Thursday, August 05, 2004

One for the Boys

When it comes to male birth control, a method has to be able to prevent insemination. Insemination is the deposition of sperm in or near the vagina. There are two ways to disrupt insemination: mechanical or hormonal. The first one is relatively easy to accomplish: you cut the vasa, you use a condom. The hormonal route is more challenging. Why? Let's quickly compare the maturing of egg and sperm to give you an idea.

Each monthly cycle about 20 ovarian follicles are recruited to develop and mature. [Think of the follicle as a little individual egg nest inside the ovary.] By the end of the cycle--Day 14 in a 28-day cycle--only one follicle fully matures and one egg is expelled from the ovary. There are exceptions to this rule, but for the purpose of our discussion one ovary = once-a-month = one mature egg. The ovaries alternate in this function: one month the egg is released from the right ovary, the next from the left one. [So, even if one ovary is removed, fertility is retained.]


[Maturation starts top left, and progresses, clockwise, from top left (Follicules ovariques primaires = Primary ovarian follicle) to bottom middle (Ovocyte expulse = Ovulation); the yellow body (Corps jaune) is what's left of the follicle after the egg is released; the white body (corpus albicans) is what's left of the yellow body if no pregnancy occurs.]

Bottom line in a woman: from one primary/immature germ cell-->one egg; takes one month to mature; between two successive egg maturations the woman is not fertile (most of the month).

In contrast, a man produces and matures sperm, in the testicle, continuously. It takes about 64 days for sperm to mature. So, on any given day of the month a man has some immature, some developing, and some mature sperm. In other words, one testicle = continuously = millions of mature sperm. [To give you an idea of the numbers involved: an adult testicle produces approximately 1,000 sperms per second. So a single ejaculate may contain from 200 to 600 million sperm.]

Sperm development

Bottom line in a man: from one primary/immature germ cell-->four sperm; takes 64 days to mature; cells are in different stages of maturation, so man is fertile throughout the month.

In both women and men, hormones control the production of eggs/sperm. There are local hormones involved--estrogen, progesterone, and, in men, testosterone--and control hormones, called gonadotropins. All these hormones work in concert, and influence each other via feedback loops (e.g., high levels of one shut down production of another).

Finally, and briefly, hormonal birth control methods, like the Pill, work at the level of these hormones: they inhibit the gonadotropins. In women, all you have to do is prevent a once-a-month event, ovulation. You're not so much concerned with the development and maturation of the egg (which take place inside the ovary) as you are with blocking the release of a mature egg from the ovary. In contrast, in men your focus is on blocking the production/release of sperm, a continuous process.

So, now that we have the theory out of the way, let's look at the male birth control methods. Currently, the 3 widely-used methods are:

Coital techniques

Condom

Sterilization (Vasectomy)

Vasectomy is a surgical procedure in which the vasa deferentia (tubes involved in sperm transport) are cut and the passage of sperm is blocked. Because no sperm is present in the ejaculate, insemination is prevented.

The two techniques used are conventional, and no-scalpel (NSV); the procedure is a minor operation (when compared to female sterilization) lasting approximately 10-20 minutes. Usually only a local anesthetic is needed. A man is not sterile immediately after a vasectomy. It usually takes about 3 months (or 20 ejaculations) for all the mature sperm, stored in the vas beyond the blockage point, to be eliminated. An alternate method of birth control must be used during this period until sterility is verified. The 1st year failure rate is 0.15% with typical use, and 0.10% with perfect use. Vasectomy is the most effective method of male birth control currently available.

Reversal surgery (vasovasotomy or epididymovasostomy) is possible, but it involves more complex surgery than the initial procedure. The success rate of the reversal is low. Although it's possible to obtain a vas patency rate of 50% to 80%, the pregnancy rate is only about 30%.

The male methods under development can be divided into 7 groups:

Heat
Birth control pills
Injectables
Implants
Vaccines
Vasectomy
Plant compounds


Heat

Sperm can not form and mature at normal core body temperature. This is why the testicles are located outside the body, in the scrotal sac, where the temperature is several degrees cooler vs. the core body temperature.

Heat methods warm the testicles in order to inhibit sperm formation. The heat source can be either natural body heat (a special undergarment is used to elevate/keep the testicles very close to the body) or an external heat source (ultrasound waves, etc.). Further research is needed to establish the long-term effects of this method.

Birth control pills

a) Synthetic hormones
b) Nifedipine
c) Sugar pill

a) Synthetic hormones

If a man takes the hormone progestin, his body's secretion of gonadotropins is suppressed. This, in turn, inhibits sperm and testosterone (T) production in the testis; sperm counts are reduced to levels that are unlikely to cause pregnancy. Because the natural T production is suppressed, synthetic T needs to be added in order to maintain sexual drive. Birth control pills for men, containing a combination of a progestin and a synthetic T or just a progestin, have been studied.

A combination Pill (progestin and T), taken twice a day for 16 weeks, lowers the sperm counts to very low levels and appears to have few side effects. This pill has been tested in a small study.

Another progestin-only pill has been studied; the synthetic T is added usually in the form of an injection or patch. One drawback: it may take weeks to months to reach full effectiveness.

b) Nifedipine

Nifedipine is a widely used antihypertensive drug (a drug used to lower high blood pressure). A side effect of this medication is that it prevents the binding of the sperm to the egg. This could be useful for its future development as a male birth control pill.

c) Sugar pill

This method uses a sugar-based compound, administered in the form of a pill. The compound attaches to a sperm enzyme essential for egg recognition and penetration. Because this enzyme is blocked, sperm can not properly bind to the egg and fertilization is prevented.

