Testosterone Cypionate: Restarting After Acute Illness

Is there a standard restart schedule?

The Depo-Testosterone label gives 50 to 400 mg every 2 to 4 weeks for hypogonadal men and an intramuscular half-life of about 8 days [1]. This is the dosing for routine replacement.

What in the label matters after a serious illness?

The label contraindicates use in patients with serious cardiac, hepatic or renal disease [1]. The label also warns that venous thromboembolism, including deep vein thrombosis and pulmonary embolism, has been reported with testosterone products [1]. It says to evaluate lower-extremity pain, edema, warmth and erythema for DVT and acute shortness of breath for PE, and to discontinue if a VTE is suspected [1].

The label warns that edema, with or without congestive heart failure, may be serious in men with pre-existing cardiac, renal or hepatic disease [1]. It warns that hypercalcemia may occur in immobilized patients and says to discontinue the drug if it occurs [1]. Blood pressure is a class effect: FDA says ambulatory blood pressure studies confirmed an increase with all testosterone products [2]. The label says testosterone can raise blood pressure and is not recommended in uncontrolled hypertension [1].

What do we know about hematocrit?

In a network meta-analysis of 29 placebo-controlled trials and 3,393 men, covering several testosterone formulations, intramuscular testosterone enanthate/cypionate raised mean hematocrit by 4.0% (95% CI 2.9 to 5.1) versus placebo [3]. A retrospective review of 178 hypogonadal men found hematocrit above 50% in 66.7% of men on injectable testosterone, 12.8% on gels and 35.1% on pellets over 3 years. The injection group was younger and had higher baseline hematocrit, and the study was not randomized [6]. The Depo-Testosterone label lists polycythemia as an adverse reaction [1].

The Endocrine Society guideline recommends against starting testosterone in men with elevated hematocrit, untreated severe sleep apnea, uncontrolled heart failure, or myocardial infarction or stroke within 6 months [4]. Those recommendations address starting therapy.

Does TRAVERSE apply to cypionate injections?

TRAVERSE was a randomized, double-blind, placebo-controlled noninferiority trial in 5,246 men aged 45 to 80 with hypogonadism and existing or high cardiovascular risk [5]. It tested daily 1.62% testosterone gel, not cypionate injections [5]. Major adverse cardiovascular events occurred in 7.0% on testosterone gel and 7.3% on placebo, with a hazard ratio of 0.96 (95% CI 0.78 to 1.17), meeting noninferiority [5]. Because the trial used gel, its result does not directly answer the question for injections.

The Depo-Testosterone label still carries older language that long-term safety trials have not been conducted, that studies have been inconclusive for major adverse cardiovascular events, and that some but not all studies reported an increased risk. It also carries the blood pressure warning [1].

What about warfarin and other medicines?

The label says androgens may increase sensitivity to oral anticoagulants, the anticoagulant dose may need to be reduced, and INR and prothrombin time should be monitored more often when starting or stopping testosterone [1]. It says androgens may lower blood glucose and insulin requirements in diabetic patients [1].