Updated retrospective and prospective studies transgender individuals receiving GAHT and risk of venous thrombosis
| Study . | Patient demographics . | Study type . | Results . | Interpretation . |
|---|---|---|---|---|
| Manchkanti et al (2023)25 | N = 12 369 transgender individuals | Retrospective observational | The transgender individuals receiving estrogen had a lower incidence of cerebral infarcts (0.21% vs. 0.42%, P = .0003) and a moderately decreased incidence of MI (0.14% vs 0.22%, P = .062) compared to cisgender women. | The study observed decreases in rates of thrombotic events, acute MI, and cerebral infarction in transgender individuals receiving estrogen compared to cisgender women. |
| Mullins et al (2021)48 | N = 611 | Retrospective observational | Among 611 participants, 28.8% were transgender individuals receiving estrogen and 68.1% were transgender individuals receiving testosterone. The median age was 17 years at GAHT initiation. 5 individuals were treated with anticoagulation during GAHT: 2 with a previous thrombosis and 3 for prophylaxis. No participant developed thrombosis while on GAHT. | The findings suggest that, in youth, GAHT titrated within physiologic range does not carry a significant risk of thrombosis in the short-term. |
| Kozato et al (2021)41 | N = 407 | Retrospective observational | 407 transgender individuals receiving estrogen undergoing primary vaginoplasty. Of all cases, 1 patient presented with VTE from the cohort whose estrogen was suspended prior to surgery. No VTE events were noted among those who continued. | Perioperative VTE was not a significant risk in a large, homogenously treated cohort of transgender individuals, independent of whether estrogen was suspended prior to surgery. |
| Scheres et al (2021)5 | N = 198 | Prospective observational | Transgender individuals on estrogen GAHT developed increased factors IX and XI as well as a decrease in protein C. | In transgender individuals receiving estrogen, GAHT resulted in procoagulant changes, which likely contributes to the observed increase in VTE risk. |
| Pyra et al (2020)15 | N = 4402 | Retrospective observational | 0.8% of transgender individuals receiving estrogen had a thrombotic event and 2.1% of transgender individuals receiving testosterone developed HTN. Among transgender individuals receiving estrogen, there was no association between thrombosis and GAHT as assessed by blood concentrations. | The AUthors found no association between GAHT and HTN or between GAHT and VTE. More research is needed to examine the effects of transgender individuals receiving estrogen. |
| Getahun et al (2018)6 | N = 102 417 | Retrospective observational | Transgender individuals receiving oral estrogen had a higher incidence of VTE, with 2- and 8-year risk differences of 4.1 (95% CI, 1.6-6.7) and 16.7 (CI, 6.4-27.5) per 1000 persons relative to cisgender men and cisgender women | Higher incidence of VTE and ischemic stroke were observed among transgender individuals receiving oral estrogen. |
| Arnold et al (2016)29 | N = 676 transgender individuals receiving estrogen | Retrospective observational | Transgender individuals receiving oral estradiol followed for 1.9 years. Only 1 individual, or 0.15% of the population, sustained a VTE, for an incidence of 7.8 events per 10 000 person-years. | There was a low incidence of VTE in this population of transgender individuals receiving oral estrogen. |
| Seal et al (2012)71 | N = 320 | Retrospective observational | Thromboembolism occurred in 1.2% of individuals, more frequently in those treated with CEE than in those treated with either estrogen valerate or ethinyl estradiol (4.4% vs. 0.6% vs. 0.7%, P = .026) | CEE is associated with a higher incidence of thromboembolism than treatment with other estrogen types. |
| Wierckx et al (2012)3 | N = 100 | Cross- sectional study | After being on hormone treatment for an average of 11.3 years, 6% of transgender individuals receiving estrogen experienced a thromboembolic event, and another 6% experienced other cardiovascular problems. | A number of transgender individuals receiving estrogen experience complications from GAHT, such as thromboembolic or other cardiovascular events, during hormone treatment, possibly related to older age, estrogen application, and lifestyle factors. |
| Ott et al (2010)30 | N = 251 | Retrospective observational | Activated protein C resistance was detected in 18/251 patients, and protein C deficiency was detected in 1 patient. None of the patients developed VTE GAHT. | VTE in GAHT is rare. General screening for thrombophilic defects in transgender individuals is not recommended. GAHT is feasible in individuals with APC resistance. |
| van Kesteren et al (1997)72 | N = 1109 | Retrospective observational | In both the transgender individuals receiving estrogen and transgender individuals receiving testosterone, total mortality was not higher than in the general population; the observed mortality could not be related to hormone treatment. | VTE was the major complication in transgender individuals treated with oral estrogens and antiandrogens, but fewer cases were observed since the introduction of transdermal estradiol in those over 40 years of age. |
