Associations of estrogen vs testosterone replacement therapy with complications after total joint arthroplasty: A systematic review

Table 1 Characteristics of included studies, mean ± SD

Ref.	Country	Study design	Total	Sample sizes (case/control)	Sex (men/women)		Age (years)		BMI (kg/m2)	Surgery	Study period (years)	Follow-up	Timing of use	Hormone type
					HRT	Non-HRT	HRT	Non-HRT
Ayala-Ortiz et al[21]	United States	Retrospective cohort study	34911	1711/33200	1359/352	12732/20468	NR	NR	NR	TKA	From 2015 to 2022	3 years	At least 3 months preoperatively	TRT
Prieto-Alhambra et al[22]	United Kingdom	Retrospective cohort study	10800	2700/8100 (only women)	2700	8100	64.5 ± 7.7	64.8 ± 8.4	28.4/28.5	THA and TKA	From 1986 to 2006	3.3 years	At least 6 and 12 months preoperatively/postoperatively	ERT
Hurbanek et al[23]	United States	Case-control study	318	108/210 (only women)	108	210	67	74	29/29	THA and TKA	From 1997 to 2002	NR	discontinued on the day of surgery or within 2 weeks preoperatively	ERT
Su et al[24]	United States	Retrospective cohort study	43997	2285/41712 (only men)	2285	41712	61.7 ± 9.4	66.2 ± 9.6	NR	TSA	From 2010 to 2020	2 years	Within 6 and 12 months preoperatively	TRT
Parmar et al[25]	United States	Retrospective cohort study	3812	1906/1906	1706/200	1706/200	68.66	68.73	NR	TSA	From 2010 to 2022	2 years	Within 90 days postoperatively	TRT
Corban et al[26]	United States	Retrospective cohort study	1443	481/962	481	962	60.6	60.5	NR	TSA	From 2017 to 2021	Up to a maximum of 3 years or until December 31, 2022	Within 12 months preoperatively	TRT
White et al[27]	United States	Retrospective cohort study	2738	1369/1369	668/701	652/717	68.3 ± 10.3	68.2 ± 10.4	31.2 ± 7.1/31.15 ± 6.7	TSA	Surgery before 2020	5 years	within 1 year preoperatively	TRT
Omurzakov et al[28]	United States	Retrospective cohort study	291517	6911/284606	2877/4034	102203/182403	67 ± 9.8	66 ± 10.7	NR	TKA	Surgery before 2020	5 years	within 1 year preoperatively	TRT
Ni et al[29], THA	United States	Retrospective cohort study	2888	1444/1444	1330/114	1330/114	61	61	NR	THA	From 2005 to 2025	3 months	within 3 months postoperatively	TRT
Ni et al[29], TKA	United States	Retrospective cohort study	3990	1995/1995	1853/142	1853/142	64	64	NR	TKA	From 2005 to 2025	3 months	within 3 months postoperatively	TRT
Mousavi et al[30]	United States	Retrospective cohort study	3558	1779/1779 (only women)	1779	1779	70.2 ± 8.3	70.4 ± 8.3	NR	TSA	From 2004 to 2024	NR	At least 1-5 years preoperatively	ERT
Jing et al[31]	United States	Retrospective cohort study	440	146/294 (only men)	146	294	NR	NR	NR	THA	NR	90 days	Within 3 months preoperatively	TRT
Coden et al[18]	United States	Retrospective cohort study	35299	3209/32090 (only men)	3209	32090	NR	NR	NR	TKA	NR	1.9 years	Within 1 year preoperatively	TRT
Collins et al[32], THA-TRT	United States	Retrospective cohort study	33423	6725/26698	6725	26698	61.7 ± 8.6	61.9 ± 8.5	NR	THA	From 2010 to 2021	2 years	Within 6 months preoperatively and 6 months postoperatively	TRT
Collins et al[32], TKA-TRT	United States	Retrospective cohort study	71292	14290/57002 (only men)	14290	57002	62.6 ± 8.0	62.6 ± 8.0	NR	TKA	From 2010 to 2021	2 years	Within 6 months preoperatively and 6 months postoperatively	TRT
Collins et al[32], THA-ERT	United States	Retrospective cohort study	31429	6302/25127 (only women)	6302	25127	66.6 ± 7.8	66.6 ± 7.7	NR	THA	From 2010 to 2021	2 years	Within 6 months preoperatively and 6 months postoperatively	ERT
Collins et al[32], TKA-ERT	United States	Retrospective cohort study	82477	16525/65952 (only women)	16525	65952	65.5 ± 8.0	62.6 ± 8.0	NR	TKA	From 2010 to 2021	2 years	Within 6 months preoperatively and 6 months postoperatively	ERT
Zhao et al[33], THA	United States	Retrospective cohort study	10275	3425/6850 (only women)	3425	6850	62	63	NR	THA	From 2015 to 2020	90 days	Within 90 days preoperatively and 90 days postoperatively	ERT
Zhao et al[33], TKA	United States	Retrospective cohort study	22227	7409/14818 (only women)	7409	14818	62	63	NR	TKA	From 2015 to 2020	90 days	Within 90 days preoperatively and 90 days postoperatively	ERT
McCormick et al[17]	United States	Retrospective cohort study	43296	3936/39360 (only women)	3936	39360	NR	NR	NR	THA	NR	NR	Within 12 months preoperatively	ERT

