Veedma Health Blog

Blood pressure rise ranks first; track hematocrit and PSA on a schedule, set action thresholds, and fix problems early with dose or formulation changes.

The relationship

Testosterone replacement therapy is treatment that raises low testosterone into a healthy range to relieve symptoms such as low energy, libido loss, and decreased strength [1,2]. The upside is real, but so are a few predictable testosterone side effects, led by blood pressure increases and red-cell elevation that can thicken the blood [1,3–5].

In a large 2023 cardiovascular safety trial, major cardiac events were not higher on therapy versus placebo, but ambulatory blood pressure rose modestly, underscoring why routine BP checks matter [3,4]. Ambulatory systolic BP increases around 1–3 mmHg have been recorded with some oral formulations, with larger rises in men already on antihypertensives [4].

Another common, dose-related effect is a rise in hematocrit—the percentage of blood that is red cells. Excessive hematocrit (also called erythrocytosis) raises viscosity and can increase thrombotic risk; short-acting injections carry the highest incidence, while transdermals are lower [5,6].

How it works

1) Blood pressure and fluid balance

Testosterone can expand plasma volume and interact with vascular tone, producing small mean rises in ambulatory systolic pressure; in a 155-man study of oral testosterone undecanoate, 24-hour systolic BP increased 1.7–1.8 mmHg at 120–180 days, with larger changes in men already treated for hypertension [4]. Hypertension is defined as ≥130/80 mmHg per ACC/AHA, which is the level where most clinicians start or intensify therapy if overall risk warrants it [7].

2) Red-cell mass and hematocrit

Androgens stimulate erythropoiesis via erythropoietin signaling and hepcidin suppression, raising hematocrit; risk is highest with short-acting injectables and higher doses [5]. Practical action thresholds used in guidelines: reduce dose, switch to a non-injectable, or hold therapy if hematocrit reaches 54% or higher, then resume at a lower dose once corrected [1].

3) Estradiol conversion and breast tissue

Aromatization is the enzyme conversion of testosterone to estradiol. Estradiol supports libido, fat regulation, and bone, but excess can contribute to breast tenderness or gynecomastia in some men on higher doses; estradiol also mediates part of testosterone’s metabolic effects [10,11].

4) HPT axis suppression and fertility

Exogenous testosterone suppresses hypothalamic GnRH and pituitary LH/FSH, lowering intratesticular testosterone and impairing spermatogenesis; this is the mechanism behind testosterone’s contraceptive effect and why TRT is avoided when near-term fertility is a goal [15]. Recovery after stopping is typical but variable and can take months [15].

5) Sleep and breathing

Short-term or higher-dose testosterone can transiently worsen obstructive sleep apnea severity in predisposed men, with effects that may lessen by 18 weeks, likely through chemoreflex changes [8,9]. Screening is sensible when snoring, witnessed apneas, or daytime sleepiness are present [1].

Diagnostic thresholds, when symptoms persist: Meta-analyses and major guidelines support starting decisions around total testosterone ≤350 ng/dL (≈12 nmol/L) or free testosterone ≤100 pg/mL (≈10 ng/dL); confirm with two morning tests and assess symptoms before treatment [2,11].

Conditions linked to it

• Hypertension on TRT: Small average BP rises can still matter at a population level. Treat per guideline if readings are consistently ≥130/80 mmHg, and adjust TRT if BP proves dose-responsive [4,7].
• Hematocrit increase: Dose-dependent; highest with short-acting injections. Aim to keep hematocrit under 52%, and act if it reaches 54% (dose reduction, switch to gel/patch, or therapeutic phlebotomy in select cases) [1,5].
• Estradiol increase on TRT: May present with nipple tenderness or gynecomastia. Most cases improve with dose/formulation changes; medication options are off-label and reserved for select patients after risk–benefit review [10,11].
• Fertility on TRT: Suppressed LH/FSH can lower sperm counts to contraceptive levels; use alternatives if family planning is active [15].
• Prostate monitoring: PSA typically rises modestly; refer if PSA increases more than 1.4 ng/mL in 12 months or exceeds 4.0 ng/mL during the first year, per Endocrine Society guidance [1,12–14].

Limitations: Most BP and hematocrit data are formulation-specific or from studies not powered for rare events; OSA effects are time-dependent and heterogeneous across trials [4,8,9].

Symptoms and signals

• Rising home or clinic BP readings week to week.
• Headache, flushing, or new ankle swelling.
• Facial redness, thicker-feeling blood draws, or frequent nosebleeds when hematocrit is high.
• Nipple soreness or visible breast tissue growth.
• Louder snoring, witnessed apneas, or daytime sleepiness.
• Fertility concerns: low volume or delayed conception after starting TRT.
• PSA increase on lab reports compared with baseline.

What to do about it

1. Test on a schedule. Before starting: morning total testosterone (twice), consider free testosterone, CBC for hematocrit, PSA and digital rectal exam if age-appropriate, baseline BP (home and office). Recheck at 3 months, 6–12 months, then yearly: testosterone level for dosing, hematocrit, PSA, and BP; sooner if symptoms appear [1,2].
2. Fix the issue at the right lever.
   • Hypertension on TRT: Confirm with 7-day home BP average. Start or intensify standard therapy and tighten sodium, sleep, weight, and alcohol inputs; if BP tracks the dose, lower or switch formulation [4,7].
   • Hematocrit increase: Reduce dose, lengthen dosing interval, or switch to gel/patch. Consider temporary hold at ≥54%; therapeutic phlebotomy is an option if needed while re-titrating [1,5].
   • E2-related breast symptoms: First step is dose/formulation change. Off-label short courses of tamoxifen can help selected, persistent cases after shared decision-making; evidence exists but is not robust for routine use [10,18,22].
   • Apnea and TRT: Screen when snoring/daytime sleepiness exist; if positive, treat OSA (e.g., CPAP) and reassess TRT dosing [8,9].
   • Fertility on TRT: If near-term conception is a goal, stop TRT and consider alternatives such as clomiphene citrate or hCG-based regimens under specialist care [15].
3. Monitor and document. Keep a simple log: weekly home BP average, dosing changes, hematocrit, PSA, and symptoms. Adjust in small steps and re-test within 6–8 weeks after changes [1,7].

Myth vs Fact

• Myth: “If my BP rises a little, it does not matter.” Fact: Small sustained increases raise long-term risk; treat to guideline targets while optimizing TRT [4,7].
• Myth: “Gynecomastia always means estradiol is ‘too high.’” Fact: Dose and tissue sensitivity both matter; many cases resolve with dose/formulation changes [10,11].
• Myth: “TRT is fine if I am trying to conceive.” Fact: TRT suppresses sperm production; use fertility-preserving alternatives [15].
• Myth: “Erythrocytosis is rare and harmless.” Fact: It is among the most common lab issues and can increase thrombotic risk; act at defined hematocrit thresholds [5,6].

Bottom line

TRT can restore quality of life when used for the right patient and dose. The main actionable side effects are blood pressure rise and hematocrit increase; estradiol symptoms, sleep apnea interactions, prostate monitoring, and fertility planning round out the list. Measure, set thresholds, adjust early, and work with a clinician who follows evidence-based labs and blood pressure care [1,3–5,7].