The Complete Guide to Hormone Therapy

Gender-Affirming Hormone Therapy (GAHT), commonly referred to as HRT (Hormone Replacement Therapy), is the most widespread medical treatment among trans people who desire a medical transition. It consists of the administration of sex hormones to bring the body’s hormonal profile into the typical range of the affirmed gender: estrogens for trans women, testosterone for trans men.

This article is a reference guide: it covers the medications used, dosages, clinical protocols, the timeline of changes, medical monitoring, the pathway to access it in Italy, options for non-binary people, and the risks of self-medication. For in-depth information specifically on physical changes and long-term management, please refer to our dedicated articles.

The following information is based on the Endocrine Society guidelines (2017), the WPATH Standards of Care version 8 (2022), and the UCSF guidelines for transgender care (2016) [1][2][3]. They do not replace medical advice: every journey is individual and must be managed with an experienced endocrinologist.

What hormone therapy is and why it’s important

Hormone therapy does not create something artificial. It induces the same changes as a natural puberty, using the same molecules that the human body naturally produces: estradiol and testosterone. The goal is to align secondary sexual characteristics with the person’s gender identity, reducing dysphoria and improving quality of life.

The scientific data regarding its effectiveness is solid. A systematic review by Aldridge et al. (2020) confirmed that hormone therapy is associated with a significant reduction in depression and anxiety in trans people [10]. Colizzi et al. (2014) demonstrated a reduction in cortisol levels and psychobiological stress markers after 12 months of treatment [9]. These benefits are not purely subjective: they are measurable and replicable.

Hormone therapy is recommended by all major international medical organizations—Endocrine Society, WPATH, and APA—as a safe and effective treatment for people with gender incongruence who desire it. The WHO, for its part, depathologized gender incongruence with the ICD-11 (2022), though it does not publish specific clinical guidelines on hormone therapy.

Feminizing therapy (trans women)

Feminizing therapy has two goals: introducing estrogens to develop female sexual characteristics and suppressing testosterone to reduce male ones. In clinical practice, this translates into combining an estrogen with an anti-androgen.

Estrogens: types and routes of administration

The hormone used is estradiol (17-beta estradiol), the bioidentical form of estrogen produced by the ovaries [4]. Ethinylestradiol, a synthetic estrogen found in many contraceptives, is no longer recommended for trans people due to a significantly higher thromboembolic risk [1].

Available routes of administration are:

Oral estradiol (pills) The most accessible and widely used formulation. Estradiol valerate pills (Progynova, Estrofem) are taken orally or sublingually. Typical dosages range from 2 to 6 mg per day, with most patients stabilizing on 4-6 mg. The sublingual route (dissolving pills under the tongue) bypasses first-pass hepatic metabolism, potentially reducing the impact on the liver and the production of coagulation factors [4]. Endocrine Society guidelines recommend dosages that achieve serum estradiol levels between 100 and 200 pg/mL [1].

Transdermal estradiol (patches or gel) Patches (Estraderm, Dermestril) and gels (Estreva, Sandrena) release estradiol through the skin, completely bypassing first-pass hepatic metabolism. This route is associated with a significantly lower thromboembolic risk compared to the oral route. A meta-analysis by Mohammed et al. (2015) confirmed that transdermal estrogens do not increase the risk of venous thrombosis, unlike oral ones [5]. For this reason, the transdermal route is highly recommended for patients with cardiovascular risk factors (over 40 years of age, smoking, obesity, family history of thrombosis) [1]. Typical dosages are 100-200 mcg/day for patches and 1-4 mg/day for gel.

Injectable estradiol Injectable estradiol valerate or cypionate (intramuscular or subcutaneous) is less common in Italy than in other countries, but is used in some centers. Injections offer more stable blood levels if administered at regular intervals (every 5-7 days for valerate, every 7-14 days for cypionate). Typical dosages are 5-20 mg of estradiol valerate every two weeks, or 2-5 mg of estradiol cypionate every 7-14 days [1].