ERT: Estrogen replacement therapy; HRT: Hormone replacement therapy; THA: Total hip arthroplasty; TKA: Total knee arthroplasty; TRT: Testosterone replacement therapy; TSA: Total shoulder arthroplasty; NR: Not reported.

Table 2 Summary of the medical complications

Ref.	VTE	AKI	Pneumonia and sepsis	Cardiac event	Transfusion
ERT
Zhao et al[33]	DVT: OR = 0.52, 95%CI: 0.29-0.91, P = 0.028; PE: OR = 0.67, 95%CI: 0.34-1.32, P = 0.31	NR	NR	NR	NR
Collins et al[32]	THA: DVT (OR = 0.70,95%CI: 0.36-1.27), PE (OR = 1.40, 95%CI: 1.00-1.91). TKA: DVT (OR = 0.63, 95%CI: 0.44-0.88), PE (OR = 0.87, 95%CI: 0.72-1.05)	THA: OR = 0.96, 95%CI: 0.77–1.18; TKA: OR = 1.20, 95%CI: 0.99–1.27	NR	THA: OR = 1.15, 95%CI: 0.93-1.41; TKA: OR = 1.21, 95%CI: 1.05-1.38	THA: OR = 0.91, 95%CI: 0.92-1.01; TKA: OR = 0.85, 95%CI: 0.79-0.92
Hurbanek et al[23]	DVT: OR = 0.66, 95%CI: 0.35-1.18, P = 0.17	NR	NR	NR	NR
McCormick et al[17]	DVT: OR = 0.94, 95%CI: 0.70-1.25, P = 0.6601; PE: OR = 0.80, 95%CI: 0.47–1.36, P = 0.4102	OR = 1.02, 95%CI: 0.72-1.44, P = 0.922	NR	NR	NR
Mousavi et al[30]	DVT: RR = 1.909, 95%CI: 1.145-3.184, P = 0.012; PE: RR = 1.667, 95%CI: 0.933-2.979, P = 0.081	RR = 1.423, 95%CI: 0.866-2.34, P = 0.162	Sepsis: RR = 1.769, 95%CI: 0.899-3.481, P = 0.094	RR = 1.200, 95%CI: 0.520-2.77, P = 0.669	RR = 0.955, 95%CI: 0.527-1.729, P = 0.878
TRT
Ni et al[29]	PE: OR = 1.45, 95%CI: 1.04-2.02, P = 0.029; DVT: OR = 1.27, 95%CI: 0.98-1.65, P = 0.073	NR	NR	NR	NR
Omurzakov et al[28]	90 days: PE (OR = 1.4, 95%CI: 1.0-1.8, P = 0.041), DVT (OR = 1.2, 95%CI: 1.0-1.5, P = 0.127); 1 year: PE (OR = 1.3, 95%CI: 1.1–1.7, P = 0.015), DVT (OR = 1.4, 95%CI: 1.1-1.6, P < 0.001)	90 days: OR = 1.5, 95%CI: 1.2-1.8, P < 0.001; 1 year: OR = 1.6 95%CI: 1.4-1.8, P < 0.001	90 days: Pneumonia (OR = 1.8, 95%CI: 1.4-2.3, P < 0.001), sepsis (OR = 1.8, 95%CI: 1.3-2.4, P < 0.001); 1 year: Pneumonia (OR = 1.6, 95%CI: 1.3-1.8, P < 0.001), sepsis (OR = 1.7, 95%CI: 1.4-2.2, P < 0.001)	90 days: OR = 1.3, 95%CI: 1.0-1.8, P = 0.055; 1 year: OR = 1.3, 95%CI: 1.0-1.6, P = 0.018	NR
White et al[27]	90 days: VTE (OR = 1.42, 95%CI: 0.91-2.20, P = 0.121); 1 year: VTE (OR = 1.59, 95%CI: 1.15-2.21, P = 0.005)	90 days: OR = 1.37, 95%CI: 1.03-1.84, P = 0.033; 1 year: OR = 1.54, 95%CI: 1.25-1.91, P < 0.001	NR	90 days: OR = 1.48, 95%CI: 0.82-2.67, P = 0.185; 1 year: OR = 1.15, 95%CI: 0.75-1.76, P = 0.516	90 days: OR = 1.14, 95%CI: 0.69-1.89, P = 0.607; 1 year: OR = 1.38, 95%CI: 0.93-2.05, P = 0.110
Jing et al[31]	0.0% vs 0.7%, P = 1.00			0.0% vs 0.3% P = 1.00
Collins et al[32]	TKA: DVT (OR = 0.74, 95%CI: 0.51-1.06), PE (OR = 0.95, 95%CI: 0.75-1.19); THA: DVT (OR = 1.24, 95%CI: 0.77-1.98), PE (OR = 1.02, 95%CI: 0.68-1.50)	TKA: OR = 1.24, 95%CI: 1.10–1.40; THA: OR = 1.22, 95%CI: 1.01-1.47	NR	TKA: OR = 1.03, 95%CI: 0.91-1.16; THA: OR = 0.96, 95%CI: 0.80-1.15	TKA: OR = 0.74, 95%CI: 0.64–0.86; THA: OR = 0.90, 95%CI: 0.74-1.07

