Last updated July 30, 2025

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This report was produced by Gemini Deep Research. It is for educational purposes only and should not be considered medical advice.

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Introduction

Hormone replacement therapy (HRT) refers to medical treatments that supplement or replace naturally occurring hormones in the body. These therapies address hormonal deficiencies and help align physical characteristics with gender identity. Hormone administration can cause significant physiological changes, making individualized treatment plans essential under the guidance of experienced healthcare professionals. This comprehensive guide serves as an in-depth resource on adult HRT, focusing specifically on transgender individuals assigned male at birth (AMAB)—both nonbinary and binary transgender men—as well as intersex individuals with diverse hormonal needs.

Testosterone Hormone Replacement Therapy

Testosterone, a primary androgen, plays a crucial role in the development and maintenance of masculine characteristics. For individuals seeking masculinization, various formulations and delivery methods of testosterone are available through hormone replacement therapy.

Detailed Overview of Testosterone Formulations and Delivery Methods

Injectable Testosterone

Several esterified forms of testosterone are available for injection, each with a different pharmacokinetic profile influencing the frequency of administration.

• Testosterone Enanthate: This formulation is typically administered via deep intramuscular injection into the buttock muscle every 2 to 4 weeks by a healthcare professional, though self-administration may be possible in some cases. The injection should be performed slowly and deeply, avoiding veins. Healthcare providers should observe patients for at least 30 minutes following injection to monitor for adverse reactions.Dosage varies significantly (50-400 mg) and is carefully adjusted based on factors such as age, individual response, and side effects. For binary transgender men (FTM), starting doses typically range between 50-80 mg every two weeks or 25-40 mg weekly, with maintenance dosages often between 100-200 mg every two weeks or 50-100 mg weekly. Nonbinary individuals may prefer lower doses (around 25 mg weekly) for more gradual masculinizing effects.Dosage adjustments should be guided by symptomatic response and regular monitoring of testosterone levels, targeting the mid-normal male physiological range (approximately 500-700 ng/dL when measured by mass spectrometry). Intramuscular injection provides very high bioavailability (approaching 95%). Following injection, serum testosterone levels typically peak within 36-48 hours and gradually decline, becoming subtherapeutic after approximately 3-4 weeks.Testosterone enanthate helps treat low testosterone levels and delayed puberty, improving muscle mass, strength, energy levels, libido, voice deepening, and facial/body hair growth. It can enhance psychological well-being, reduce gender dysphoria, and reverse hypogonadism effects.Potential risks include acne, injection site pain/swelling, blood clots, stroke, heart attack, liver problems, high blood pressure, sleep apnea, high calcium levels, mood changes, anxiety, depression, decreased sperm count, and breast enlargement/tenderness. Misuse can lead to addiction, heart failure, and hallucinations. Severe allergic reactions are possible, particularly with sesame oil-containing formulations. Testosterone enanthate can interact with diabetes medications, blood thinners, and corticosteroids. Long-term use may cause liver problems, necessitating regular liver enzyme monitoring. Other risks include fluid retention, swelling, and increased prostate cancer risk, especially in older males.
• Testosterone Cypionate: Similar to testosterone enanthate, testosterone cypionate is administered via intramuscular injection, typically every 1 to 4 weeks. Self-administration is often possible with proper training. Dosage generally ranges between 50-400 mg, with healthcare providers making adjustments based on individual needs. For transgender men, starting doses are similar to those of enanthate. Treatment aims for testosterone levels of 450-600 ng/dL. Intramuscular injection provides very high bioavailability, with levels peaking for 4-5 days after injection before gradually declining to subtherapeutic levels by day 14. Subcutaneous delivery is also effective, often with a 10-15% lower initial dose when transitioning from intramuscular administration. Benefits include treating low testosterone, inducing male puberty, facilitating masculinization for transgender individuals, providing more consistent hormone levels, and alleviating symptoms like fatigue, low libido, reduced muscle mass, cognitive difficulties, and mood fluctuations. Potential risks include acne, injection site reactions, cardiovascular issues, blood clots, liver problems, mood changes, sleep apnea, prostate concerns, and fertility issues. It may interact with diabetes medications and blood thinners, and long-term high-dose use might increase risks of liver problems, blood clots, fluid retention, and prostate cancer, particularly in older individuals.
• Testosterone Propionate: This formulation requires more frequent administration due to its shorter half-life, typically via intramuscular injection every 2 to 3 days. Dosage is tailored to the individual's condition and testosterone levels. Implantable pellets offer an alternative delivery method—six 75 mg pellets provide the equivalent of weekly 75 mg injections and last approximately three months. Intramuscular injection results in very high bioavailability with a relatively short elimination half-life of approximately 20 hours. Benefits include treating low testosterone, improving energy, mood, and libido, and increasing muscle mass, strength, and bone density. It's primarily used for androgen replacement therapy and conditions such as hypogonadism, breast cancer, low sexual desire, and delayed puberty. As a natural and bioidentical form of testosterone, it rapidly converts to the active hormone. A notable risk is injection site pain due to its short ester chain. Other side effects include masculinization symptoms (acne, increased hair growth, voice changes, increased sexual desire), potential aggressive behavior, cardiovascular concerns, liver problems, fertility issues, and injection site reactions.
• Testosterone Undecanoate: This longer-acting injectable testosterone is typically administered intramuscularly every 10-12 weeks following an initial loading phase. It's also available as oral capsules taken with food twice daily. Injectable dosing often begins with 750 mg, followed by another 750 mg after 4 weeks, then 750 mg every 10 weeks. For transgender men, typical oral dosage is 160-240 mg daily. Oral bioavailability is relatively low (3-7%) and food-dependent, while intramuscular injection provides sustained testosterone release, with levels peaking around day 7 and declining to subtherapeutic levels by week 10 after initial doses. The injectable form offers the least frequent dosing among intramuscular options, while the oral form provides a convenient injection alternative. Both effectively replace testosterone. A significant risk with injectable undecanoate is pulmonary oil microembolism and anaphylaxis, requiring at least 30 minutes of monitoring after each injection. Oral formulations may increase blood pressure and carry boxed warnings for cardiovascular events. Additional risks include decreased T4 levels and reduced sperm concentration. However, newer oral formulations haven't shown significant liver toxicity in clinical trials.

Topical Gels and Solutions

Testosterone can also be administered through topical gels and solutions, offering a needle-free alternative.

• Administration: These formulations are typically applied once daily to clean, dry, and intact skin on areas such as the shoulders, upper arms, abdomen, thighs, or underarms, and should be allowed to dry completely before dressing. It is important to wash hands thoroughly after application and to avoid skin contact with others until the gel or solution has dried to prevent unintended testosterone exposure.
• Dosage: The dosage varies depending on the specific product, such as AndroGel, Testim, Fortesta, Vogelxo, and Axiron, as well as the concentration, which is typically 1% or 1.62%. Starting doses generally range from 25 mg to 50 mg of testosterone per day and are adjusted by a healthcare professional based on individual needs. Lower doses, in the range of 12.5 to 25 mg per day for 1% gel and around 20.25 mg per day for 1.62% gel, are often used for microdosing in nonbinary individuals seeking more subtle changes.
• Absorption Rates: The bioavailability of topical testosterone gels and solutions typically ranges from approximately 8% to 14%, and can be influenced by the specific application site. Absorption may be lower when applied to the abdomen compared to other areas like the upper arms or shoulders. For AndroGel, serum testosterone levels typically peak between 16 and 22 hours after application.