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Nifedipine is a high blood pressure (hypertension) and migraine medication taken as a daily pill. The drug is manufactured by six major pharmaceutical companies, including Pfizer (Procardia), Aventis (Cardizem) and Bayer (Adalat). Nifedipine belongs to a class of drugs known as calcium channel blockers (CCBs). Verampamil hydrochloride is another CCB, and it may have similar contraceptive effects. Verampamil is manufactured by Searle (Calan), Knoll Pharmaceuticals (Isoptin) and Wyeth-Ayerst (Verelan).

Dr. Susan Benoff of New York University ’s North Shore Hospital was the first to recognize nifedipine’s contraceptive effect. Dr. Benoff was working at the hospital’s infertility clinic in 1992 when a couple sought fertility treatment after multiple rounds of failed in vitro (test tube) fertilization. Under a microscope, the husband’s sperm appeared normal, but tests showed that the sperm were missing an important binding chemical (mannose lectin), and that the sperm membranes contained higher than normal amounts of cholesterol (Benoff 1999 and 2001). When the husband switched to a different high blood pressure medication, the sperm membrane cholesterol level dropped and the couple was able to conceive within months (Hershlag 1995). Dr. Benoff reviewed her records and found that in quite a few previously mysterious cases of infertility, the men had been taking nifedipine.

How does it work?

CCBs are prescribed to those suffering from high blood pressure because they partially block the calcium channels in the cells of the heart and blood vessels. These calcium channels are tiny voltage gates across cell membranes that convey the electrical signals used by muscles to contract and relax. CCBs slow down the rate of calcium exchange, causing the circulatory system muscles to relax, and blood pressure levels to decrease.

From Lotrel
Calcium channels regulate the passage of calcium ions through cell membranes.

CCBs also partially block the calcium channels within the cell membranes of sperm. This affects sperm function rather than production. A man taking nifedipine produces a normal amount of sperm, and the sperm appear functional when viewed through a microscope. But in vitro tests show that these sperm cannot fertilize an egg.

Researchers in Dr. Benoff’s lab have observed that the sperm of men taking nifedipine have low levels of mannose lectin on the sperm cell membranes. Mannose lectin is a molecule which is critical for binding with an egg’s zona pellucida (outermost layer). Nifedipine treatment may physically prevent mannose lectins from moving to the surface of the cell membrane by stiffening the membrane with excess cholesterol (Goodwin 1997, Benoff 1998a).

Recent work in Dr. Benoff ’s lab has focused on determining the DNA sequence of sperms' calcium channels. They found that one end of a sperm’s calcium channel is completely different from the channels in heart muscle tissue. This means that it might be possible to tailor a drug that would affect only the sperm calcium channels. However, the researchers also found that there is probably more than one type of calcium channel in sperm membranes, which may need to be accounted for during drug design (Goodwin 1999).

How effective would it be?

There have been no clinical trials of CCBs as contraceptives, so there is no certain answer to this question. While the in vitro effectiveness of nifedipine has been proven (Kanwar 1993), other researchers have shown that patients at another infertility clinic who took various kinds of CCBs did not have to discontinue the drug before successful fertilization took place (Katsoff 1997).

Because CCBs do not alter sperm production, men attempting to take the drug off-label as do-it-yourself contraception cannot use sperm counts to assess its effectiveness. Tests of the sperm at a fertility clinic are the only way to measure nifedipine’s contraceptive effectiveness; a battery of these tests may cost between $300 and $600.

What side effects are expected?

Because there have been no clinical trials of nifedipine as a contraceptive, the effective contraceptive dose is unknown. Patients taking CCBs for hypertension experience a range of formulation- and dose-dependent side effects. There are a dozen different CCB formulations and the dose range is quite wide. This variability means that the reported incidence of side effects is also quite variable. The most common side effects, experienced by 2-12% of users, include swelling in the extremities (peripheral edema), lightheadedness, flushing and nausea. CCBs are not associated with any effects on hormones or libido.

Nifedipine has been on the market for 20 years. Its safety for sufferers of hypertension is well-established. However, if men with normal blood pressure take nifedipine as a contraceptive, the range and severity of side effects could be different. To date, nifedipine has not been tested in men with normal or low blood pressure (Opie 2000).

Lack of pharmaceutical industry interest

There are two industry-related road blocks to the development of nifedipine as a contraceptive. First, its major manufacturers may not want men to know about nifedipine’s contraceptive effects. Customers taking the drug as a hypertension or migraine prescription may not appreciate its contraceptive properties. The manufacturers could easily lose market share in future hypertension prescriptions if the controversy were made public. Second, the patents on the formulation of nifedipine have expired. Other drug companies have begun manufacturing generic nifedipine, undercutting the drug’s price. Because they no longer retain the exclusive right to manufacture nifedipine, large drug companies have little incentive to invest in developing it as a contraceptive. And Dr. Benoff has a patent on the use of several different CCBs as male contraceptives until 2016 (Benoff 1998b).

Due to the lack of industry interest, Dr. Benoff is pursuing other funding options. There now several other groups of researchers working from various angles toward a better understanding of sperm calcium channels and the processes leading to sperm-egg fusion. The work of these different groups may eventually reveal other approaches for drug development.


  • Benoff, S (1998a) “Voltage dependent calcium channels in mammalian spermatozoa.” Frontiers in Bioscience 3: D1220-40.
  • Benoff, S (1998b) “Male contraceptives” United States Patent # 5,854,254
  • Benoff, S (1999) “Method for assessing infertility by binding of mannose to sperm cells.” United States Patent # 5,994,086
  • Benoff, S (2001) “Method and kit for detecting fertility” United States Patent # 6,258,525
  • Goodwin, LO, NB Leeds, I Hurley, FS Mandel, RG Pergolissi and S Benoff (1997) “Isolation and characterization of the primary structure of testis-specific L-type calcium channel: implications for contraception.” Molecular Human Reproduction 3(3): 255-68.
  • Goodwin, LO, NB Leeds, D Guzowski, IR Hurley, RG Pergolizzi and S Benoff (1999) “Identification of structural elements of the testis-specific voltage dependent calcium channel that potentially regulate its biophysical properties.” Molecular Human Reproduction 5(4): 311–22.
  • Hershlag, A, GW Cooper and S Benoff (1995) “Pregnancy following discontinuation of a calcium channel blocker in the male partner.” Human Reproduction 10(3): 599-606.
  • Kanwar, U, RJ Anand and SN Sanyal (1993) “The effect of nifedipine, a calcium channel blocker, on human spermatozoal functions.” Contraception 48(5): 453-70.
  • Katsoff, D, and JH Check (1997) “A challenge to the concept that the use of calcium channel blockers causes reversible male infertility.” Human Reproduction 12(7): 1480-2.
  • Opie, LH, S Yusuf and W Kubler (2000) “Current status of safety and efficacy of calcium channel blockers in cardiovascular diseases: a critical analysis based on 100 studies.” Progress in Cardiovascular Diseases 43(2): 171-96.


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