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RISUG is an injectable compound that partially blocks the vasa deferentia (tubes that carry sperm), providing effective contraception for up to 10 years per dose. It is effective immediately, has few side effects, and has proven to be reversible in primate studies. This contraceptive has completed Phase I and II clinical trials in India (Guha 1997). Our research has convinced us that RISUG is the most promising of the potential male contraceptives.

How does it work?

RISUG is an acronym for Reversible Inhibition of Sperm Under Guidance, and is composed of styrene maleic anhydride (SMA) complexed with the solvent dimethylsulfoxide (DMSO) (Guha 1996). RISUG has two contraceptive effects: partial blockage of the vasa deferentia and disruption of the sperm that pass through it.

Sperm that are present in the ejaculate after RISUG has been administered have broken cell membranes (Chaudhury 2004). The membrane carries molecular keys that are needed to attach to an egg. It also contains packets of enzymes that are needed to dissolve the outer coating of an egg. Without those keys or enzymes, the sperm are functionally infertile. Researchers postulate that RISUG ruptures the membranes by stressing their ion exchange mechanisms (Lohiya 1998).

How is it delivered? How long does it take?

The first clinical trial of RISUG determined that an injection of 60 milligrams is the therapeutic dose (Guha 1993). The men who participated in that first trial have had RISUG implanted for 15 years and counting with no complications. The Phase II clinical trial volunteers have now been using RISUG for more than ten years. When RISUG was properly implanted, no pregnancies occurred during the 1-3 years of the study (Guha 1997), and informal follow ups with the volunteers have confirmed no pregnancies since. It's possible that smaller doses could provide shorter periods of contraception.

From India Today
Deeg Ram, pictured here with his wife Dayawati, was one of the first men to receive RISUG in 1990.

The compound can be injected using a no-scalpel procedure into the vasa deferentia, where it coats the walls within a matter of minutes. Practitioners of no-scalpel vasectomy should be able to adopt the technique relatively easily. Less skilled practitioners should be able to inject the compound after making a tiny incision that can be closed with one suture. Either technique would be an outpatient procedure completed within 15 minutes.

Once injected, the compound is anchored to the tiny folds on the inner surface of the vasa deferentia within 72 hours (Guha 2007). Dr. Guha recommends that his patients use condoms for 10 days following the procedure. This is by far the fastest acting of the potential male contraceptives; even a vasectomy can take up to 3 months to become fully effective.

What side effects are expected?

Some of the participants in the Phase II clinical trial reported slight swelling of the testes with no associated pain. The swelling resolved itself within 2 weeks of the injection with no treatment (Guha 1997). None of the RISUG trial participants have asked to leave the study because of uncomfortable side effects. By contrast, attrition rates during male hormonal contraceptive trials can be as high as 20% of participants.

RISUG does not cause the common side effects of a vasectomy: granulomas and an autoimmune response (Mishra 2003). A granuloma is an inflamed and sometimes painful nodule of tissue where sperm have leaked from the reproductive tract into the surrounding tissues. Men whose bodies form granulomas are having an auto-immune response to their own sperm. Once they exit the reproductive tract, the sperm are treated by the body as a foreign substance to be removed. Researchers hypothesize that RISUG does not cause these side effects because it does not fully block the vasa deferentia.

Another concern commonly associated with vas occlusion is decreased prostate health. But 8 years after receiving a RISUG injection, men from the Phase II clinical trials all had healthy prostates (Sharma 2001).

How long does it take to reverse?

Primate studies have shown that RISUG is readily reversible, but reversal has not yet been tested officially in humans. Researchers have even shown that multiple injections and reversals are effective in primates (Lohiya 2000). Since RISUG does not cause the type of auto-immune response associated with vasectomy, RISUG reversal should be much more reliably successful (Mishra 2003).

The compound can be removed by flushing the vasa deferentia with an injection. One study showed effective reversal using an injection of baking soda dissolved in water (Koul 1998). Another study reported a successful non-invasive reversal technique involving massage, vibration and low electrical current (Lohiya 1998).

Primate studies suggest that it would take several months for a complete reversal of RISUG’s contraceptive effects. Primates treated with RISUG for 1.5 years who underwent non-invasive reversal showed normal sperm production levels within 2-3 months (Lohiya 2005). Cellular-level changes seen in the vasa deferentia and testes during treatment are reversed within 3-5 months (Manivannan 1999, Lohiya 2005).

