Hormone Therapy: Duration and Management

One of the most frequently asked questions among trans people who are starting or considering hormone therapy is: “will I have to take hormones for the rest of my life?” The short answer is: in most cases, yes. But this answer deserves a much broader context, because the management of hormone therapy over time is a topic rich with nuances, and understanding the details helps one live with it in peace.

This article explores the duration of hormone therapy, what happens if it is interrupted, what research says about long-term safety, how medical monitoring is managed, and how to handle special situations such as travel, surgical procedures, and aging.

Why Hormone Therapy Lasts a Lifetime

To understand why hormone therapy is generally long-term, we must start from a fundamental concept: the human body needs sex hormones to function properly. This is not just about maintaining the physical changes achieved through transition, but about ensuring the overall health of the organism.

Sex hormones — estrogens and testosterone — perform essential functions that go well beyond secondary sex characteristics. They protect bones from osteoporosis, regulate cholesterol metabolism and cardiovascular risk, support cognitive functions and mood, and maintain the health of tissues throughout the body [3].

Stopping hormone therapy without the body having an endogenous source of sex hormones would mean living in a state of chronic hormone deficiency, comparable to premature menopause or andropause, but without the possibility of spontaneous recovery.

With or Without Gonads: Two Different Scenarios

The need to continue hormone therapy for life depends crucially on the presence or absence of the original gonads (ovaries or testicles).

After Gonadectomy

Those who have had their gonads removed as part of surgical transition no longer have a significant endogenous source of sex hormones. In this case, hormone replacement therapy is medically necessary, not only to maintain the changes of transition but to prevent serious health consequences [1][2].

Without hormone therapy after gonadectomy, the body experiences:

• Loss of bone density: The risk of osteoporosis increases significantly. A study by Lips et al. (1998) demonstrated that bone mineral density in trans people treated with hormones after gonadectomy remains stable over time, while without treatment the decline would be rapid and progressive [4].
• Cardiovascular deterioration: Sex hormones play a protective role in the cardiovascular system. Chronic hormone deficiency increases the risk of cardiovascular disease [3].
• Symptoms of hormone deficiency: Hot flashes, night sweats, chronic fatigue, insomnia, dry skin and mucous membranes, decreased libido, difficulty concentrating.
• Impact on mood: Increased risk of depression and anxiety, as also documented in the literature on the mental health of trans people.

The Endocrine Society guidelines (2017) and the WPATH SOC 8 (2022) are clear: hormone therapy after gonadectomy is considered an essential medical treatment and must be continued indefinitely [1][2].

With Gonads Still Present

The situation is more complex for those who have not undergone gonadectomy. In this case, the original gonads are still capable of producing sex hormones, even though their function is suppressed by hormone therapy.

If therapy is interrupted, the gonads gradually resume their activity. This means that:

• Hormone levels progressively return to pre-therapy values
• Reversible changes from hormone therapy regress (fat redistribution, muscle mass, skin quality)
• Irreversible changes remain (voice deepening from testosterone, breast development from estrogen)
• Menstrual cycles may resume in trans men

However, even in this case, the vast majority of trans people choose to continue therapy to maintain alignment between their body and their gender identity. Voluntary discontinuation is rare and, when it occurs, is generally motivated by specific reasons (side effects, desire for fertility, particular medical circumstances) rather than a desire for detransition [6].

What Happens If Therapy Is Interrupted

Understanding the consequences of interruption is important not only for those considering stopping but also for managing situations in which therapy is temporarily suspended (before surgery, during travel, due to supply issues).

Interruption With Gonads Present

The changes do not happen immediately. In the first weeks, mood and libido changes may be noticed. Over weeks or months, the body begins to return toward the previous hormonal profile. The speed of these changes varies from person to person.

For trans women who stop estrogen, endogenous testosterone resumes its activity: a return of body hair, increased muscle mass, fat redistribution, and in some cases more frequent erections may be observed. Breast tissue developed during therapy does not significantly regress.

For trans men who stop testosterone, endogenous estrogens regain the upper hand: menstrual cycles may return, fat redistributes toward the hips, and muscle mass decreases. The voice remains deep and any beard that developed remains.

Interruption Without Gonads

Without gonads, interrupting hormone therapy leads to a state of complete hormone deficiency. Symptoms manifest within days or weeks and are significant: hot flashes, intense fatigue, sleep disturbances, irritability, cognitive difficulties, joint pain [3]. In the long term, the risk of osteoporosis becomes concrete and serious [4].

This situation is analogous to that of cisgender women after surgical menopause (bilateral ovariectomy) or cisgender men after orchiectomy: in all these cases, hormone replacement therapy is the recommended standard of care [1].

Long-Term Safety: What the Studies Say

One of the most understandable concerns is about the safety of taking hormones for decades. Research on this topic has expanded considerably in recent years, and the data are overall reassuring while highlighting the need for regular medical monitoring.