Anti-androgens

Administering estrogen alone is generally not enough to completely suppress testosterone production in the first months of therapy. Therefore, an anti-androgen is added, at least until testosterone levels stably drop into the female range (below 50 ng/dL) [1]. After an orchiectomy, the anti-androgen is no longer necessary.

Cyproterone acetate (CPA) The most used anti-androgen in Europe [4]. It is a progestin with potent anti-androgenic action: it suppresses the secretion of gonadotropins (LH and FSH) and partially blocks androgen receptors. Dosages used in clinical practice are 10-25 mg per day; higher dosages (50-100 mg), once common, are now discouraged due to a dose-dependent risk of meningioma and liver side effects. Wiepjes et al. (2019) analyzed long-term risks, confirming that low-dose cyproterone acetate has an acceptable safety profile, but recommending monitoring of prolactin and neurological symptoms [7]. Other side effects include fatigue, mood depression, and weight gain. Cyproterone acetate is not available in the United States, but it is the standard in Italy and the rest of Europe.

Spironolactone A potassium-sparing diuretic with anti-androgenic action. It is the most used anti-androgen in the United States, where cyproterone is unavailable. Dosages range from 100 to 200 mg per day. Spironolactone blocks androgen receptors and partially inhibits testosterone synthesis. Its main limitations are the diuretic effect (increased urinary frequency), the risk of hyperkalemia (high blood potassium, requiring regular monitoring), and lower efficacy in suppressing testosterone compared to cyproterone acetate [3].

GnRH agonists (LHRH analogs) Medications like triptorelin (Decapeptyl) and leuprorelin (Enantone) completely suppress the production of gonadotropins and, consequently, testosterone. They are considered the most effective option with the lowest side effect profile, but their high cost limits their use. In Italy, they can be prescribed within the SSN in some specialized centers. Salway et al. (2022) confirmed their efficacy and safety in the context of gender-affirming therapy [8]. These are also the medications used as puberty blockers in trans adolescents.

Bicalutamide A non-steroidal anti-androgen used in prostate oncology, adopted off-label by some clinicians for trans women. It blocks androgen receptors without suppressing testosterone levels (which may paradoxically increase). Data on its use in trans people are limited, and major guidelines do not include it among the recommended options. The risk of hepatotoxicity, although rare, requires liver function monitoring.

The debate on progesterone

The addition of progesterone to feminizing therapy is a debated topic. Some patients and clinicians report benefits regarding breast development, mood, sleep, and libido. Prior (2019), in an editorial published in the Journal of Clinical Endocrinology & Metabolism, argued that progesterone could play a role in completing breast development (particularly in the gland’s maturation toward Tanner stage V) and in bone health, analogous to its role in cisgender female puberty [11].

However, there is a lack of specific controlled clinical trials on trans women. The Endocrine Society guidelines (2017) neither explicitly recommend nor advise against progesterone, citing insufficient data [1]. The WPATH SOC-8 (2022) acknowledges that some people request it and that clinicians may consider prescribing it, evaluating on a case-by-case basis [2].

Dosages reported in the literature are 100-200 mg of micronized progesterone (Prometrium, Progeffik) per day, taken orally before sleeping (progesterone has a sedative effect that can be useful for those with sleep problems) or rectally (better bioavailability). Potential risks include drowsiness, mood changes, and a hypothetical increased risk of breast cancer with prolonged use, although the latter comes from studies on menopausal cisgender women and may not be directly applicable.

Dosages and target levels for feminizing therapy

The Endocrine Society guidelines (2017) indicate the following targets [1]:

• Serum estradiol: 100-200 pg/mL (367-734 pmol/L)
• Serum testosterone: under 50 ng/dL (1.7 nmol/L)

Typical recommended dosages:

Medication	Route	Dosage
Estradiol valerate	Oral	2-6 mg/day
Estradiol	Transdermal patch	0.025-0.2 mg/day
Estradiol valerate	Intramuscular	5-20 mg every 2 weeks
Estradiol cypionate	Intramuscular/subcutaneous	2-5 mg every 1-2 weeks
Cyproterone acetate	Oral	10-25 mg/day
Spironolactone	Oral	100-200 mg/day
Triptorelin	Intramuscular	3.75 mg every 4 weeks

Dosages are adjusted gradually based on blood tests, starting from the lower limit and increasing until target levels are met. The approach is “start low, go slow” [3].

