Testosterone Cypionate: What to Expect Week by Week in Your First Month

What happens after a shot?

Testosterone cypionate is a testosterone ester dissolved in oil. Injected deep into the gluteal muscle, it is absorbed slowly from that oil, so a dose lasts days rather than hours [1]. The Depo-Testosterone label gives a half-life of about 8 days after intramuscular injection, approves 50 to 400 mg every 2 to 4 weeks, and states the product is for deep gluteal intramuscular use only, never intravenous [1]. Injection site pain and inflammation are listed reactions [1].

Changes testosterone can cause

FDA's February 2025 action followed ambulatory blood pressure studies that confirmed a rise with all testosterone products, class-wide [2]. The Depo-Testosterone label says testosterone can increase blood pressure, that blood pressure should be monitored periodically, especially in men with hypertension, and that these products are not recommended in men with uncontrolled hypertension [1].

Hematocrit is the other signal with numbers. Intramuscular enanthate or cypionate raised mean hematocrit 4.0% (95% CI 2.9 to 5.1) versus placebo in a network meta-analysis of 29 placebo-controlled randomized trials of all testosterone formulations [3]. A review reports that short-acting injectables have the highest incidence of erythrocytosis [5]. The Endocrine Society recommends monitoring symptoms, serum testosterone, hematocrit and prostate cancer risk during the first year [6].

Possible reactions the label lists

The label states that exogenous androgens inhibit pituitary luteinizing hormone (LH) and, at large doses, follicle-stimulating hormone (FSH), which suppresses sperm production [1]. Its listed adverse reactions include acne, seborrhea, gynecomastia, fluid retention, libido changes, headache, anxiety, depression and polycythemia [1]. Gynecomastia may develop and occasionally persists [1]. Most gynecomastia results from deficient androgen action or excessive estrogen action in breast tissue, and testosterone is converted to estradiol by aromatase [7][8]. In a randomized crossover study of 17 healthy men over 60, three weekly high-dose injections of testosterone esters worsened breathing during sleep, adding about seven respiratory disturbance events per hour [9].

What the trials actually measured

The Testosterone Trials gave testosterone gel or placebo for one year to 790 men aged 65 or older with testosterone below 275 ng/dL and reported results after that year: more sexual activity (P<0.001), more sexual desire and erectile function, no significant benefit on the FACIT-Fatigue vitality scale, and slightly better mood [4]. TRAVERSE randomized 5,246 men aged 45 to 80 with cardiovascular disease or high risk of it to 1.62% testosterone gel or placebo. Major adverse cardiovascular events were 7.0% versus 7.3% (hazard ratio 0.96, 95% CI 0.78 to 1.17) over a mean follow-up of 33 months [10]. Both trials used gel, not injections [4][10].

Before the first injection

The label says the diagnosis should be confirmed with morning serum testosterone measured on at least two separate days, both below the normal range, and that dose is adjusted to the patient's response and the appearance of adverse reactions [1]. The Endocrine Society guideline recommends against starting testosterone therapy in men planning fertility in the near term [6].

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