicated. 

            

Functional inquiry should include subjective positive or negative impacts on mental health as well as any noted physiologic changes. It may be helpful to remind patients that changes related to androgen blockade and estrogen administration may take months to years for full effect.

                    

The first changes will likely be loss of spontaneous and morning arousal. Breast development, skin and hair changes, and fat redistribution take longer. Some patients may experience a small amount of physiologic galactorrhea early in the course of treatment. If galactorrhea is from more than one duct or bilateral, and non-bloody, no further workup is warranted.

                    

Generally, physical changes are considered to be complete after 2–3 years on GAHT. Periodically, the clinician should counsel around monitoring for signs and symptoms of VTE, particularly in those at increased risk. Patients should be periodically reminded about the importance of adequate calcium and vitamin D intake. Examination should be focused and minimally include blood pressure and weight. 

 

Blood work should be completed according to the table below, with more frequent monitoring as deemed necessary if concerns are identified. 

Recommended blood work for monitoring estrogen-based GAHT            

In this table, smaller and lighter grey “x”s indicate parameters that are measured under particular circumstances.

Screen Shot 2022-10-29 at 7.52.01 PM.png

A. At baseline for all, and regularly with cyproterone, for Hb/Hct use female reference for lower limit of normal and male reference for upper limit of normal

B. Baseline for all and regularly with cyproterone, otherwise repeat once at 6–12 months then as needed

C. Cr, lytes, should be monitored at each visit with spironolactone, 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, use male reference range for upper limit of normal for Cr

D. Prolactin should be monitored at least yearly with the use of cyproterone, and more frequently if elevation is noted

E. During first year of treatment only                

                                         

Note: Individual parameters should be considered more frequently if concerns are identified or existing risk factors are present.

 

Dose titration of anti-androgen and estrogen may be performed over the course of 3–6 months or more, and will depend on patient goals, physical response, measured serum hormone levels and other lab results. A common titration might look like:            

  • Initiate therapy with 1 mg oral estradiol and 50 mg of spironolactone daily;    

  • Check creatinine and electrolytes at one month and, barring any concerns, increase estradiol to 2 mg and spironolactone to 50 mg twice daily;            

  • Following three-month blood work and check-in, increase estradiol to 3 mg daily and spironolactone to 75 mg twice daily; and                

  • Continue titration as needed until maintenance dose is achieved.             

 

Titration schedules vary between clinicians and can be tailored to individual patient needs and variables. Some patients may be eager to begin maximal therapy, but there is some evidence to suggest that excessive estrogenic action may limit breast development, and that the estrogen-receptor agonist activity of spironolactone may contribute to this effect. The evidence is considered weak, however it suggests potential benefits to a slow upward titration. These factors can be discussed with patients in order to facilitate collaborative and informed decision making.    

        

Hormone levels for those seeking a more androgynous appearance may intentionally be mid-range between male and female norms. For many patients, the goal will be to achieve the suppression of testosterone into the female range. Be mindful that patients may experience clinically relevant results without total suppression of testosterone due to peripheral androgen blockade, which is not measured.        

        

In the vast majority of cases, the measurement of total testosterone (rather than both total and free) is adequate to assess the degree of androgen suppression. Measurements and calculated estimates of free testosterone are imprecise and generally don’t add value. In rare cases, the calculation of free or bioavailable testosterone may be helpful for fine-tuning hormone regimens. Again, it is important to keep in mind that clinical effects are the goal of therapy, not specific lab values. 

 

In cases where there are very high estradiol levels reported, reviewing the dose (including use of estrogens without a prescription) and route (i.e., oral versus sublingual) with the patient may be helpful in elucidating the cause.

 

For those on injectable estrogen, levels taken at peak in the cycle may be expected to exceed recommended targets. When monitoring injectable estrogen, most guidelines recommend checking serum levels at mid-cycle, while some clinicians prefer to measure at trough (i.e., just before the next injection is due). The latter adds convenience for patients who prefer to come into the clinic for their injections. There may also 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 (e.g., hot flashes, headaches, fatigue). In such cases, wide fluctuations should prompt consideration of increased frequency of injections or a route with less periodicity.        

        

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. As reference ranges vary between laboratories, it is important to be able to refer to reference ranges for the affirmed gender from the specific laboratory. These can often be found on laboratory websites or can be obtained by request from the lab.    

    

Ideally, labs would be able to report reference ranges in a patient’s affirmed gender, regardless of their health card sex marker, or to report both male and female reference ranges with a patient’s results. There are currently logistical and systems barriers to this practice in New Brunswick labs, though efforts are underway to make improvements in laboratories’ direct service to trans patients as well as amendments to reference range reporting. It is advised to indicate AMAB or AFAB to reduce likelihood of sample rejection.

Limitations to Estrogen-based GAHT       

In the vast majority of cases, hormone levels in the female range can be achieved fairly readily if that is the goal. Yet the physiologic results in transfeminine patients may not meet a patient’s hopes and expectations forestrogen-based GAHT, and some may experience ongoing dysphoria or dissatisfaction. These limitations to estrogen-based GAHT should be reviewed with patients before initiation to minimize disappointment from unachievable expectations.

                                                            

Estrogen-based GAHT does not affect the pitch of the voice in patients. Some patients may benefit from voice therapy with a qualified and supportive speech and language therapist who can work with the patient to modify their vocal characteristics. Currently  speech and language therapist services are not covered in NB for transition-related purposes. A variety of surgical techniques have also been used to feminize the voice by altering the vocal cords. These procedures are also not covered by Medicare and carry risks for vocal and other complications, though some patients may benefit from these procedures if vocal therapy has not produced satisfactory changes. For more information about SLP services in NB go here.