RISUG is moving forward in the US & India

In February 2010, a non-profit organization completed a technology transfer agreement for the use of RISUG in the United States.  They plan to make RISUG in the US and conduct preclinical tests to ensure its safety by the end of 2011.  If all goes well with the manufacturing and testing, RISUG could begin clinical trials among US men within the next 5 years.

RISUG has been in Phase III clinical trials in India since 2002. If the trial has positive results, RISUG can begin India’s regulatory approval process, the final step before selling the product. Phase III trials are designed to establish the safety and efficacy of a drug in a variety of body types. Over 100 men were participating in the Phase III RISUG trial when it was delayed for a number of reasons.

In October 2002, government officials aired concerns about RISUG in India's national press. Their concerns have since been resolved, but the controversy stalled the clinical trial for six months. The next delay was due to concerns about RISUG's initial toxicology tests. The Indian Council for Medical Research (ICMR) has reviewed the toxicology data three times and approved it each time. However, in February 2002, World Health Organization scientists stated that the 25-year-old toxicology studies did not meet more recent international standards. RISUG was submitted for a new round of tests at a US lab, and approved in July 2005. In March 2006, the trial was slated to resume at 4 centers around India. Then a manufacturing delay halted progress. The pharmaceutical company making RISUG was finally able to deliver a batch produced to the World Health Organization’s Good Manufacturing Practice (GMP) standards in March 2007.  The trial resumed in earnest in April 2007.  The trial’s data collection, analysis and publication process will take several years to complete.

In the meantime, another study of RISUG began in India. This study will follow up with the men who received RISUG in 2001 and 2002, providing information on the safety and effectiveness of RISUG after more than 5 years of use. Informal reports suggest that RISUG could be a safe, effective, and inexpensive contraceptive which works for many years in a single dose. Establishing RISUG’s long-term safety and effectiveness in formal clinical studies will make the case for its development and introduction that much stronger.


The Male Contraception Information Project maintains a complete list of the papers published by the group of RISUG researchers.

  • Chaudhury, K, AK Bhattacharyya and SK Guha (2004) “Studies on the membrane integrity of human sperm treated with a new injectable male contraceptive.” Human Reproduction 19(8): 1826-30.
  • Guha, SK, G Singh, S Anand, S Ansari, S Kumar and V Koul (1993) “Phase I clinical trial of an injectable contraceptive for the male.” Contraception 48(4): 367-75.
  • Guha, SK (1996) “Contraceptive for use by a male.” United States Patent #5,488,075.
  • Guha, SK, G Singh, S Anasari, S Kumar, A Srivastava and V Koul. (1997) “Phase II clinical trial of a vas deferens injectable contraceptive for the male.” Contraception 56(4): 245-50.
  • Guha, SK (2007) “Biophysical mechanism-mediated time-dependent effect on sperm of human and monkey vas implanted polyelectrolyte contraceptive.” Asian Journal of Andrology 9(2): 221-7.
  • Koul, V, A Srivastava and SK Guha (1998) "Reversibility with sodium bicarbonate of styrene maleic anhydride, an intravasal injectable contraceptive, in male rats." Contraception 58(4): 227-31.
  • Lohiya, NK, B Manivannan and PK Mishra (1998) “Ultrastructural changes in the spermatozoa of langur monkeys Presbytis entellus entellus after vas occlusion with styrene maleic anhydride.” Contraception 57(2): 125-32.
  • Lohiya, NK, B Manivannan and PK Mishra (2000) “Repeated vas occlusion and non-invasive reversal with styrene maleic anhydride for male contraception in langur monkeys.” International Journal of Andrology 23(1): 36-42.
  • Lohiya, NK, B Manivannan, PK Mishra, S Sriram, SS Bhande and S Panneerdoss (2005) “Preclinical evaluation for noninvasive reversal following long-term vas occlusion with styrene maleic anhydride in langur monkeys.” Contraception 71(3): 214-26.
  • Manivannan, B, PK Mishra and NK Lohiya (1999) “Ultrastructural changes in the vas deferens of langur monkeys Presbytis entellus entellus after vas occlusion with styrene maleic anhydride and after its reversal.” Contraception 59(2): 137-44.
  • Mishra, PK, B Manivannan, N Pathak, S Sriram, SS Bhande and S Panneerdoss (2003) “Status of spermatogenesis and sperm parameters in langur monkeys following long-term vas occlusion with styrene maleic anhydride.” Journal of Andrology 24(4): 501-9.
  • Sharma, U, K Chaudhury, NR Jagannathan and SK Guha (2001) “A proton NMR study of the effect of a new intravasal injectable male contraceptive RISUG on seminal plasma metabolites.” Reproduction 122(3): 431-6.


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