Mortality Data

The study by Asscheman et al. (2011), which followed a large cohort of trans people in the Netherlands for a median of 18.5 years, found that overall mortality in trans women was higher than that of the general population, but this excess was primarily attributable to causes not related to hormone therapy (suicide, HIV, substance use) [5]. In trans men, mortality did not differ from the general population [5].

Nota and den Heijer (2020), in their review of long-term effects, concluded that hormone therapy under medical supervision has an acceptable risk profile and that the benefits in terms of quality of life far outweigh the risks [3].

Cardiovascular Risk

Cardiovascular risk is the area that requires the most attention. A meta-analysis published in the European Heart Journal Open (2023) examined aggregated data from numerous studies and concluded that trans women on estrogen therapy have a slightly increased risk of venous thromboembolic events, particularly in the first two years of treatment [11]. This risk is influenced by the type of estrogen used: transdermal estradiol presents a lower thromboembolic risk compared to oral ethinylestradiol, which is why the latter is no longer recommended by guidelines [1].

For trans men on testosterone therapy, the cardiovascular risk profile does not appear significantly different from that of cisgender men [11]. Monitoring hematocrit is important, as testosterone stimulates erythropoiesis and elevated hematocrit increases blood viscosity.

Getahun et al. (2018) and others have emphasized that modifiable risk factors (smoking, obesity, sedentary lifestyle) have a much greater impact on cardiovascular risk than hormone therapy itself [13].

Cancer Risk

The fear that hormone therapy might increase cancer risk is understandable, but available data are reassuring.

Breast cancer in trans women: The national cohort study by de Blok et al. (2019), conducted in the Netherlands on 2,260 trans women followed for a median of 18 years, found a breast cancer incidence of 46 cases per 100,000 person-years [8]. This value is higher than that of cisgender men but remains clearly lower than that of cisgender women. The authors conclude that the absolute risk remains low [8].

Prostate cancer in trans women: Documented cases are extremely rare. Testosterone suppression protects the prostate, and the risk is much lower than in cisgender men [9].

Cancers in people on testosterone therapy: Nota et al. (2018) found no significant increase in the risk of hormone-related cancers in trans men [9]. Screening for breast cancer (in residual breast tissue) and cervical cancer (if the uterus is present) is still recommended [1].

Meningioma and cyproterone acetate: Wiepjes et al. (2019) analyzed the risk of meningioma associated with prolonged use of cyproterone acetate (an anti-androgen commonly used in Europe) [10]. At high doses and for prolonged periods, the risk is slightly increased. For this reason, guidelines recommend using the minimum effective dose and monitoring for neurological symptoms [10].

The Monitoring Program

Managing long-term hormone therapy requires an ongoing relationship with one’s physician. The Endocrine Society guidelines (2017) and the UCSF guidelines (2016) provide a clear framework for the necessary monitoring [1][12].

First Year

• Every 3 months: Blood tests for hormone levels (estradiol and testosterone), complete blood count, liver function (transaminases), lipid profile
• Clinical evaluation: Blood pressure, weight, assessment of effects and any side effects

Subsequent Years

• Every 6-12 months: Same blood tests, at reduced frequency once stable levels are reached
• Periodic screenings: Bone densitometry (DEXA) every 1-2 years for those with risk factors for osteoporosis, cancer screenings according to age and sex-specific recommendations
• Cardiovascular evaluation: Monitoring of blood pressure, lipid profile, and other risk factors

Specific Checks

For trans women:

• Prolactin (annually in the first years, then every 2-3 years)
• Thromboembolic risk monitoring (especially if other risk factors are present such as smoking, obesity, immobility)
• Mammographic screening according to guidelines for cisgender women after 5 or more years of estrogen therapy [8]

For trans men:

• Hematocrit (testosterone increases red blood cell production; values that are too high require dose adjustment)
• Cervical cancer screening (if the uterus is present)
• Breast cancer screening (if mastectomy has not been performed)

Aging and Hormone Therapy

With increasing life expectancy and a growing number of trans people reaching advanced age, the management of hormone therapy during aging is becoming an increasingly relevant topic.

Menopause and Andropause

Cisgender people naturally go through menopause (decline in estrogen) or andropause (gradual decline in testosterone). For trans people on hormone therapy, this physiological transition does not occur spontaneously because hormones are administered externally.

The question that arises is: should dosages be reduced with age? Guidelines do not provide a univocal answer [12]. In general, physicians tend to adjust dosages to maintain age-appropriate hormone levels, gradually reducing them if necessary. For trans women at an advanced age, this may mean considering a switch to lower estradiol doses, similar to those used in hormone replacement therapy for cisgender women in menopause. For trans men, testosterone dosages may be reduced to approximate the levels typical of elderly cisgender men.

Bone Health in Aging

Bone density is an important concern with age. Lips et al. (1998) and subsequent studies have shown that adequate hormone therapy maintains bone density over time [4], but monitoring becomes even more important after age 50. Supplementation with calcium and vitamin D may be recommended, along with weight-bearing physical activity (walking, weight exercises).