Masculinizing therapy (trans men)

Masculinizing therapy is pharmacologically simpler: testosterone is used without the need for an additional medication to suppress endogenous estrogens. Testosterone, at adequate dosages, autonomously suppresses the hypothalamic-pituitary-ovarian axis, reducing estrogen production and stopping the menstrual cycle [14].

Testosterone: types and routes of administration

Injectable testosterone (enanthate or cypionate) The most widespread formulation globally. Testosterone enanthate (Testoviron, Testo Enant) and cypionate are testosterone esters administered intramuscularly, typically every 1-2 weeks [14]. Some protocols involve subcutaneous injection, which is less painful and equally effective. Typical dosages are 50-100 mg per week or 100-200 mg every two weeks [1]. Biweekly injections can produce fluctuations in blood levels (a peak after the injection, a trough before the next), which some people perceive as mood and energy swings.

Injectable testosterone undecanoate (Nebido) A long-acting formulation administered intramuscularly every 10-14 weeks. It provides more stable levels than testosterone enanthate, with fewer fluctuations. The standard dosage is 1000 mg (4 mL) every 10-14 weeks [1]. The cost is higher, but the injection frequency is much lower. It requires administration in a medical setting due to the injected volume and the (very rare) risk of pulmonary oil microembolism.

Transdermal testosterone gel The gel (Testogel, Tostrex, Androgel) is applied daily to the skin (shoulders, arms, or abdomen) and provides very stable hormonal levels, without the peaks and valleys of injections [14]. Typical dosages are 50-100 mg/day. It requires care to avoid transferring it to others (partners, children) through skin-to-skin contact before it has fully absorbed. The monthly cost is generally higher compared to injectable testosterone.

Transdermal testosterone patches Patches (Testopatch) release testosterone continuously through the skin. They are less commonly used than gel due to potential skin irritation at the application site. Dosages are 2.5-7.5 mg/day.

Dosages and target levels for masculinizing therapy

The Endocrine Society guidelines (2017) indicate [1]:

• Serum testosterone: 300-1000 ng/dL (10.4-34.7 nmol/L), in the physiological male range
• Serum estradiol: under 50 pg/mL (typically, it is not a primary target)

Recommended dosages:

Medication	Route	Dosage
Testosterone enanthate/cypionate	Intramuscular/subcutaneous	50-100 mg/week or 100-200 mg every 2 weeks
Testosterone undecanoate	Intramuscular	1000 mg every 10-14 weeks
Testosterone gel 1%	Transdermal	50-100 mg/day
Testosterone patch	Transdermal	2.5-7.5 mg/day

As with feminizing therapy, the starting dose is low and adjusted based on blood levels. The timing of blood draws is crucial: for biweekly injectable formulations, blood should be drawn mid-cycle (halfway between two injections) or at trough (just before the next injection), depending on the center’s protocol [3].

Timeline of changes: what to expect month by month

Every body responds uniquely to hormone therapy. The following timelines are based on the Endocrine Society guidelines (2017) and UCSF guidelines (2016) and represent statistical averages, not individual guarantees [1][3].

Feminizing therapy: timeline

Change	Onset	Maximum effect
Decreased libido	1-3 months	1-2 years
Decreased spontaneous erections	1-3 months	3-6 months
Softer, less oily skin	1-3 months	Unknown
Breast growth	3-6 months	2-5 years
Fat redistribution (hips, thighs)	3-6 months	2-5 years
Decreased muscle mass	3-6 months	1-2 years
Decreased body hair	6-12 months	3+ years
Slowing of baldness	1-3 months	1-2 years
Testicular atrophy	3-6 months	2-3 years
Possible infertility	Variable	Variable

Voice does not change with estrogens: the vocal drop that occurs during a testosterone-driven puberty is irreversible. To change the voice, speech therapy or, in some cases, gender-affirming surgery is necessary.