AKI: Acute kidney injury; CI: Confidence interval; DVT: Deep venous thrombosis; ERT: Estrogen replacement therapy; NR: Not reported; OR: Odds ratio; PE: Pulmonary embolism; RR: Risk ratio; THA: Total hip arthroplasty; TKA: Total knee arthroplasty; TRT: Testosterone replacement therapy; VTE: Venous thromboembolism.

Table 3 Summary of the implant-related complications

Ref.	Revision	PJI	PPF	Mechanical loosening
ERT
Mousavi et al[30]	90 days: OR = 1.250, 95%CI: 0.650-2.404, P = 0.503; 2 years: 4.2% vs 2.5%, P = 0.004; 4 years: 5.5% vs 3.4%, P = 0.003; 10 years: 7.0% vs 4.6%, P = 0.002	90 days: OR = 1.706, 95%CI: 0.941-3.093, P = 0.075; 2 years: 3.9% vs 2.9%, P = 0.116; 4 years: 5.1% vs 3.8%, P = 0.060; 10 years: 6.6% vs 4.6%, P = 0.007	90 days: OR 1.193, 95%CI: 0.938-1.517, P = 0.149; 2 years: 10.3% vs 8.2%, P = 0.028; 4 years: 10.7% vs 9.1%, P = 0.092; 10 years: 11.2% vs 9.6%, P = 0.124	90 days: OR = 1.000, 95%CI: 0.417-2.397, P = 1.000; 2 years: 1.2% vs 0.6%, P = 0.033; 4 years: 1.8% vs 0.9%, P = 0.020; 10 years: 2.2% vs 1.5%, P = 0.104
McCormick et al[17]	OR = 1.23, 95%CI: 1.05-1.45, P = 0.0105	OR = 0.87, 95%CI: 0.67-1.12, P = 0.2838	OR = 0.97, 95%CI: 0.70-1.35, P = 0.8692	OR = 1.39, 95%CI: 0.98-1.99, P = 0.0677
Collins et al[32]	TKA: OR = 1.31, 95%CI: 1.17-1.47; THA: OR = 1.11, 95%CI: 0.94-1.30	THA: OR = 1.01, 95%CI: 0.78-1.29	TKA: OR = 0.92, 95%CI: 0.67-1.27; THA: OR = 0.97, 95%CI: 0.72-1.29	TKA: OR = 1.12, 95%CI: 0.90-1.37; THA: OR = 1.45, 95%CI: 1.04-2.00
Prieto-Alhambra et al[22]	HRT ≥ 6 months: OR = 0.62, 95%CI: 0.41-0.94, P = 0.023; HRT ≥ 12 months: OR = 0.48, 95%CI: 0.29-0.78, P = 0.003; preoperative HRT: OR = 1.10, 95%CI: 0.69-1.77, P = 0.70	NR	NR	NR
TRT
