What are the benefits and risks of peptide therapy for patients with legitimate medical conditions, such as growth hormone deficiency or hypogonadism, and how should it be used under medical supervision?

Benefits and Risks of Peptide Therapy for Legitimate Medical Conditions

Growth Hormone Therapy for Growth Hormone Deficiency

For patients with confirmed growth hormone deficiency (GHD), somatropin (recombinant human growth hormone) provides substantial benefits in children and meaningful improvements in adults, but must be prescribed only by experienced physicians and requires careful patient selection and monitoring. 1

Pediatric GHD: Clear Benefits with Established Protocols

• Children with inadequate endogenous GH secretion should receive somatropin at 0.3 mg/kg/week divided into daily subcutaneous injections, with pubertal patients potentially requiring up to 0.7 mg/kg/week divided daily 1
• Treatment should continue until epiphyseal closure, as discontinuation at this point prevents further height gains 1
• For children in remission from Cushing disease who are GH deficient, prompt initiation of GH replacement is strongly recommended to maximize catch-up growth and achieve normal adult height, given the limited window of opportunity 2
• Dynamic testing for GH deficiency should be performed soon after definitive therapy in all children in remission from Cushing disease who have not completed linear growth 2

Adult GHD: Modest but Meaningful Benefits

• Adults with confirmed GHD experience reversal of many metabolic abnormalities and restoration of functional capacities toward normal when appropriately dosed 3
• GH replacement therapy in adults improves body composition, physical function, and quality of life, though effects are more modest than in children 3, 4
• Adult dosing should start conservatively at no more than 0.006 mg/kg daily, with gradual increases to a maximum of 0.025 mg/kg daily in patients ≤35 years 1
• Diagnosis requires an appropriate GH provocative test (such as insulin tolerance test) except in patients with multiple pituitary hormone deficiencies due to organic disease or congenital/genetic GHD 1

Critical Safety Monitoring Requirements

• Therapy must be supervised by a physician experienced in diagnosing and managing GHD, as improper use carries significant risks 1
• Response to therapy tends to decrease with time in pediatric patients; failure to increase growth rate during the first year suggests need for compliance assessment and evaluation of other causes including hypothyroidism, under-nutrition, and antibodies to recombinant human GH 1
• Most registries of adult GH replacement therapy have not shown increased incidence of cancers or cardiovascular morbidity/mortality, though some doubts remain about possible long-term risks 3

Testosterone Therapy for Hypogonadism

For men with confirmed biochemical hypogonadism (morning total testosterone <300 ng/dL on two separate occasions) and specific symptoms—particularly diminished libido and erectile dysfunction—testosterone replacement therapy provides small but significant improvements in sexual function, but offers little to no benefit for energy, physical function, or cognition. 5

Diagnostic Requirements Before Treatment

• Two separate morning total testosterone measurements (8-10 AM) below 300 ng/dL are required to establish hypogonadism, as single measurements are insufficient due to assay variability 5
• Free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG) should be measured, especially in men with obesity where total testosterone may be misleadingly low 5
• Serum LH and FSH must be measured to distinguish primary (testicular) from secondary (hypothalamic-pituitary) hypogonadism, which has critical treatment implications 5

Expected Benefits: Realistic Expectations

• Testosterone therapy produces small but significant improvements in sexual function and libido with a standardized mean difference of 0.35 5
• Little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition should be expected, even with confirmed hypogonadism 5
• Improvements in fasting plasma glucose, insulin resistance, triglyceride levels, and HDL cholesterol can occur with testosterone therapy 5
• Modest improvements in bone mineral density and correction of mild anemia may be seen 5