Masculinizing therapy: timeline

Change	Onset	Maximum effect
Oilier skin, acne	1-6 months	1-2 years
Increased libido	1-3 months	Unknown
Clitoral growth	1-3 months	1-2 years
Cessation of menstrual cycle	1-6 months	-
Hair growth (face and body)	6-12 months	4-5 years
Deepening of voice	3-12 months	1-2 years
Fat redistribution (abdomen)	3-6 months	2-5 years
Increased muscle mass	6-12 months	2-5 years
Androgenetic alopecia (if predisposed)	6-12 months	Variable
Possible infertility	Variable	Variable

For an in-depth analysis of individual changes, along with clinical study data, refer to the article on physical changes of hormone therapy.

Blood tests and monitoring

Regular monitoring is the foundation of hormone therapy safety. It’s not a formality: blood tests guide dosage adjustments and allow for the early detection of potential problems.

Which tests and when

The Endocrine Society guidelines (2017) and UCSF guidelines (2016) recommend the following schedule [1][3]:

First year: every 3 months

• Serum estradiol and testosterone
• Complete Blood Count (CBC, with special attention to hematocrit for trans men)
• Liver function (AST, ALT, GGT)
• Lipid profile (total cholesterol, HDL, LDL, triglycerides)
• Fasting glucose
• Electrolytes (potassium, sodium) — mandatory if taking spironolactone
• Prolactin (for trans women, especially those on cyproterone acetate)

Subsequent years: every 6-12 months

• Same tests, with reduced frequency once stable levels are reached
• Bone densitometry (DEXA) every 1-2 years if there are risk factors for osteoporosis

Target levels and how to interpret them

Hormone levels must be interpreted within the overall clinical context, not as isolated numbers. An estradiol level at the lower end of the target range may be sufficient if changes are progressing satisfactorily and the person feels well. A level at the high end might not be enough if testosterone is not adequately suppressed.

For trans women, the goal is to bring estradiol between 100 and 200 pg/mL and testosterone under 50 ng/dL [1]. If testosterone remains elevated despite therapy, the anti-androgen may need adjusting or estradiol increased (which at sufficient levels autonomously suppresses testosterone production via feedback on the hypothalamic axis).

For trans men, the goal is to bring testosterone between 300 and 1000 ng/dL [1]. Pay attention to hematocrit: testosterone stimulates red blood cell production. A hematocrit above 54% requires a dose reduction or a longer interval between injections, as excessively high values increase blood viscosity and cardiovascular risk [3].

Starting hormone therapy in Italy

The pathway to accessing hormone therapy in Italy is structured but varies significantly from region to region. Understanding the steps helps to navigate it and reduce waiting times. For a detailed guide on the entire transition pathway, see the article on starting transition in Italy.

The standard pathway

The most common pathway involves:

1. First contact with a specialized center. Referral centers in Italy include SAIFIP (Rome), CIDIGEM (Turin), Careggi hospital (Florence), Bari Polyclinic, Federico II (Naples), and other regional centers. An updated list is available on Infotrans.it and the ONIG website [13]. Initial contact can be made directly, through a general practitioner, or via local associations.

2. Psychological evaluation. Italian protocols, in line with the ONIG framework, generally require a period of psychological support—typically 6-12 months—during which gender incongruence is explored, expectations are assessed, and the person is prepared for subsequent steps. This phase is not a “test” to prove being “trans enough”: it is a support pathway. However, its length and format vary greatly between centers, and some people experience it as a bureaucratic hurdle.

3. Endocrinological care. At the end of the evaluation, the center’s endocrinologist sets up the hormone therapy, prescribing baseline tests and defining the pharmacological protocol.

4. Regular follow-up. Check-ups every 3-6 months in the first year, adjusting dosages based on test results and clinical response [1].