Drug Interactions

With age, the likelihood of taking other medications for chronic conditions (hypertension, diabetes, hypercholesterolemia) increases. It is important that the physician prescribing hormone therapy is informed of all other ongoing treatments, as there can be interactions [3]. In general, hormone therapy is compatible with most common medications, but some adjustments may be necessary.

Managing Therapy in Special Situations

Before Surgery

Some surgeons require suspension of estrogen therapy 2-4 weeks before major surgery to reduce thromboembolic risk [7]. This recommendation is debated: the WPATH SOC 8 (2022) notes that thromboembolic risk can also be managed with preventive measures (compression stockings, low-molecular-weight heparin) without necessarily suspending estrogen [2]. The decision should be made on a case-by-case basis with the surgeon and endocrinologist.

For testosterone, preoperative suspension is not generally necessary, but it is important to inform the anesthesiologist because blood values (particularly hematocrit) may differ from standard reference ranges.

Travel

Traveling with hormone therapy requires a minimum of planning:

• Bring sufficient supplies: Calculate the amount needed for the entire duration of the trip, plus a safety margin
• Medical documentation: Carry a prescription or medical certificate, especially when traveling abroad. For injectable medications (syringes and vials), documentation is particularly important at airport security
• Storage: Testosterone in vials does not require refrigeration, nor does estradiol in tablets. Transdermal patches should be protected from excessive heat
• Time zones: For medications taken at fixed times, gradually adjust the dosing time to the new time zone

During Illness

In most cases, hormone therapy can be continued during common illnesses (flu, infections, etc.). Suspension should be considered in cases of illnesses that increase thrombotic risk (extended periods of bed immobility, emergency surgery, illnesses causing severe dehydration) or in cases of acute liver diseases that compromise drug metabolism [3].

It is always advisable to inform the treating physician about ongoing hormone therapy when receiving treatment for any other condition.

Costs in the United States

In the United States, the cost of hormone therapy varies significantly depending on insurance coverage and the specific medications used.

With Insurance

Most major insurance plans, including those under the Affordable Care Act (ACA), cover gender-affirming hormone therapy. Out-of-pocket costs typically include copays for office visits and prescriptions, which can range from $10 to $50 per month depending on the plan.

Without Insurance

For those without insurance, costs vary by medication:

• Estradiol (tablets or patches): $15-$60 per month depending on the formulation
• Testosterone (injectable or gel): Injectable testosterone cypionate is among the most affordable options at $20-$80 per month. Gel formulations cost more, typically $200-$400 per month without insurance
• Anti-androgens (spironolactone): $10-$30 per month
• Blood tests: A comprehensive panel can cost $100-$300 without insurance

Patient assistance programs from pharmaceutical manufacturers and community health centers (such as Planned Parenthood, Fenway Health, and Callen-Lorde) can significantly reduce costs. GoodRx and similar discount programs can also lower prescription prices.

Common Questions and Concerns

“I don’t want to depend on a medication for my whole life”

This concern is understandable and legitimate. It may help to consider that millions of cisgender people take long-term therapies for chronic conditions, from hormone replacement therapy during menopause to insulin for diabetes, from levothyroxine for hypothyroidism to medications for hypertension. Hormone therapy for trans people follows the same logic: it is a treatment that improves quality of life and protects health, not a dependency.

“What if the medications become unavailable?”

The molecules used in hormone therapy (estradiol, testosterone) are essential medications produced by numerous companies worldwide. Temporary shortages are possible for specific formulations (a particular gel, a certain type of patch), but equivalent alternatives are always available. The situation is different from that of highly specialized medications with a single manufacturer.

“Do risks increase over the years?”

The available data, which now cover follow-ups of 20-30 years in some cohorts, do not show an exponential accumulation of risks over time [5]. The risks of hormone therapy are greatest in the first years (especially thromboembolic risk with estrogen) and tend to stabilize [7]. The most important factor for long-term safety remains regular medical monitoring and management of modifiable risk factors [3].

“Can I reduce the dose over time?”

In many cases, yes. Once the desired changes have been achieved and stabilized, it is possible to evaluate with one’s physician a dosage reduction, maintaining hormone levels sufficient for health but not necessarily at the upper limits of the range [12]. This approach may be particularly appropriate with advancing age.

Conclusion

Hormone therapy is, in practice, a long-term commitment. For those who have undergone gonadectomy, it is a medical necessity; for those who still have their gonads, it is a choice that the vast majority of trans people make consciously to maintain alignment between their body and their identity.

The scientific data accumulated over decades of clinical practice — from the Dutch cohort studies to international guidelines — confirm that long-term hormone therapy, under adequate medical monitoring, has an acceptable safety profile and documented benefits for quality of life and overall health [3][5].

The key is continuity in the relationship with one’s physician, regular monitoring, and the awareness that taking care of one’s body is an act of responsibility toward oneself, not a burden. As with any aspect of medical transition, accurate information is the best antidote to fear.