                                                            

Although estrogen-based GAHT slows the rate of growth of hair on the face and neck, it does not eliminate it. Plucking, waxing or depilatory chemicals are temporary measures, therefore many patients will seek permanent hair reduction by laser hair removal or electrolysis. Both of these techniques can be painful, require multiple sessions and may require lifelong treatment for sustained effect. Unfortunately, these procedures are not covered by Medicare. It should be noted that results can be directly impacted by whether the patient’s hair has begun to turn grey.

 

Additionally, estrogen-based GAHT does not affect the underlying bone structure of the face. Some softening of the facial features (possibly through fat redistribution) is anecdotally reported by patients. Some patients may desire facial feminization surgery (FFS), however this procedure is not covered by Medicare.

 

Breast growth is an aspect of estrogen-based GAHT that is very important to many patients. Unfortunately, many patients will be dissatisfied with their degree of breast development. The extent to which the degree of testosterone suppression may affect breast development is unknown. Research to date examining factors impacting breast development in patients is scarce and of low quality. More research is needed to guide recommendations in regards to this aspect of estrogen-based GAHT. Unfortunately, Medicare does not cover augmentation mammoplasty.

There is little information to guide recommendations for the initiation or maintenance of estrogen-based hormone regimens in aging patients. Unique considerations in older populations include changes in endogenous hormone levels, physiologic changes that may affect response to medications, a higher burden of existing medical conditions, and multiple pre-existing medications leading to the increased potential for drug interactions.

                    

It is not uncommon for patients to seek to initiate GAHT at older ages, though estrogen-based effects may be slower and more subtle for those initiating therapy at an advanced age. There is no reason to withhold GAHT from aging or older patients simply due to age. For some older patients who have had to delay transition until later in life, maximizing estrogen-based effects may take precedence over concerns about risk. For such patients, an “active period” of treatment with doses used for younger patients may be considered following an informed consent approach.

                    

For patients over 50, it is reasonable to mimic physiologic hormone levels in menopausal cis women, which can usually be attained with estrogen doses typically administered to post-menopausal cis women, e.g., starting/low-dose topical formulations. For those with gonads, required anti-androgen doses may also be lower due to age-related decreases in serum testosterone.

                    

The preferential use of spironolactone in older transfeminine patients (with healthy renal function) has been suggested by Sherbourne Health given the possible increased thromboembolic risk associated with cyproterone. 

            

For those over age 50 who have been on GAHT for some time, some guidelines suggest considering complete discontinuation of GAHT. However, those without gonads will likely experience symptoms akin to menopause along with potential loss of bone mineral density, and those with gonads may experience a return of virilization. As with all patients, decisions about GAHT at an advanced age should be individualized following a thorough discussion of risks and benefits.

+.png
-.png
+.png
-.png

Providers may have concerns about the safety of estrogen, particularly with respect to cardiovascular/VTE events and malignancies. As more evidence emerges on modern estrogen-based GAHT, fears of a significant negative impact on morbidity and mortality are being decreased. 

                    

Pre-existing medical conditions and risk factors may increase risks with estrogen administration, and should be considered to enable individualized discussions with patients regarding their unique 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 GAHT. In some cases, patients may wish to begin GAHT in the setting of ongoing increased risk, i.e., immitigable risk or having declined measures for risk mitigation. In these situations, a careful informed consent process should be undertaken which takes into consideration individual capacity to make an informed decision, the severity of potential harms from treatment, and the harms that may result from not pursuing treatment.

                    

When necessary, the initiation of estrogen-based GAHT should ideally be done in collaboration with relevant specialists who may already be involved in a patient’s care. In some cases, a new referral may be helpful in informing decisions about risks and their mitigation. However, efforts should be taken to ensure that this does not cause undue delay. If accessibility to a specialist is limited, an e-consult can be both timely and beneficial. 

+.png
-.png

The long-term follow-up of patients on testosterone-based GAHT should involve (at least) annual preventive care visits. Preventive Care Checklists© endorsed by the College of Family Physicians of Canada exist for cisgender patients; however, the use of these forms for 2STIGD patients is awkward, unaffirming, and can lead to missed elements important in their comprehensive primary care. 2SQTP-NB/P2SQT-NB has assembled recommendations from Sherbourne Health and Rainbow Health into an adapted Preventive Care Checklist for the ongoing primary care of patients on testosterone-based hormone therapy. The use of these gender-specific forms assumes familiarity with the standard forms and their explanations. The recommendations represent an effort to incorporate expert opinion, relevant research on cisgender populations and limited gender-specific evidence, with standard national and provincial primary care practices.

Precautions with estrogen-based GAHT and minimizing associated risks

  • Start low dose, titrate slowly in collaboration with any involved specialists

ACEs: angiotensin converting enzyme inhibitors; 

ARBs: angiotensin receptor blockers; 

ASA: acetylsalicylic acid;

BP: blood pressure; 

DVT: deep vein thrombosis; 

GI: gastroenterology; 

IBD: inflammatory bowel disease; 

MS: multiple sclerosis; 

NAFLD: non-alcoholic fatty liver disease; 

NRT: nicotine replacement therapy; 

PE: pulmonary embolism; 

RA: rheumatoid arthritis

For more information on the specific conditions associated with estrogen-based GAHT, risk mitigation, and long-term preventive care, see Sherbourne’s guidelines for gender-affirming primary care with trans and non-binary patients. These guidelines include information and research on the following:

  • Breast cancer

  • Cardiovascular disease and related metabolic risk factors

  • Human immunodeficiency virus (HIV) 

  • Hyperprolactinemia/prolactinoma

  • Liver and gallbladder

  • Osteoporosis and bone mineral density screening

  • Prostate cancer                    

  • Seizure disorders and anticonvulsant therapy

  • Sexual function and fatigue

  • Venous thromboembolism (VTE)

bottom of page