| Study . | Patient demographics . | Study type . | Results . | Interpretation . |
|---|---|---|---|---|
| Manchkanti et al (2023)25 | N = 12 369 transgender individuals | Retrospective observational | The transgender individuals receiving estrogen had a lower incidence of cerebral infarcts (0.21% vs. 0.42%, P = .0003) and a moderately decreased incidence of MI (0.14% vs 0.22%, P = .062) compared to cisgender women. | The study observed decreases in rates of thrombotic events, acute MI, and cerebral infarction in transgender individuals receiving estrogen compared to cisgender women. |
| Mullins et al (2021)48 | N = 611 | Retrospective observational | Among 611 participants, 28.8% were transgender individuals receiving estrogen and 68.1% were transgender individuals receiving testosterone. The median age was 17 years at GAHT initiation. 5 individuals were treated with anticoagulation during GAHT: 2 with a previous thrombosis and 3 for prophylaxis. No participant developed thrombosis while on GAHT. | The findings suggest that, in youth, GAHT titrated within physiologic range does not carry a significant risk of thrombosis in the short-term. |
| Kozato et al (2021)41 | N = 407 | Retrospective observational | 407 transgender individuals receiving estrogen undergoing primary vaginoplasty. Of all cases, 1 patient presented with VTE from the cohort whose estrogen was suspended prior to surgery. No VTE events were noted among those who continued. | Perioperative VTE was not a significant risk in a large, homogenously treated cohort of transgender individuals, independent of whether estrogen was suspended prior to surgery. |
| Scheres et al (2021)5 | N = 198 | Prospective observational | Transgender individuals on estrogen GAHT developed increased factors IX and XI as well as a decrease in protein C. | In transgender individuals receiving estrogen, GAHT resulted in procoagulant changes, which likely contributes to the observed increase in VTE risk. |
| Pyra et al (2020)15 | N = 4402 | Retrospective observational | 0.8% of transgender individuals receiving estrogen had a thrombotic event and 2.1% of transgender individuals receiving testosterone developed HTN. Among transgender individuals receiving estrogen, there was no association between thrombosis and GAHT as assessed by blood concentrations. | The AUthors found no association between GAHT and HTN or between GAHT and VTE. More research is needed to examine the effects of transgender individuals receiving estrogen. |
| Getahun et al (2018)6 | N = 102 417 | Retrospective observational | Transgender individuals receiving oral estrogen had a higher incidence of VTE, with 2- and 8-year risk differences of 4.1 (95% CI, 1.6-6.7) and 16.7 (CI, 6.4-27.5) per 1000 persons relative to cisgender men and cisgender women | Higher incidence of VTE and ischemic stroke were observed among transgender individuals receiving oral estrogen. |
| Arnold et al (2016)29 | N = 676 transgender individuals receiving estrogen | Retrospective observational | Transgender individuals receiving oral estradiol followed for 1.9 years. Only 1 individual, or 0.15% of the population, sustained a VTE, for an incidence of 7.8 events per 10 000 person-years. | There was a low incidence of VTE in this population of transgender individuals receiving oral estrogen. |
| Seal et al (2012)71 | N = 320 | Retrospective observational | Thromboembolism occurred in 1.2% of individuals, more frequently in those treated with CEE than in those treated with either estrogen valerate or ethinyl estradiol (4.4% vs. 0.6% vs. 0.7%, P = .026) | CEE is associated with a higher incidence of thromboembolism than treatment with other estrogen types. |
| Wierckx et al (2012)3 | N = 100 | Cross- sectional study | After being on hormone treatment for an average of 11.3 years, 6% of transgender individuals receiving estrogen experienced a thromboembolic event, and another 6% experienced other cardiovascular problems. | A number of transgender individuals receiving estrogen experience complications from GAHT, such as thromboembolic or other cardiovascular events, during hormone treatment, possibly related to older age, estrogen application, and lifestyle factors. |
| Ott et al (2010)30 | N = 251 | Retrospective observational | Activated protein C resistance was detected in 18/251 patients, and protein C deficiency was detected in 1 patient. None of the patients developed VTE GAHT. | VTE in GAHT is rare. General screening for thrombophilic defects in transgender individuals is not recommended. GAHT is feasible in individuals with APC resistance. |
| van Kesteren et al (1997)72 | N = 1109 | Retrospective observational | In both the transgender individuals receiving estrogen and transgender individuals receiving testosterone, total mortality was not higher than in the general population; the observed mortality could not be related to hormone treatment. | VTE was the major complication in transgender individuals treated with oral estrogens and antiandrogens, but fewer cases were observed since the introduction of transdermal estradiol in those over 40 years of age. |
APC, argon plasma coagulation; CEE, conjugated equine estrogen; HTN, hypertension.