Injectables (Shots)

a) Testosterones
b) Combination
c) GnRH Antagonists

a) Testosterones

If a man takes synthetic testosterone (T), his body's T production is inhibited. This, in turn, causes a dramatically suppressed sperm count. Because the synthetic T in the blood can not cross into the testicles, peripheral T levels remain high enough to preserve the man's libido. This represents an advantage, when compared to the progestin-only pill which suppress peripheral T levels. Three different types of synthetic T shots have been studied. [Interestingly, hormonal methods work better in Asian men than in Caucasian men; it's not yet clear why.]

b) Combination

A combination of a progestin and a synthetic testosterone (T) appears to be more effective in suppressing sperm formation than synthetic T alone. Also, by adding the progestin the dose of synthetic T can be lowered, thus reducing its potential side effects. Studies of a monthly progestin/T shot are currently underway.

c) GnRH Antagonists

A GnRH antagonist is a compound that blocks the production of gonadotropin-releasing hormone (GnRH). The lack of GnRH, in turn, causes the testicle to stop sperm and testosterone (T) production; the man's fertility is inhibited. Because the body's natural T synthesis is blocked, a synthetic T needs to be added. GnRH antagonists are administered as a subcutaneous injection (under the skin) and they've showed good effectiveness in small trials. The disadvantages of using this method: GnRH antagonists are difficult to produce, and maintaining their action with only one synthetic T has had mixed success.

Implants

One type of male hormonal implant consists of 2 rods: one rod has gonadotropin-releasing hormone (GnRH), and the other has the hormone nortestosterone (MENT). The hormones block the formation of new sperm, so the man is temporarily infertile.

Another type of male implant under study contains biodegradable testosterone pellets.

Vaccines

The methods in this group aim to use the body's own immune system to act as a contraceptive (via a birth control vaccine that could potentially "immunize" a man against being fertile). The vaccine could stimulate the body's immune system to create antibodies against something that is essential for the man's reproductive process. Potential targets that have been studied: sperm, epididymal proteins, and the gonadotropin follicle-stimulating hormone (FSH).

Anti-sperm vaccines contain one of two types of sperm antibodies (Abs): Abs against sperm metabolism, and Abs against sperm and egg interaction. Studies with sperm vaccines are underway.

In animal studies, immunization against FSH has resulted in significant decreases in sperm counts but inconsistent effects on fertility. The research on these vaccines is at the laboratory stage.

Vasectomy

a) Battery-powered capsules
b) Chemical injections
c) Silicone plugs
d) Reversible vasectomy

a) Battery-powered capsules

Small, battery-powered capsules can be implanted into each vas deferens, where they emit a low-level electrical current which immobilize passing sperm.

b) Chemical injections

Various chemical substances can be injected into each vas deferens, where they can produce enough scaring of the vas wall to block the passage of sperm. Obviously, the chemical must be able to scar the walls, and must also be nontoxic. This is a non-reversible method.

c) Silicone plugs

A plug device, consisting of very small silicone cylinders, can be inserted into each vas deferens and anchored with a tiny suture to the wall of the vas. The cylinder physically blocks the passage of sperm, and it has the advantage that it can be inserted and removed without using a scalpel. This device is also known as "the shug".

Another type of plug, consisting of a liquid form of polyurethane or silicone (MPU and MSR), can be injected into each vas deferens. Once injected, the material hardens (in about 20 minutes), and forms a plug that stops the passage of sperm. In addition, the plug also causes the vas to rupture which leads to scar tissue formation, further blocking sperm passage. These plugs are removed in an outpatient surgical procedure, usually requiring only one suture. A 98% sterility rate was noted in one study, and another study found the same rate after three years.

d) Reversible vasectomy

A substance called Styrene Maleic Anhydride (SMA) can be injected into the vas deferens, where it raises the acidity inside the vas. Because sperm can not live in an acidic environment, sperm passing through the vas are killed. This method is reversible because SAM can be flushed out of the vasa with an injected solvent. This procedure is also known as Reversible Inhibition of Sperm Under Guidance (RISUG).

Plant compounds

a) Tripterygium
b) Gossypol

a) Tripterygium

Tripterygium wilfordii is a plant used in traditional Chinese medicine. Daily doses of Tripterygium extract affect sperm motility and reduce sperm counts.

b) Gossypol

Gossypol, a plant compound derived from cotton-seed oil, has been tested as a birth control pill for men. It works by suppressing sperm production, but it also produces undesirable side effects: irreversible infertility in over 10% of men, and a low potassium level (hypokalemia). Gossypol has been studied since the 1970s and currently, due to its side-effects, some researchers do not support further studies; others are conducting ongoing studies in several countries.

As you can see from my limited review (I haven't even mentioned GnRh agonists and inhibin, or sulfasalazine, imidazoles, and pyrimethamine), researchers are working on a number of potential male birth control methods. Unfortunately, any wide-spread commercial use is years (probably decades) away. If you'd like to keep up-to-date with developments, malecontraceptives.org might be of use. [It appears to be a private site; good info, but I didn't have time to evaluate in-depth.]

Update: I replaced a picture (it was doing funny things to my blogroll) with a link.

1 Comments:

At 2:41 PM, Blogger PZ Myers said...

Say...you've got some good stuff on this here blog. Would you care to send me a link to one of your favorites so I can include it in the Tangled Bank this week?

(http://tangledbank.net/, if you don't know what I'm talking about.)

 

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