Treatment Selection and Monitoring

• Transdermal testosterone gel (40.5 mg daily) is the preferred first-line formulation due to more stable day-to-day testosterone levels compared to injections 5
• Intramuscular testosterone cypionate or enanthate (100-200 mg every 2 weeks) is a more economical alternative with annual cost of $156.24 versus $2,135.32 for transdermal preparations 5
• For injectable testosterone, measure levels midway between injections (days 5-7), targeting mid-normal values of 500-600 ng/dL 5
• Monitor hematocrit periodically and withhold treatment if >54%, as erythrocytosis is a significant risk, particularly with injectable forms 5
• Monitor PSA levels in men over 40 years, with urologic referral if PSA increases >1.0 ng/mL in first 6 months or >0.4 ng/mL per year thereafter 5

Absolute Contraindications

• Testosterone therapy is absolutely contraindicated in men actively seeking fertility, as it causes azoospermia by suppressing spermatogenesis 5
• For men with secondary hypogonadism desiring fertility preservation, gonadotropin therapy (hCG plus FSH) is mandatory instead of testosterone 5
• Active male breast cancer, hematocrit >54%, and untreated severe obstructive sleep apnea are absolute contraindications 5

Alternative: Clomiphene Citrate for Fertility Preservation

• Clomiphene citrate (25-50 mg three times weekly) is an effective alternative for men with secondary hypogonadism who wish to preserve fertility, as it stimulates endogenous testosterone production without suppressing spermatogenesis 6
• Clomiphene achieves similar or superior outcomes for sexual function and quality of life while preserving fertility, making it particularly valuable for younger men 6
• Switch to testosterone replacement if clomiphene fails after 3 months or if fertility preservation is no longer a concern 6

GLP-2 Analog (Teduglutide) for Short Bowel Syndrome

For carefully selected patients with chronic intestinal failure due to short bowel syndrome, teduglutide (GLP-2 analog) is the first-choice growth factor treatment, but should only be prescribed by experts experienced in managing these complex patients. 2

Benefits and Limitations

• Teduglutide mainly increases intestinal wet weight absorption and decreases the need for parenteral fluid support in SBS patients with intestinal failure 2
• Effects on energy absorption are less predominant compared to fluid absorption 2
• Benefits are seen in both categories of SBS patients—those with and without a colon in continuity 2
• Effects quickly decrease and vanish after stopping treatment, requiring life-long therapy 2

Patient Selection and Informed Consent

• Patients must be carefully informed of potential benefits and risks, including probability of reducing or weaning from home parenteral nutrition, probability of quality of life improvement, expected duration of treatment, expected effects after cessation, potential adverse effects, and cost-effectiveness 2
• Efficacy should be evaluated according to standardized protocols measuring fluids, electrolytes, and energy balance whenever possible 2
• Careful long-term monitoring is required as potential long-term complications are unknown given the still-low number of treated patients 2

Comparison with Growth Hormone

• Teduglutide is preferred over growth hormone (somatotropin) for SBS patients due to lower frequency of adverse effects 2
• High-dose growth hormone may have positive effects on intestinal wet-weight absorption but is often associated with significant side effects, while low-dose growth hormone has fewer side effects but effects may be partly due to stimulatory effect on oral energy intake 2
• Adverse events with teduglutide are mainly localized to the gastrointestinal tract, whereas growth hormone causes mainly systemic adverse events that appear more frequently 2

Critical Pitfalls to Avoid Across All Peptide Therapies

• Never prescribe testosterone to eugonadal men (normal testosterone levels), even for weight loss, cardiometabolic improvement, cognition, vitality, or physical strength, as this violates evidence-based guidelines 5
• Never diagnose hypogonadism based on symptoms alone without confirmed biochemical testing, as symptoms are non-specific 5
• Never start testosterone without confirming the patient does not desire fertility, as this causes irreversible suppression of spermatogenesis 5
• Never prescribe growth factors for intestinal rehabilitation outside of expert centers, as these treatments require specialized knowledge for proper patient selection, monitoring, and management of complications 2
• Never expect dramatic improvements in energy, physical function, or cognition from testosterone therapy, as even in confirmed hypogonadism these benefits are minimal to absent 5