Use of Anabolic Steroids in Patients Undergoing Total Knee Replacement: A Systematic Review

Total knee arthroplasty (TKA) is an effective surgical treatment for advanced osteoarthritis, but postoperative recovery is frequently limited by quadriceps weakness, muscle atrophy, and prolonged rehabilitation. Anabolic steroids, such as nandrolone decanoate and testosterone, have demonstrated potential benefits in enhancing muscle strength, functional mobility, and bone density. This systematic review, conducted according to PRISMA guidelines and registered with PROSPERO, evaluated the efficacy and safety of anabolic steroid interventions in patients undergoing TKA. Two randomized controlled trials were identified: one assessed postoperative nandrolone administration, and the other evaluated preoperative supraphysiological testosterone therapy. Both studies reported improvements in quadriceps strength, functional outcomes, and early recovery parameters, with favorable safety profiles and no major adverse events. Nandrolone was associated with higher Knee Society Scores and reduced muscle weakness over 12 months, while testosterone improved early functional independence and shortened rehabilitation needs. Although encouraging, the findings are limited by small sample sizes, variability in dosing regimens, and short follow-up durations. Larger, multi-center studies are warranted to confirm efficacy, optimize treatment protocols, and assess long-term safety. Anabolic steroids may represent a promising adjunct to rehabilitation strategies in selected TKA patients, particularly older adults at risk of poor recovery.

Keywords: Total knee arthroplasty, anabolic steroids, quadriceps strength, functional recovery, testosterone, nandrolone

Introduction

Total knee arthroplasty (TKA) is a highly effective procedure for treating severe osteoarthritis and improving patients’ quality of life by alleviating pain and restoring mobility. However, patients, particularly older adults, often face significant challenges during recovery, including muscle atrophy, reduced functional mobility, and prolonged rehabilitation times. Preoperative disuse atrophy and postoperative muscle weakness, especially in the quadriceps, have been linked to slower recovery and diminished outcomes. After TKR, quadriceps weakness is most commonly seen especially in elderly patients, even following extensive rehabilitation^1,2. This leads to functional limitation despite successfully done TKR. Exploring therapeutic strategies to enhance recovery and functional performance after TKA is essential.

Androgenic anabolic steroids are a class of compounds chemically related to testosterone, the male sex hormone. They are characterized by their effects of promoting muscle growth (anabolic properties)³ and inducing masculinization (androgenic properties). Anabolic steroids, such as nandrolone decanoate and testosterone, have well-documented anabolic effects on muscle mass and strength. Evidence from studies on athlete populations indicates that anabolic androgen use can lead to significant increases in lean body mass and strength, with gains reaching up to 20%⁴. Historically associated with athletic performance enhancement, their potential in clinical rehabilitation contexts, including TKA recovery, has gained interest⁴. This review evaluates the impact of anabolic steroid interventions on muscle recovery, functional outcomes, bone density, and hospital stay duration following TKA.

Methods

The study was registered on the PROSPERO International Prospective Register of systematic reviews. Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria were used to perform the study⁵. From conception of database until November 2024, two reviewers (VP and DK) searched the four Internet databases (PubMed, Embase, Scopus, and The Cochrane Library). No restrictions were applied based on language or publication status. The key terms used for searching the databases were: “anabolic steroids,” “androgenic anabolic steroids,” “Total knee arthroplasty,” “TKA,” “Total knee replacement,” “TKR.” We also manually scanned the bibliographies of the included articles for other relevant studies. For further relevant research, references from published original articles and earlier studies were searched (Table 1) and depicted in the PRISMA chart in figure-1.

Table 1: Search Methodology

DATABASE	DATE: 25/11/2024	TOTAL RESULTS = 23
PUBMED	(“anabolic androgenic steroids”[MeSH Terms] OR (“anabolic”[All Fields] AND “androgenic”[All Fields] AND “steroids”[All Fields]) OR “anabolic androgenic steroids”[All Fields] OR (“anabolic”[All Fields] AND “steroids”[All Fields]) OR “anabolic steroids”[All Fields]) AND (“arthroplasty, replacement, knee”[MeSH Terms] OR (“arthroplasty”[All Fields] AND “replacement”[All Fields] AND “knee”[All Fields]) OR “knee replacement arthroplasty”[All Fields] OR (“total”[All Fields] AND “knee”[All Fields] AND “replacement”[All Fields]) OR “total knee replacement”[All Fields])	4
SCOPUS	( TITLE-ABS-KEY ( anabolic AND steroids ) OR TITLE-ABS-KEY ( androgenic AND anabolic AND steroids ) AND TITLE-ABS-KEY ( total AND knee AND replacement ) OR TITLE-ABS-KEY ( tkr ) )	5
EMBASE	(anabolic AND steroids OR androgenic) AND steroids AND total AND knee AND replacement	6
COCHRANE	(anabolic steroids):ti,ab,kw OR (androgenic anabolic steroids):ti,ab,kw AND (total knee arthroplasty):ti,ab,kw AND (TKR):ti,ab,kw	8

Study Characteristics

Table 2: Details of the studies included

Study	Study design	No. of participants	Intervention	Outcome
Hohmann et al	Prospective Randomised double blind trial	10	50mg nandrolone decanoate I.M twice weekly for 6 months	Knee society score⁸, Functional test- sit to stand, timed walk, Bone mineral density, Isokinetic strength testing
Amory et al	Prospective Randomised placebo controlled double blind trial	25	600mg testosterone enanthate intra muscularly once weekly for 4 weeks preoperatively	Length of hospitalization, Functional recovery- standing, walking and stair climbing

