In trans persons on gender-affirming hormonal treatment, a decrease (in trans women) or increase (in trans men) in hematocrit is often observed. Reference ranges for evaluation of hematocrit levels in trans persons have not been established. This prospective cohort study is part of the European Network for the Investigation of Gender Incongruence (ENIGI). At the Ghent and Amsterdam sites, we included 625 hormone-naïve trans persons. Gender-affirming hormonal treatment was initiated at the first visit. In trans men, serum hematocrit (Hct) levels increased during the first year (+4.9 Hct %, 95% CI 3.82-5.25), with the most pronounced increase during the first 3 months (+2.7 Hct %, 95% CI 1.94-3.29). Trans men receiving testosterone esters had a larger increase in serum hematocrit levels compared to trans men receiving testosterone undecanoate (Δ 0.8 Hct %). Of 192 trans men, 22 (11.5%) developed serum hematocrit levels ≥50.0%. Trans men on testosterone undecanoate were less likely to develop hematocrit levels ≥50% or ≥52%, compared to trans men on testosterone esters, and were less likely to develop hematocrit levels ≥50%, compared to trans men on testosterone gel. In trans women, serum hematocrit had dropped by 4.1 Hct % (95% CI 3.50-4.37) after 3 months, after which only small decreases were observed. In conclusion, serum hematocrit levels can be found in the reference range of the perceived gender as from 3 months after the initiation of gender-affirming hormonal treatment.

Context Erythrocytosis is a known side effect of testosterone therapy that can increase the risk of thromboembolic events. Objectives To study the prevalence and determinants in the development of erythrocytosis in trans men using testosterone. Design A twenty year follow-up study in adult trans men who started testosterone therapy, and had monitoring of hematocrit at our center (n=1073). Results Erythrocytosis occurred in 11% (hematocrit>0.50 l/l), 3.7% (hematocrit>0.52 l/l) and 0.5% (hematocrit>0.54 l/l) of trans men. Tobacco use (OR 2.2, 95%CI 1.6-3.3), long-acting undecanoate injections (OR 2.9, 95%CI 1.7-5.0), age at initiation of hormone therapy (OR 5.9, 95%CI 2.8-12.3), BMI (OR 3.7, 95%CI 2.2-6.2) and pulmonary conditions associated with erythrocytosis and polycythemia vera (OR 2.5, 95%CI 1.4-4.4) were associated with hematocrit >0.50 l/l. In the first year of testosterone therapy hematocrit increased most: 0.39 l/l at baseline to 0.45 l/l after 1 year. Although there was only a slight continuation of this increase in the following 20 years, the probability of developing erythrocytosis still increased (10% after 1 year, 38% after 10 years). Conclusion Erythrocytosis occurs in trans men using testosterone. The largest increase in hematocrit was seen in the first year, but also after the first years there is a substantial number of people that present with hematocrit >0.50 l/l. A reasonable first step in the care for trans men with erythrocytosis while on testosterone is to advise them to quit smoking and to switch to a transdermal administration route and if BMI is high, to lose weight.

Vital biological processes, such as trafficking, sensing, and motility, are facilitated by cellular lipid membranes, which interact mechanically with surrounding fluids. Such lipid membranes are only a few nanometers thick and composed of a liquid crystalline structure known as the lipid bilayer. Here, we introduce an active, noncontact, two-point microrheology technique combining multiple optical tweezers probes with planar freestanding lipid bilayers accessible on both sides. We use the method to quantify both fluid slip close to the bilayer surface and transmission of fluid flow across the structure, and we use numerical simulations to determine the monolayer viscosity and the intermonolayer friction. We find that these physical properties are highly dependent on the molecular structure of the lipids in the bilayer. We compare ordered-phase with liquid disordered-phase lipid bilayers, and we find the ordered-phase bilayers to be 10 to 100 times more viscous but with 100 times less intermonolayer friction. When a local shear is applied by the optical tweezers, the ultralow intermonolayer friction results in full slip of the two leaflets relative to each other and as a consequence, no shear transmission across the membrane. Our study sheds light on the physical principles governing the transfer of shear forces by and through lipid membranes, which underpin cell behavior and homeostasis.

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