White et al[27]	90 days: OR = 1.21, 95%CI: 0.70-2.09, P = 0.488; 1 year: OR = 1.60, 95%CI: 1.07-2.40, P = 0.021; 5 years: OR = 1.48, 95%CI: 1.10-1.99, P = 0.009	90 days: OR = 1.70, 95%CI: 1.03-2.81, P = 0.036; 1 year: OR = 2.05, 95%CI: 1.34-3.14, P < 0.001; 5 years: OR = 1.81, 95%CI: 1.31-2.49, P < 0.001	90 days: OR = 0.67, 95%CI: 0.38-1.21, P = 0.185; 1 year: OR = 0.65, 95%CI: 0.40-1.07, P = 0.086; 5 years: OR = 0.77, 95%CI: 0.52-1.14, P = 0.196	90 days: OR = 1.54, 95%CI: 0.86-2.76, P = 0.145; 1 year: OR = 1.32, 95%CI: 0.88-1.99, P = 0.179; 5 years: OR = 1.40, 95%CI: 1.04-1.88, P = 0.026
Omurzakov et al[28]	1 year: TKA OR = 1.6, 95%CI: 1.2-2.2, P = 0.002; 5 years: OR = 1.5, 95%CI: 1.2-1.8, P < 0.001	1 year: OR = 2.7, 95%CI: 2.0-3.7, P < 0.001; 5 years: OR = 2.3, 95%CI: 1.8-2.8, P < 0.001	1 year: OR = 2.8, 95%CI: 1.6-5.0, P < 0.001; 5 years: OR = 2.7, 95%CI: 1.9-4.0, P < 0.001	1 year: OR = 1.9, 95%CI: 1.3-2.9, P = 0.001
Collins et al[32]	TKA: OR = 1.27, 95%CI: 1.13-1.44; THA: OR = 1.46, 95%CI: 1.21-1.75	THA: OR = 1.67, 95%CI: 1.31-2.09	TKA: OR = 1.53, 95%CI: 1.00-2.29; THA: OR = 1.01, 95%CI: 0.64-1.56	TKA: OR = 1.34, 95%CI: 1.06-1.69; THA: OR = 0.84, 95%CI: 0.56-1.25
Su et al[24]	NR	Within 6 months prior: OR = 1.44, 95%CI: 1.03–2.01, P = 0.042; within 6-12 months prior: OR = 1.18, 95%CI: 0.83-1.68, P = 0.403	NR	NR
Parmar et al[25]	12.0% vs 11.0%, P = 0.335	1.4% vs 1.6%, P = 0.597	0.58% vs 1.05%, P = 0.105	2.5% vs 2.3%, P = 0.596
Ayala-Ortiz et al[21]	NR	NR	NR	NR
Corban et al[26]	1 year: 1.4% vs 0%, P < 0.001; 2 years:1.4% vs 0.2%, P = 0.003; 3 years: 1.4% vs 0.7%, P = 0.03	NR	NR	NR
Coden et al[18]	1 year: 1.30% vs 0.84%, P = 0.01; 2 years: 1.65% vs 1.02%, P < 0.001; 3 years: 1.71% vs 1.08%, P < 0.001; 4 years: 1.71% vs 1.10%, P < 0.001; 5 years: 1.75% vs 1.12%, P < 0.001	NR	NR	NR
Jing et al[31]	3.4% vs 0.3%, P = 0.017	NR	NR	NR

CI; Confidence interval; ERT: Estrogen replacement therapy; NR: Not reported; OR: Odds ratio; PJI: Periprosthetic joint infection; PPF: Periprosthetic fracture; THA: Total hip arthroplasty; TKA: Total knee arthroplasty; TRT: Testosterone replacement therapy.