Informed consent vs. gatekeeping

The debate between the “informed consent” model and the “gatekeeping” model is very much alive in Italy. In the traditional model (gatekeeping), the clinician decides whether the person “deserves” access to therapy based on diagnostic criteria and a standardized assessment pathway. In the informed consent model, the adult is considered capable of deciding for themselves after receiving comprehensive information on risks, benefits, alternatives, and limitations of the treatment.

WPATH SOC-8 (2022) shifted the approach toward informed consent, reducing the role of psychiatric diagnosis as a mandatory prerequisite [2]. In Italy, practices vary: some centers maintain a traditional approach with long pathways and strict requirements, while others adopt models closer to informed consent. The trend is toward gradual simplification, but regional differences remain stark.

Some private endocrinologists prescribe hormone therapy under an informed consent model after an appropriate medical evaluation, without requiring a formal psychological pathway. This is a legitimate option, but the costs are borne out-of-pocket by the individual.

Realistic timelines

The time it takes to start hormone therapy in Italy varies enormously:

• Public center with long waitlists: from 6 months to over 2 years from the first request to the first prescription
• Public center with reasonable wait times: 4-8 months
• Private informed consent pathway: 1-3 months
• Private endocrinologist (with existing documentation): a few weeks

These timelines can be frustrating. Local associations (such as MIT, Libellula, Arcigay, and many others) offer guidance and support to help navigate the system.

Costs in Italy

Since 2020, thanks to AIFA determinations 104272 and 104273, hormonal medications for gender affirmation are provided free of charge by the SSN across Italy [12]. This is a major change: previously, coverage depended on the region.

Costs with the SSN

• Estradiol (pills or patches): standard co-pay (ticket) or exemption, just a few euros per box
• Injectable testosterone enanthate: among the cheapest options, covered by the SSN
• Testosterone gel: covered by the SSN with an appropriate prescription
• Cyproterone acetate: covered by the SSN
• Spironolactone: covered by the SSN
• GnRH agonists (triptorelin, leuprorelin): covered in some centers, very expensive if bought privately (200-400 euros/month)
• Blood tests: SSN co-pay (a few euros per panel) or free with exemption

Private costs

Those who choose an entirely private route can expect:

• Endocrinological visit: 100-250 euros
• Monthly hormone therapy: 30-80 euros depending on the drug
• Blood tests (full panel): 50-150 euros
• Psychological sessions (if required): 50-100 euros per session

Regional disparities in SSN access remain significant. In some regions, the process is smooth and well-organized; in others, people face long waits, poorly trained professionals, or bureaucratic hurdles [13].

Common concerns and myths

“Hormone therapy is dangerous”

Like any medical treatment, hormone therapy carries risks. But these risks are known, manageable with monitoring, and proportional to the benefits. The thromboembolic risk with oral estrogens is real but minimized with transdermal routes [5]. Cyproterone acetate at high doses is associated with an increased risk of meningioma, but at low doses (10-25 mg) the risk is very low [7]. Testosterone can raise hematocrit, but regular monitoring prevents complications. Long-term safety is supported by decades of clinical data.

“Hormones change your personality”

No. Hormone therapy influences mood (increased emotional reactivity with estrogens, possible initial irritability with testosterone), but it does not alter a person’s personality, values, memories, or identity [9]. Emotional changes are physiological and comparable to those of a natural puberty.

“The results are the same for everyone”

No. Individual variability is enormous. Genetics, age, BMI, receptor response, and many other factors influence the outcome. Comparing one’s changes to those of others is rarely helpful and can lead to unjustified frustration.

“You have to choose: all effects or none”

Not necessarily. Low-dose and limited-duration protocols exist for those who desire partial masculinization or feminization [2]. The effect is not an indivisible package: some changes are more dose-dependent than others, and an experienced clinician can help modulate the treatment.

Drug interactions

Hormone therapy can interact with other medications. It is essential that the prescribing doctor is informed of all ongoing treatments.

