Dr. Fatimah Hamade, PharmD
Understanding Male Hypogonadism, Hormone Balancing, and the Role of Personalized Compounding in Optimizing Testosterone Therapy
Abstract
This article reviews the clinical foundations of male hypogonadism, testosterone evaluation, and treatment options, with an emphasis on how compounding pharmacists tailor hormone therapies for safety, efficacy, and individualized patient needs. It also explores compounded ED treatments, absorption strategies, monitoring considerations, and collaborative approaches to men’s health.
Introduction to Male Hypogonadism
Male hypogonadism occurs when the testicles do not produce sufficient testosterone, resulting in low serum testosterone levels. This condition may arise from impaired testicular production, disrupted hypothalamic-pituitary signaling, elevated estrogen, or age-related decline.1 Testosterone replacement is the treatment of choice for testosterone deficiency, defined as low serum testosterone combined with clinical symptoms. In men, low testosterone is identified through two separate morning measurements of total serum testosterone levels below 300 ng/dL, drawn after an overnight fast.2 Morning measurements are essential because testosterone peaks between 3 AM and 8 AM. Levels decline quickly within 30 minutes of waking. For topical formulations, it is ideal to measure serum levels 2 to 4 hours post-application.
Role of Estrogen in Men
Estrogen plays a critical role in men’s health, supporting libido, bone density, cognition, and metabolism. An imbalance in the testosterone-to-estradiol (T:E2) ratio can exacerbate symptoms such as low libido or erectile dysfunction (ED), fatigue, hair thinning, depressed mood, and reduced vitality.3
Laboratory Evaluation and Monitoring
Comprehensive initial laboratory evaluation should include total and free testosterone, estradiol (E2), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), prostate-specific antigen (PSA), comprehensive metabolic panel (CMP), and hemoglobin/hematocrit levels. The target range for total testosterone typically falls between 450 and 600 ng/dL, with dose adjustments guided by both laboratory results and clinical response. Monitoring after therapy initiation depends on the formulation used, with routine follow-up recommended every six to twelve months. Hematocrit levels should be monitored every three to six months, as values above 52% may increase the risk of clotting.4
Testosterone Replacement Options
Testosterone replacement is available in multiple forms, including topical gels and solutions, transdermal patches, intranasal gels, injectables, implantable pellets, oral capsules, buccal products, and sublingual troches.5 The choice of formulation may depend on accessibility, ease of use, cost, and insurance coverage. While multiple branded and generic topical products are available, compounded options allow for personalized dosing and formulation. All topical products carry a risk of accidental exposure, potentially causing virilization in women and children.6 Risk mitigation strategies include covering application sites with clothing, washing hands thoroughly after application, and avoiding contact or washing off the product via bathing or swimming during the recommended absorption interval. Topical formulations provide steady hormone levels and typically result in fewer mood and energy fluctuations compared with injectable therapy.
Formulation Specific Considerations
Topical gels require several hours for adequate absorption before showering or bathing. Patches may cause mild to severe skin irritation, whereas injectable testosterone, typically dosed 50–400 mg intramuscularly every two to four weeks, may result in side effects including acne, fluid retention, mood changes, elevated red blood cells, and prostate enlargement.7 Serious risks can include hypertension, venous thromboembolism, sleep apnea, rare hepatotoxicity, cardiovascular events, testicular atrophy, and reduced sperm count.8 Symptom fluctuations may occur between injection intervals. Testosterone pellets, surgically implanted every three to six months, provide long-term hormone delivery. Buccal formulations are applied along the gumline above the upper teeth and absorbed into the bloodstream multiple times per day, which can occasionally cause gum irritation. Intranasal testosterone is administered into the nostrils several times daily, minimizing the risk of secondary exposure.
Oral and Compounded Testosterone
Historically, older oral testosterone formulations were avoided due to hepatotoxicity from rapid liver metabolism.9 Newer commercial oral formulations, such as testosterone undecanoate (Jatenzo, Tlando, Kyzatrex), are absorbed via the intestinal lymphatic system, bypassing the liver and achieving therapeutic levels with reduced liver risk.10-12 These medications are typically administered twice daily with food. Compounded testosterone offers additional flexibility, with typical doses ranging from 40 to 120 mg daily, often starting around 50 mg per day. Application sites include the shoulders, upper arms, inner thighs, or scrotum, with scrotal skin offering higher permeability and improved serum levels at lower doses. Proper counseling is essential to prevent transfer to partners or children. The choice of compounding base plays a critical role in absorption. For example, compounding pharmacies affiliated with PCCA have access to Atrevis™ Hydrogel, an advanced, alcohol-free, permeation-enhancing base for improved absorption and reduced irritation. Pentoxifylline at 5% can also be added to enhance microcirculation and absorption.
Contraindications
Contraindications to testosterone replacement therapy include prostate or breast cancer, pregnancy, severe liver, kidney, or cardiac disease, hypersensitivity, high hematocrit, and certain geriatric risks.13 Close laboratory monitoring is critical throughout therapy.
Erectile Dysfunction Therapies
In addition to testosterone replacement, erectile dysfunction therapies may be used alone or in combination with TRT. Compounding pharmacies provide unique dosage forms, custom strengths, and combination therapies that may include tadalafil, sildenafil, or apomorphine.14,15 These medications can be compounded individually, combined with one another, or formulated with oxytocin or L-arginine. Micro-dosing and fast-acting troches are also possible. Apomorphine, a dopamine agonist, can be used in cases of neurogenic ED, PDE-5 nonresponse, or intolerance to standard therapies and may be compounded with sildenafil or tadalafil in various oral dosage forms, including capsules, sublingual troches, or custom tablets.
Hair Loss, Acne, and Lifestyle Support
Compounded therapies also support hair loss and acne management in addition to hormone and ED treatment. Topical retinoids, benzoyl peroxide blends, and antibiotics can address acne, while minoxidil (topical or oral) and finasteride may treat alopecia or male pattern baldness. Lifestyle support is also important, as reducing excess body fat can lower aromatase activity and improve hormone balance.16 Beneficial micronutrients include magnesium, which supports free and total testosterone, vitamin D, which is linked to testosterone levels, and zinc, deficiency of which may impair testosterone production.17
Working with a Compounding Pharmacist
Working with a compounding pharmacist supports men’s health by providing personalized testosterone formulations, advanced absorption options, guidance on scrotal versus nonscrotal application, monitoring of PSA, hematocrit, and estradiol balance, customized ED therapies, and collaborative care with prescribers. The goal of individualized therapy is to optimize energy, libido, cognition, mood, muscle mass, and overall quality of life. Compounding pharmacies allow individualized therapy tailored to each patient’s needs, enhancing efficacy, safety, and overall quality of life for men managing hormone deficiencies and related health concerns.
Dr. Fatimah Hamade, PharmD, is a clinical pharmacist specializing in personalized, patient-centered compounding solutions at Rancho Compounding Pharmacy, where she collaborates closely with integrative and functional medicine practitioners to optimize therapeutic outcomes. With advanced training in sterile and non-sterile compounding, Dr. Hamade brings a deep expertise in hormone replacement therapy, dermatological preparations, pain management formulations, and individualized dosing strategies for complex or sensitive patient populations.
Known for her meticulous approach to formulation design and her commitment to evidence-based practice, Dr. Hamade plays a key role in bridging the gap between prescribers and pharmacy compounding teams. She frequently consults with naturopathic physicians, medical doctors, and other healthcare providers to ensure that each compounded medication meets the highest standards of safety, efficacy, and patient-specific customization.
References:
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