The male contraceptive drug being developed by Dr. Joseph Hall is not based on a drug with other medical uses. Dr. Hall is designing a drug that would make sperm functionally infertile, but the drug would not affect sperm's ability to swim nor the rate of spermatogenesis (production of new sperm). Tests of Dr. Hall’s preliminary drug design show that it prevents sperm from recognizing and binding to an egg, resulting in 92% effective contraception in rats.
How would it work?
To disrupt fertilization, the drug uses the specialized chemical lock and key systems found on sperm and egg surfaces. Enzymes are chemical locks that only fit the properly shaped key. Enzymes recognize chemical keys that have exactly the right shape in all three dimensions; some enzymes are so specific that they have only one chemical key while others may have multiple chemical keys.
Several enzymes embedded in the cell membrane (the outer surface) of a sperm head recognize chemicals found in an egg’s zona pellucida (ZP, the outermost coating). The ZP chemicals are glycoproteins, or molecules made of a protein joined with a sugar. When the sperm enzymes encounter the ZP glycoprotein, they bind to them (Hall 1997). The enzymes then cut the egg's glycoprotein, essentially dissolving the outer coating of the egg and allowing the sperm to work its way through.
The drug Dr. Hall is developing mimics the ZP glycoprotein and binds to the sperm’s enzyme (type B N-acetyl-β-D-hexosaminidase or HEX-B) before the sperm even leave the man’s body (Hall 1996). A man taking this drug would produce sperm in the normal quantity, and the sperm would appear normal when viewed under a microscope, but they would not bind to an egg. The drug would not interfere with a man’s hormones or libido.
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| Dr. Joseph Hall, challenged by his wife, mother of their six children, to create a pill for men. |
How effective would it be?
Dr. Hall ’s team of researchers has tested the ZP glycoprotein mimic in vitro (in test tubes) with rat, bull and ram semen. They found that after treatment, 98% of each of these animals’ sperm did not bind to the eggs of their respective species. When they tested it in vivo, dissolving the protein into the drinking water of rats, they found that it was only about 90% effective (Lucas1997). Treated rats suffered no visible side effects, nor any changes in hormone levels. One week after stopping the treatment, the rats' fertility was fully restored.
The researchers have eliminated one possible mechanism for the lower observed in vivo effectiveness; they have confirmed that the drug stays bound to the surface of rat sperm even after 7 hours in the female reproductive tract (Tubbs 2002). The researchers now suspect that there are enzymes other than HEX-B involved in binding to an egg. Using three-dimensional computer models, they are tailoring the shape of the drug to act as a key for all these enzymes (Hall 2005). They may not be able to make just one molecule fit multiple enzyme locks, so their final product may be a cocktail of several different drugs.
This drug is in the preliminary stages of design and development. It has yet to be tested for mutagenicity, toxicity or carcinogenicity. Until these tests are complete, the drug cannot gain approval for a trial in humans. It will likely be many years before it becomes an FDA-approved pill or patch.
References
- Hall, JC, FM Perez, JG Kochins, CA Pettersen, Y Li, CE Tubbs and MD LaMarche (1996) “Quantification and localization of N-acetyl-β-D-hexosaminidase in the adult rat testis and epididymis.” Biology of Reproduction 54: 914-29.
- Hall, JC (1997) “X-ray crystallographic and affinity labeling analysis of the structure of rat epididymal N-acetyl-β-D-hexosaminidase: Insight into the Catalytic Mechanism.” National Science Foundation award abstract #9804595.
- Hall, JC (2005) Email to Kirsten Thompson, Male Contraceptive Coalition. 14 February.
- Lucas, T (1996) “New synthetic compound could lead to male contraceptive pill.” NC State News Services, 21 February.
- Tubbs, CE, JC Hall, RO Scott, VP Clark, TL Hermon and C Bazemore-Walker (2002) “Binding of protein D/E to the surface of rat epididymal sperm before ejaculation and after deposition in the female reproductive tract.” Journal of Andrology 23(4): 512-21.
