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Testosterone Cypionate and Autoimmune Disease: What Clinicians and Patients Need to Know

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At a glance

  • Approved use / Hypogonadism in men; not autoimmune disease [1]
  • Autoimmune treatment evidence / One 10-man pilot study of testosterone gel in relapsing-remitting MS [2]
  • Label contraindication / Serious cardiac, hepatic or renal disease (Depo-Testosterone) [1]
  • Blood pressure / All testosterone products can raise blood pressure [3]
  • Hematocrit / Intramuscular cypionate/enanthate raised mean hematocrit 4.0% vs placebo [4]
  • Anticoagulants / Androgens may increase sensitivity; dose may need reduction [1]
  • Corticosteroids / May increase fluid retention [1]
  • Label dose / 50 to 400 mg IM every 2 to 4 weeks [1]

What is the direct answer?

Testosterone cypionate is approved for replacement in men with primary or hypogonadotropic hypogonadism [1]. Autoimmune disease is not an approved use. The 2007 MS pilot study does not establish a role for testosterone in MS or any other autoimmune disease [2].

What does the Depo-Testosterone label say?

The label contraindicates known hypersensitivity, breast cancer in men, known or suspected prostate cancer, pregnancy, and serious cardiac, hepatic or renal disease [1]. It warns that edema, with or without heart failure, may be a serious complication in patients with pre-existing cardiac, renal or hepatic disease [1]. It reports venous thromboembolism and says to stop if a VTE is suspected [1]. Testosterone can increase blood pressure, and the label says testosterone products are not recommended in uncontrolled hypertension [1]. The label says to check hemoglobin and hematocrit periodically in long-term use [1]. Prolonged high doses of androgens, principally 17-alpha-alkyl androgens, have been associated with hepatic adenomas, hepatocellular carcinoma and peliosis hepatis [1]. Autoimmune disease is not named in the label's indications or contraindications [1].

What is known about testosterone and autoimmunity?

A 2018 review on sex hormones in acquired immunity and autoimmune disease notes that innate and adaptive immune cells bear receptors for sex hormones and respond to hormonal cues; the review focuses on estrogen and systemic lupus erythematosus (SLE) [5]. A 1987 study measured plasma androgens in 5 men and 42 women with SLE. Women with SLE had decreased levels of all androgens, and the lowest levels were in women with active disease [6]. Neither the review nor the 1987 study tested testosterone treatment.

What did the multiple sclerosis trial show?

Sicotte et al. studied 10 men with relapsing-remitting MS in a crossover design: 6 months of pretreatment, then 12 months of daily 10 g gel containing 100 mg testosterone. Cognitive performance improved (P=.008) and brain atrophy slowed (P<.001). Gadolinium-enhancing lesion numbers (P=.31) and volumes (P=.94) did not change significantly. Lean body mass increased (P=.02) [2]. The authors called the findings exploratory.

What monitoring and interactions matter?

The label says to confirm hypogonadism with morning serum testosterone on at least two separate days, both below the normal range [1]. The replacement dose is 50 to 400 mg intramuscularly every 2 to 4 weeks [1]. The label says to monitor blood pressure periodically [1]. A 2022 network meta-analysis of 29 placebo-controlled trials in 3,393 men found intramuscular enanthate/cypionate raised mean hematocrit by 4.0% (95% CI 2.9 to 5.1) versus placebo [4]. Testosterone used with corticosteroids or ACTH may increase fluid retention, especially in people with heart, kidney, or liver disease [1]. Androgens may increase sensitivity to oral anticoagulants, and the anticoagulant dose may need to be reduced to maintain satisfactory anticoagulation [1]. Androgens may lower blood glucose and insulin requirements [1]. TRAVERSE, a 5,246-man cardiovascular safety trial in men with hypogonadism, tested daily 1.62% testosterone gel, not injections, and was not an autoimmune study [7].

Frequently asked questions

Does testosterone cypionate treat autoimmune disease?
It is approved for hypogonadism in men, not autoimmune disease [1]. One small trial in 10 men with relapsing-remitting MS used testosterone gel [2].
Can testosterone cypionate cause an autoimmune flare?
The adverse reactions listed in the Depo-Testosterone label do not include autoimmune flares. The label lists reactions such as edema, polycythemia and venous thromboembolism, and warns that testosterone can increase blood pressure [1].
What does lupus research say about testosterone?
A 1987 study found low plasma androgens in women with SLE, with the lowest levels in women with active disease. It measured hormone levels and did not test testosterone treatment [6].
What interactions matter with prednisone or warfarin?
Testosterone used with corticosteroids or ACTH may increase fluid retention, especially in people with heart, kidney, or liver disease [1]. Androgens may increase sensitivity to oral anticoagulants, and the anticoagulant dose may need to be reduced to maintain satisfactory anticoagulation [1].
What monitoring does the label recommend?
The Depo-Testosterone label recommends confirming hypogonadism with morning serum testosterone measurements on at least two separate days below the normal range, checking hemoglobin and hematocrit periodically during long-term use, monitoring blood pressure periodically, and using 50 to 400 mg intramuscularly every 2 to 4 weeks [1].

References

  1. U.S. National Library of Medicine, DailyMed. Depo-Testosterone (cypionate) intramuscular, Pharmacia & Upjohn/Pfizer (testosterone cypionate) prescribing information. Depo-Testosterone (cypionate) intramuscular, Pharmacia & Upjohn/Pfizer (testosterone cypionate) label
  2. Sicotte NL, Giesser BS, Tandon V, Klutch R, Steiner B, Drain AE, et al. Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol. 2007;64(5):683-8. Testosterone treatment in multiple sclerosis: a pilot study
  3. FDA issues class-wide labeling changes for testosterone products | FDA. FDA issues class-wide labeling changes for testosterone products | FDA
  4. Nackeeran S, Kohn T, Gonzalez D, White J, Ory J, Ramasamy R. The Effect of Route of Testosterone on Changes in Hematocrit: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Trials. J Urol. 2022;207(1):44-51. The Effect of Route of Testosterone on Changes in Hematocrit: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Trials
  5. Moulton VR. Sex Hormones in Acquired Immunity and Autoimmune Disease. Front Immunol. 2018;9:2279. Sex Hormones in Acquired Immunity and Autoimmune Disease
  6. Lahita RG, Bradlow HL, Ginzler E, Pang S, New M. Low plasma androgens in women with systemic lupus erythematosus. Arthritis Rheum. 1987;30(3):241-8. Low plasma androgens in women with systemic lupus erythematosus
  7. Lincoff AM, Bhasin S, Flevaris P, Mitchell LM, Basaria S, Boden WE, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;389(2):107-117. Cardiovascular Safety of Testosterone-Replacement Therapy
Evidence overview for Testosterone Cypionate and Autoimmune Disease: What Clinicians and Patients Need to Know