Earlier studies on the rat and the monkey had demonstrated that an injection of styrene maleic anhydride (SMA) in a solvent vehicle of dimethyl sulphoxide (DMSO) into the lumen of the vas deferens is toxicologically safe and has contraceptive action. Phase I clinical trial was therefore undertaken on 38 male volunteers giving varying doses of SMA, ranging between 5 mg and 140 mg, into each vas deferens. A dose of 70 mg is the predicted therapeutic dose based on animal data. That the compound is within the vas deferens lumen during the period of the safety assessment is inferred from the effect on the spermatozoa count in ejaculates which reach azoospermic levels in the higher dose ranges. The treatment is well tolerated with only minimal side effects in a few cases and no long-term adverse effects.
PIP: 38 men living in Delhi, India, volunteered to participate in a Phase I Clinical Trial of an injectable contraceptive (styrene maleic anhydride [SMA] in a solvent vehicle of dimethyl sulphoxide [DMSO] aimed to assess the safety of DMSO-SMA in humans. Physicians injected the DMSO-SMA mixture into the lumen of each vas deferens. All their wives had already undergone tubal occlusion. Low doses (5-20 mg) of SMA did not reduce the sperm count. Sperm counts did not change until the dose reached 40 mg, suggesting that the polymer SMA stayed in the vas deferens. Azoospermia did not occur until the SMA dose reached 70 mg, the predicted therapeutic dose based on animal data. Azoospermia did not take place until 34-80 days postinjection in most men. All the men reported normal sexual activity 10 days after the injection. 1 man receiving 40 mg SMA experienced some pain in the scrotal region and moderate scrotal enlargement. Antiinflammatory drugs resolved the situation. Another man received 140 mg and his scrotum increased to twice its regular size. He also experienced bilateral tenderness of the spermatic cord and inguinal canal. Antibiotics and antiinflammatory drugs resolved the swelling. He may have experienced a hypersensitive reaction to SMA. At least 2 years after treatment, all but 1 subject were health and had no complaints. 1 subject had committed suicide for reasons other than the DMSO-SMA injection. No longterm adverse effects occurred, indicting that DMSO-SMA is safe.