Anti-androgenic drugs are treatments for androgen-related disorders such as benign prostatic hyperplasia, acne, hirsutism, and androgenic alopecia. Germacrone (1), a sesquiterpene isolated from hexane extracts of Curcuma aeruginosa Roxb. rhizome, is an androgen inhibitor of steroid 5-alpha reductase in- vitro. Here, we used the similarity of germacrone's ,t,B-unsaturated carbonyl to testosterone's α,β-unsaturated carbonyl to find germacrene analogs obtained from this plant and by semi-synthesis that might be more potent steroid 5-alpha reductase inhibitors. 8-Hydroxy germacrene B (4) was -13-fold more potent than its parent, I and the most potent (ICso, 0.15 ± 0.022 mM) among 9 compounds tested. The conformation of its cyclodecadiene ring and the α,β-unsaturated ketone/hydroxy in the germacrene molecule might be crucial role for its anti-androgen activity. Moreover, I and 4 showed mild cytotoxic effect on prostate cancer cells. Neither compound was cytotoxic towards human dermal papilla cells at 100 μg/mL. We show that this SAR strategy created promising anti-androgenics for androgen dependent disorders and may create further analogues with further improvements in selectivity and clinical efficacy.