The most relevant interactions include [3]:

• Antiepileptic drugs (carbamazepine, phenytoin, topiramate): they induce liver enzymes and can reduce estradiol and testosterone levels, requiring dosage adjustments.
• Antibiotics (rifampin): a potent enzyme inducer; significantly reduces hormone levels.
• Antiretrovirals for HIV: some classes can interact with sex hormone metabolism. Monitoring of levels should be intensified.
• Warfarin and anticoagulants: estrogens affect coagulation and can alter the effectiveness of anticoagulants. INR monitoring should be intensified.
• Diabetes medications: hormone therapy can alter insulin sensitivity. The dosage of antidiabetic drugs may require adjustment.
• SSRIs and other antidepressants: there are no significant direct pharmacological interactions, but mood effects overlap. It is helpful to distinguish the effects of hormones from those of psychiatric drugs.
• Spironolactone and ACE-inhibitors/ARBs: a combination that increases the risk of hyperkalemia. Potassium must be monitored closely.

Generally, hormone therapy is compatible with the vast majority of commonly used drugs. The UCSF guidelines (2016) offer a detailed breakdown of drug interactions within the context of GAHT [3].

HRT for non-binary people

The WPATH SOC-8 guidelines (2022) explicitly acknowledge that not all transgender people desire a full transition to the opposite pole of the gender spectrum [2]. Some non-binary people desire partial masculinization or feminization, while others desire specific effects (e.g., voice deepening without full body masculinization, or breast development without full testosterone suppression).

Available protocols include:

• Low-dose testosterone: lower dosages than standard (e.g., 25-50 mg/week of testosterone enanthate, or a half dose of gel) may produce some changes more slowly and potentially to a lesser extent. However, it is important to know that irreversible changes (voice, beard) can still occur on a low dose, just more slowly. There is no dose that guarantees “only some effects”: testosterone acts on all tissues with androgen receptors.

• Low-dose estrogens: a similar approach for AMAB non-binary people. Lower dosages may produce more gradual and less pronounced feminization, but again, it’s impossible to select a priori which changes will occur.

• Selective modulation with anti-androgens: some AMAB non-binary people take only an anti-androgen without estrogens to reduce the effects of testosterone (body hair, baldness, sebum) without inducing feminization. This option is less studied and must be managed carefully to avoid complete hormone deficiency.

• Limited-duration therapy: some choose to take hormones for a defined period, achieve desired irreversible changes (such as voice deepening from testosterone), and then stop, keeping those changes while reversible ones regress.

These approaches require an experienced endocrinologist open to dialogue. Not all clinicians are familiar with protocols for non-binary people, and finding the right professional may require some research. Local LGBTQ+ associations can often recommend doctors with experience in this area.

Self-medication: risks and harm reduction

It is a fact: a portion of trans people access hormone therapy without a medical prescription, buying drugs online, through informal networks, or in countries where they are available over the counter. A study by Metastasio et al. (2018) documented that self-medication is a significant phenomenon, driven by long waiting lists, perceived excessive gatekeeping, the costs of private healthcare, or the lack of accessible centers in one’s area [15].

This article does not encourage self-medication (DIY HRT), but acknowledges that ignoring the phenomenon won’t make it disappear. A harm reduction approach is far more useful than moral judgment.

Real risks of self-medication

• Inappropriate dosages: without blood tests, it’s impossible to know if hormone levels are in the correct range. Doses that are too high increase risks (thrombosis, polycythemia, hepatotoxicity) without improving results. Doses that are too low are ineffective.
• Counterfeit or low-quality drugs: medications bought online without guarantees may contain active ingredients different from what is stated, contaminants, or inaccurate dosages.
• Lack of monitoring: the most serious risks of hormone therapy (thrombosis, polycythemia, meningioma with high-dose CPA, hyperkalemia with spironolactone) are manageable with monitoring but potentially dangerous without it.
• Undetected interactions: without a doctor who knows your full clinical picture, interactions with other medications can go unnoticed.
• Isolation: self-medication often happens in solitude, without the psychological support that the transition process may require.

