Table 2.

Synopsis of animal studies.

Ref	Sample Size/Model	Gender	OA Modelling	Assessment	Follow-Up	Major Findings
Bao et al. [20]	n = 108/rabbit n = 54: DHEA n = 54: control	M	ACLT	Histologic evaluation Gene expression	6, 9, and 12 weeks	Cysteine proteinases/cystatin C system and urokinase plasminogen activator/plasminogen activator inhibitor-1 system contribute to OA development DHEA suppresses both systems up to 9 weeks, but not up to 12 weeks DHEA exerts an anti-OA effect on the early stages of the disease
Huang et al. [21]	n = 30/rabbit n = 10: sham operation n = 15: DHEA n = 15: placebo	M	ACLT	Histologic evaluation	9 and 16 weeks	DHEA treatment delayed cartilage degeneration for up to 9 weeks DHEA treatment delayed cartilage degeneration for up to 16 weeks, but only in the lateral knee compartment DHEA can exert an anti-OA effect both on the early and middle stages of the disease
W. Li et al. [22]	n = 42/rabbit n = 12: sacrificed while the OA model establishment n = 6: DHEA n = 6: DHEA + letrozole n = 6: DHEA + fulvestrant n = 6: DHEA + letrozole + fulvestrant n = 6: DMSO (control)	N/A	ACLT	Histologic evaluation Gene expression	9 and 12 weeks	The effects of DHEA are attenuated by the aromatase inhibitor letrozole and the estrogen receptor inhibitor fulvestrant The effects of DHEA may be mediated by its conversion to estradiol
Jo et al. [23]	n = 22/rabbit n = 22: DHEA (right knee) n = 22: control (left knee)	N/A	ACLT	Histologic evaluation Gene expression	9 weeks	DHEA treatment delayed cartilage degeneration for up to 9 weeks: IL-1β MMP-1 MMP-3 TIMP-1
Wu et al. [24]	n = 40/rabbit n = 20: DHEA n = 20: control	N/A	ACLT	Histologic evaluation Gene expression	11 weeks	DHEA treatment delayed cartilage degeneration for up to 11 weeks: IL-1β (in the synovium, but not in the cartilage) MMP-3 TIMP-1
Huang et al. [25]	n = 10/rabbit n = 10: DHEA (one knee) n = 10: control (another knee)	M	ACLT	Gene expression	9 weeks	Aggrecanases TIMP-3
Ma et al. [17]	n = 139/mouse	M (intact and ORX) F (intact and OVX)	MMD	Histologic evaluation	8 weeks	Male mice had more severe OA than female mice Intact male mice had more severe OA than ORX mice, but the addition of DHT to ORX male mice re-established OA severity Intact female mice had more severe OA than OVX females, i.e., ovarian hormones decreased the severity of OA in female mice

ACLT—anterior cruciate ligament transection; MMP—matrix metalloproteinase; TIMP—tissue inhibitor of matrix metalloproteinase; MMD—medial meniscus destabilization; ORX—orchiectomized; OVX—ovariectomized.