Management of Erythrocytosis in Men Receiving TRT

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Management of Erythrocytosis in Men Receiving Testosterone Therapy: Clinical Consultation Guide (2022)
Pranjal Agrawal, Sajya M. Singh, Taylor Kohn

1. Introduction

Testosterone deficiency, previously known as male hypogonadism, affects approximately 25% of all men, with a prevalence that increases with age [1]. Risk factors for developing adult-onset testosterone deficiency include obesity, chronic disease, and poor general health [2]. Individuals with clinical hypogonadal symptoms and two-morning samples demonstrating low testosterone levels often benefit from testosterone therapy (TT).

The European Association of Urology (EAU) lists the following as primary indications for TT: delayed puberty; Klinefelter’s syndrome with hypogonadism; sexual dysfunction, including erectile dysfunction not responding to phosphodiesterase-5 inhibitors (PDE5i); osteoporosis due to hypogonadism; hypopituitarism; and adult men with testosterone levels lower than an age-specific physiological range exhibiting hypogonadal symptoms [3,4]. The primary aim of TT is to reduce clinical symptoms of testosterone deficiency by restoring serum testosterone levels to an age-dependent mid-normal range [3,4].

However, TT can lead to adverse effects, including, most commonly, erythrocytosis or an increase in hemoglobin (Hb) and hematocrit (Hct) levels [3,4].
A recent study demonstrated that erythrocytosis in men on TT is an independent risk factor for major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) within the first year of treatment onset [5]. In fact, the EAU lists Hct >54% as a contraindication for TT [3,4]. Low testosterone levels have been associated with an unfavorable prognosis for prostate cancer, although this association is still a matter of debate [6]. Therefore, the benefits of TT must be weighed against the higher cardiovascular risk associated with the initiation of therapy. Furthermore, any development of erythrocytosis while on TT must be promptly identified and managed.

high hematocrit dangers.jpg

2. Does the TT route, duration, or dosage matter?

3. Management of erythrocytosis

4. Conclusions

Erythrocytosis is the most common side effect of all TT modalities. Patient-specific factors should be considered when choosing an appropriate TT dosage and modality. Owing to the risk of MACE and VTE, Hct >54% should prompt providers to consider decreasing and discontinuing TT until normalization of Hct.


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Take-home points

*the clinical significance of a hematocrit >54% is unknown

*Although it is not yet clear what upper limit of hematocrit level is clinically desirable, dose adjustments may be necessary to keep hematocrit below 52–54%


*Some authors recommend that TTh be discontinued if hematocrit is >54%, which may be reasonable while baseline hematocrit level >50% is a relative contraindication for starting testosterone therapy. However, these recommendations are based on assumptions – the clinical significance of a hematocrit >54% is unknown

*The lack of increase in cardiovascular events with elevated hematocrit may be due to the fact that T acts as a vasodilator and has anti-atherosclerotic effects [223]. In addition, testosterone is able to decrease plasma concentrations of procoagulatory substances such as fibrinogen and PAI-1 as well as Factor XII [224] Isolated hematocrit elevations can be the result of insufficient fluid intake on a hot day. Only repeated measures of hematocrit >54% should be followed by concomitant administration of aspirin, bleeding, therapeutic phlebotomy, and/or discontinuation of TTh until hematocrit declines below 54%. After normalization of hematocrit levels, TTh can be continued with a reduced dosage

*Periodic hematological assessment is, however, indicated, i.e. before TTh, then 3–4 months and 12 months in the first year of treatment, and annually thereafter. Although it is not yet clear what upper limit of hematocrit level is clinically desirable, dose adjustments may be necessary to keep hematocrit below 52–54%

*Men with significant erythrocytosis (hematocrit >52%), severe untreated obstructive sleep apnea, or untreated severe congestive heart failure should not be started on treatment with TTh without prior resolution of the co-morbid condition

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