Harm reduction principles

For those who find themselves self-medicating, the following guidelines can reduce risks:

• Get regular blood tests anyway: you can request a hormonal and blood chemistry panel even without a specific HRT prescription. Knowing your levels is essential.
• Use bioidentical estradiol, never ethinylestradiol: ethinylestradiol (found in birth control pills) has a much higher thromboembolic risk and is contraindicated [1].
• Prefer known pharmaceutical formulations: medications from recognized brands (Progynova, Testoviron, Androcur) bought from verifiable sources are preferable to products without guarantees.
• Start with low doses: the “start low, go slow” principle is even more vital without medical supervision [3].
• Do not mix anti-androgens without monitoring: spironolactone requires potassium checks; cyproterone requires monitoring of liver function and prolactin [7].
• Still look for a doctor: even if you are already self-medicating, you can approach a doctor (GP or endocrinologist) and speak openly about your situation. Many professionals would prefer taking over your care rather than leaving you unsupervised.

The goal is not to normalize self-medication, but to recognize that barriers to accessing proper hormone therapy are a primary cause of the phenomenon [15]. Reducing these barriers is the most effective strategy to reduce self-medication.

Risks and monitoring: what the science says

Hormone therapy, like any long-term pharmacological treatment, carries specific risks that must be understood, monitored, and managed. Minimizing them would be dishonest; exaggerating them would be equally incorrect. This section addresses them one by one using scientific literature.

Cardiovascular risks

The primary risk associated with estrogen therapy is venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism. This risk is dose-dependent and strongly influenced by the route of administration: oral estrogens increase the hepatic production of clotting factors, while the transdermal route (patches, gels) bypasses the liver and does not significantly increase thromboembolic risk [5]. For people with risk factors (over 40, smoking, obesity, personal or family history of thrombosis), the transdermal route is strongly recommended [1].

For testosterone therapy, the cardiovascular profile is different: testosterone can alter the lipid profile (lowering HDL, raising LDL) and increase blood viscosity due to polycythemia. Regular monitoring of the lipid profile and hematocrit is essential [3].

Hematological risks

Testosterone stimulates erythropoiesis (red blood cell production). A hematocrit above 54% is considered an alarm threshold: at that level, blood becomes more viscous, increasing the risk of thrombotic events [1]. Management involves a dose reduction or lengthening the interval between administrations. In rare cases, therapeutic phlebotomy may be necessary. Polycythemia is the most common hematological risk of testosterone therapy and is entirely manageable through monitoring.

Impact on fertility

Hormone therapy can compromise fertility, but not universally or always irreversibly. Estrogen therapy reduces sperm production (from oligospermia to azoospermia), an effect that may be partially reversible after suspending treatment, although there are no guarantees. Testosterone can suppress ovulation, but the literature reports cases of pregnancies occurring during or after testosterone therapy [17]. Anyone who wants to maintain the possibility of having biological children should discuss fertility preservation before starting therapy. A detailed discussion can be found in the dedicated section below and in the article on trans fertility.

Liver

Both estrogens and testosterone can affect liver function. Cyproterone acetate, particularly at high doses, has been associated with hepatotoxicity [7]. For this reason, liver function tests (AST, ALT, GGT) are part of the standard monitoring panel, with checks every 3 months in the first year and every 6-12 months thereafter [1][3]. In the vast majority of cases, liver alterations are mild and reversible by adjusting the therapy.

Bone density

Sex hormones are critical for maintaining bone density. Proper hormone therapy, which keeps hormone levels in the physiological range, protects the bones. The risk of osteoporosis emerges when hormone levels are insufficient—for example, in cases of doses that are too low, poor adherence to therapy, or after a gonadectomy without adequate hormone replacement [1]. A bone density scan (DEXA) is recommended for people with additional risk factors.

Effects on mental health

The scientific literature consistently documents a positive effect of hormone therapy on the mental health of trans people. A study by Tordoff et al. (2022) demonstrated that transgender and non-binary people who receive gender-affirming care show a significant reduction in depression (a 60% reduction) and suicidality in the 12 months following the start of treatment [16]. This data adds to Colizzi et al. (2014), who documented a reduction in biological stress markers [9], and the systematic review by Aldridge et al. (2020) [10].