Results

Muscle Strength and Functional Outcomes

Bone Mineral Density

Hospital Stay and Rehabilitation

Safety and Side Effects

A key strength of the reviewed studies is the favourable safety profile of anabolic steroids in the studied populations. Both nandrolone and testosterone were well-tolerated, with no major adverse events reported. Minor side effects, such as hematocrit fluctuations, were observed but deemed clinically insignificant. However, it is important to recognize that long-term use of anabolic steroids, particularly at supraphysiological doses, has been associated with potential endocrine, cardiovascular, and hepatic risks^9,4. Therefore, careful monitoring of patients receiving anabolic steroids is necessary to ensure safety, especially in older adults with preexisting comorbidities.

Discussion

Implications of Findings

The findings from the reviewed studies underscore the promising role of anabolic steroids, such as nandrolone and testosterone, in enhancing recovery after total knee arthroplasty (TKA). A consistent benefit observed in both studies was the improvement in muscle strength, particularly in the quadriceps, which is crucial for post-TKA functional recovery. Quadriceps weakness has been widely documented as a major contributor to prolonged rehabilitation times and reduced functional outcomes following TKA, particularly in older adults². By counteracting muscle atrophy and promoting strength recovery, anabolic steroids address a critical challenge in postoperative care.

The study by Hohmann et al. demonstrated that patients receiving nandrolone decanoate exhibited significant improvements in quadriceps strength at multiple time intervals postoperatively (3 months, 6 months, and 12 months). This result is clinically significant because muscle strength recovery is directly linked to improved functional outcomes, such as walking ability, sit-to-stand performance, and stair-climbing. The Knee Society Score (KSS), a validated measure of knee function and pain, was also notably higher in the nandrolone group, reinforcing the potential benefits of anabolic steroids in improving overall knee performance.

Similarly, the findings of Amory et al. highlight the benefits of preoperative testosterone administration which exhibited enhanced early recovery, particularly in functional independence measures (FIM) such as standing, walking, and stair climbing. This early functional recovery can significantly reduce rehabilitation times and improve patient independence. While the improvements in walking and stair-climbing were not always statistically significant, trends in favour of anabolic steroid use were consistently observed, suggesting a meaningful clinical benefit even in small sample sizes.

An additional benefit observed in the studies was the potential role of anabolic steroids in preserving bone mineral density (BMD)^10,11. Hohmann et al. reported a smaller decrease in BMD in patients receiving nandrolone compared to controls, although the difference was not statistically significant. Maintenance of bone density is an important factor in long-term recovery, as reduced BMD can increase the risk of periprosthetic fractures, particularly in older adults with osteoporosis¹². Further studies are needed to determine the magnitude and consistency of this benefit.

Mechanisms of Action

The beneficial effects of anabolic steroids can be attributed to their physiological mechanisms. These compounds exert their anabolic effects by enhancing protein synthesis, leading to increased muscle mass and strength. In the postoperative period, anabolic steroids may accelerate muscle recovery by promoting muscle protein anabolism¹³, counteracting catabolic processes associated with surgical stress and immobilization.

Furthermore, testosterone, in particular, has additional systemic benefits, such as improving hematopoiesis¹⁴ and increasing red blood cell mass, which may contribute to enhanced oxygen delivery and improved endurance during rehabilitation. This effect may also reduce the need for blood transfusions, which are often required after major surgeries like TKA, particularly in older adults. The ability of testosterone to address multiple physiological aspects makes it a potentially valuable adjunct to traditional rehabilitation strategies.

Limitations

Despite the encouraging results, several limitations must be acknowledged. Both studies included in this review had relatively small sample sizes, which limit the generalizability of their findings. For instance, Hohmann et al. included only 10 patients, while Amory et al. had a sample size of 25. Larger, multi-center trials are necessary to confirm these findings and establish more robust evidence.

Additionally, there was variability in the dosing regimens and timing of administration across the studies. Hohmann et al. administered nandrolone bi-weekly for 6 months postoperatively, while Amory et al. used a supraphysiological dose of testosterone preoperatively for 4 weeks. This heterogeneity makes it challenging to determine the optimal dosing regimen and treatment duration for maximizing benefits. Standardized protocols are needed to facilitate comparisons across studies and guide clinical practice.

The short duration of follow-up in both studies is another limitation. While improvements in muscle strength and functional outcomes were observed in the short term, the long-term effects of anabolic steroids on functional recovery, bone health, and overall quality of life remain unclear. Long-term follow-up is crucial for evaluating the sustainability of benefits and identifying any delayed adverse effects.

Future Directions

To better understand the role of anabolic steroids in TKA recovery, future research should:

Conclusion

Anabolic steroids, such as nandrolone and testosterone, show promise in enhancing postoperative recovery following TKA by improving muscle strength and functional mobility. By improving muscle strength, functional outcomes, and possibly bone density, anabolic steroids hold significant promise for enhancing recovery, particularly in older adults at risk of prolonged rehabilitation. However, further large-scale, high-quality studies are needed to confirm these findings, establish clear treatment guidelines, and ensure the long-term safety of anabolic steroid use in clinical practice.

Use of Anabolic Steroids in Patients Undergoing Total Knee Replacement: A Systematic Review