Management of male obesity-related secondary hypogonadism: A clinical update

Table 1 Characteristics of available testosterone formulations

Formulation	Available strengths	Dose regimen	Advantage	Formulation-specific adverse effects	Monitoring frequency
Parenteral preparations
Testosterone enanthate	50, 75, 100 mg in 0.5 mL and 200 mg in 1.0 mL sesame oil	Start with 75 mg weekly subcutaneous/intramuscular injections and up-titrate dose to reach target T	Relatively inexpensive, flexible dosing	Pain of injections; fluctuations in symptoms due to peaks and troughs in serum T	50, 75, 100 mg in 0.5 mL and 200 mg in 1 mL sesame oil
Testosterone cypionate	100 and 200 mg/mL in cottonseed oil	Deep intramuscular injection to gluteal muscles once in 2 wk or subcutaneous injections in abdominal adipose tissue weekly		Pain of injections. Fluctuations in symptoms due to peaks and troughs in serum T	50, 75, 100 mg in 0.5 mL and 200 mg in 1.0 mL sesame oil
Testosterone undecanoate	750 mg/3 mL in castor oil	Start with 750 mg deep intramuscular injection deep in the gluteal muscle repeat after 4 wk and then every 10 wk	Infrequent administration	Painful, large-volume intramuscular injection; some report coughing immediately after injection. Possible risk of pulmonary oil micro-embolism	750 mg/3 mL in castor oil
Implants
Testosterone pellets	75 mg/pellet	Inserted subcutaneously into fat in the hip area; 2 to 6 months will last 3 to 4 months; 6-10 implants last for 4-6 months	Infrequent administration	A surgical incision is required for insertions; local hematoma and infection; spontaneous extrusion of pellets	Measure T concentrations at the end of the dosing interval; adjust the number of pellets and/or dosing interval to maintain serum T concentrations in the mid-normal range
Topical/transdermal
Testosterone patch	2 or 4 mg patches daily	4 mg starting dose, to be applied to back, abdomen, and upper arms. Do not apply the patch to the same area within 7 d	Easy application	Serum T concentrations are sometimes in the low-normal range. May need applications of two patches daily. Skin irritation at the application site	Assess serum T 3-12 h after application; adjust the dose to achieve T levels in the mid-normal range
Testosterone gel	1.00% gel-50 to 100 mg T/d	25-50 mg T packets to apply to the shoulder or upper arms; 20.25 mg T per 1 pump actuation, or a 20.25 mg packet	Flexibility of dosing; easy application; good skin tolerability; less erythrocytosis	Potential of contact transfer to female partners or children; skin irritation in some	Assess serum T 2-8 h following gel application, after the patient has been on treatment for at least 1 wk; adjust the dose to achieve serum T in the mid-normal range
	1.62% gel-40.5 to 81 mg T/d	40.5 mg T. 2 pump actuation or a 40.5 g packet; apply to shoulders or upper arms
	2.00% gel 10 mg/0.5 g per pump actuation	40.0 mg (4 pump actuation)/d starting dose; apply to inner thighs
	2.00% lotion 30 mg/pump actuation	Start with 60 mg, apply to axilla	Good skin tolerability	Potential of contact transfer to female partners or children. Dripping/wet sensation in the axilla
Buccal/nasal
Buccal tablets	30 mg twice/d	Apply to gums	Convenience and discreet	Gum-related adverse events; dislodgment
Nasal gel	11 mg gel intranasal two or three times daily	Start with one actuation (5.5 mg) into each nostril-a total of 11 mg; apply to nose three times daily	Rapid absorption and avoidance of first-pass metabolism	Multiple daily intranasal dosing; local nasal irritation; not appropriate for men with nasal disorders
Oral
Testosterone undecanoate capsules	40 mg capsules 2-3 times daily. 158 to 396 mg twice daily	80 to 120 mg/d. Start with 237 mg twice a day with food	Convenience of oral administration	Variable response; must be administered along with a fatty meal; fat content of meals may increase bioavailability	Monitor serum T 3-5 h after ingestion of the tablet

T: Testosterone.

Table 2 Cautions with testosterone replacement therapy and monitoring for adverse effects

High-risk population for TRT	Special considerations in monitoring
Very high risk of serious outcomes: prostate cancer; breast cancer	For patients who opt for prostate monitoring: Men aged 55-69 yr & those aged 40-69 yr who are at increased risk for prostate cancer and choose monitoring; perform DRE and measure PSA at baseline, at 3-12 months after starting treatment, and then as per local prostate cancer screening guidelines
Moderate to high risk of adverse outcomes	Urologic consultation should be sought if: (1) Increase in serum PSA > 1.4 ng/mL within 12 months of starting TRT; (2) PSA > 4 ng/mL at any time; (3) DRE detected new onset prostate abnormality; and (4) significant worsening of LUTS
Unevaluated prostate nodule or induration	To check Haematocrit at baseline, then at 3-6 months following TRT, and then annually. If Hct > 54%, stop therapy until it decreases to a safer level; evaluate for other causes of erythrocytosis (sleep apnoea, COPD), re-initiate at lower doses when Hct falls below normal
Baseline PSA > 4 ng/mL or > 3 ng/mL in men at high risk for prostate cancer
Severe lower urinary tract symptoms
Haematocrit > 48% (> 50% for men living at high altitudes)
Uncontrolled or poorly controlled heart failure
Myocardial infarction or stroke in the preceding 6 months
Untreated severe obstructive sleep apnoea
Wants fertility in the near future
Formulation-specific adverse effects (Table 1)

TRT: Testosterone replacement therapy; PSA: Prostate specific antigen; DRE: Digital rectal examination; Hct: Haematocrit; COPD: Chronic obstructive pulmonary disease; LUTS: Lower urinary tract symptoms.