This doesn’t mean hormone therapy is a cure-all for every mental health issue. Trans people may have pre-existing or co-occurring psychological conditions that require independent treatment. But the data is clear: for people with gender incongruence, hormone therapy reduces psychological distress in a measurable and replicable way.

Medical supervision vs. self-medication

The factor that most influences the safety of hormone therapy isn’t the medication itself, but the quality of the monitoring. With regular testing and endocrinological supervision, the risks described above are manageable and severe complications are rare. Without monitoring—as in the case of self-medication—these same risks become significantly more dangerous [15]. An undetected elevated hematocrit, unmonitored hyperkalemia from spironolactone, or too high a cyproterone dose can have serious consequences. Medical supervision is not a luxury: it is an integral part of the treatment’s safety.

Fertility and preservation

The impact of hormone therapy on fertility is a major concern for many trans people and their families. Addressing this topic clearly and comprehensively is critical, especially because decisions regarding preservation should ideally be made before starting therapy.

Estrogen therapy and fertility

Estrogens suppress the hypothalamic-pituitary-testicular axis, progressively reducing sperm production. As therapy continues, severe oligospermia or azoospermia (total absence of sperm in the ejaculate) can occur. This effect may be partially reversible after suspending the therapy: some studies report a recovery of spermatogenesis after months of interruption, but full recovery is not guaranteed, especially after prolonged therapy [17]. Orchiectomy makes sterility permanent.

Sperm cryopreservation is the most accessible and established preservation option. Ideally, it should be done before starting hormone therapy, when sperm quality is optimal. However, even during therapy—provided a temporary suspension and semen evaluation occur—it may be possible to collect and store viable samples.

Testosterone therapy and fertility

Testosterone suppresses ovulation through negative feedback on the hypothalamic-pituitary-ovarian axis. However, this suppression is neither always complete nor permanent: literature reports pregnancies occurring both during and after the suspension of testosterone therapy [17]. Testosterone is not a reliable contraceptive.

Oocyte cryopreservation (egg freezing) is the main preservation option for trans men. It requires an ovarian stimulation cycle with daily injections of gonadotropins for about 10-14 days, followed by egg retrieval under sedation. This process can be emotionally difficult for those who experience dysphoria related to reproductive organs. It should be discussed openly with the medical team.

Practical information for Italy

In Italy, fertility preservation is available at Medically Assisted Procreation (PMA) centers across the country. Some practical points:

• Sperm cryopreservation: simple procedure (sample collection via masturbation), relatively low cost (100-300 euros for collection, plus an annual storage fee of about 150-300 euros).
• Oocyte cryopreservation: more complex and expensive procedure (hormonal stimulation + egg retrieval), with costs ranging from 1,500 to 4,000 euros, plus an annual storage fee.
• SSN Access: coverage by the SSN for fertility preservation in trans people varies by region. Some regions include it, others do not. It is advisable to inquire at your referral center.
• Timing: preservation should ideally be done before starting hormone therapy. If therapy is already underway, a temporary suspension (at least 3-6 months) may allow for sufficient gonadal function recovery to proceed with collection.

The decision on fertility preservation is personal: not all trans people wish to have biological children, and not everyone has the financial or emotional resources to undergo the procedure. The important thing is that the choice is informed and that the opportunity to discuss it is offered before starting therapy [2][17].

Conclusion

Hormone therapy is an established medical treatment, backed by decades of research and recommended by all major international medical organizations [1][2]. It is not a decision to be taken lightly, but it’s also not a leap into the dark: the medications are known, the effects are predictable, and the risks are manageable with monitoring.

What makes the journey complex, in Italy as elsewhere, is not the medicine itself but access: waiting times, variability between centers, gatekeeping, and private healthcare costs. Knowing your pharmacological options, protocols, rights, and available resources is the first step to navigating this path with awareness.

Every trans person deserves to make informed decisions about their own body, supported by competent and respectful professionals. This guide aims to be a tool in that direction—a starting point, not a finish line. For those considering starting, for those who have just started, and for those who simply want to better understand what they are taking and why.

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