Research updates
2. New methods of contraception   p 4
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3. A contraceptive pill for men Link to the Medical Research Council web site
Hormonal contraception for men.
The principles behind a hormonal approach to male contraception have been known for over 50 years. They are outlined in Box 3.
Figure 5. The negative feedback loop.



Rising levels
Under normal circumstances, the testicles are stimulated to produce sperm by gonadotrophic hormones, secreted by the pituitary gland at the base of the brain.
The two hormones involved are luteinising hormone (LH) and follicle-stimulating hormone (FSH). The testicles respond to these hormones by generating large numbers of sperm (about 1000 a second) and testosterone, the male hormone. Testosterone has an inhibitory effect on the brain, and limits the secretion of LH and FSH through a classical negative feedback loop.
This self-regulating system can be disrupted by administering a testosterone derivative (sometimes reinforced with a progesterone) which severely suppresses the pituitary's secretion of gonadotrophin. The testicles, deprived of their normal gonadotrophic drive, show a dramatic decline in sperm production.
Box 3.
Side effects
The CDN has built on early studies sponsored by the World Health Organisation which showed that sperm production can be suppressed by testosterone. However, it was found that the doses of testosterone required to suppress sperm production completely, and hence inhibit fertility, are large and associated with side-effects such as acne, weight gain and unfavourable changes in lipid levels in blood.
Combined doses
The latest approaches from the CDN, led by Dr Richard Anderson, involve a combination of a progestagen with a low ‘replacement’ dose of testosterone. Progestagens are components of the female pill, where they have the effect of suppressing ovulation. In a similar way they can stop the production of sperm in men. As they also suppress the production of testosterone within the body, a small dose of testosterone needs to be given together with the progestagen, to replace it and return the testosterone levels to within normal physiological levels. Although progestagens are available in tablet form, so far there is no suitable testosterone preparation which is effective orally, and recent studies investigating the ‘male pill’ have involved a progestagen tablet together with testosterone implants or injections.
Trying an implant
The CDN has recently investigated the effects of desogestrel in combination with a testosterone implant on hormone levels and sperm production in male volunteers in Edinburgh and Shanghai. The implant consists of a small pellet, slightly bigger than a match head, which is inserted under the skin and slowly dissolves, releasing testosterone into the blood over a three-month period. The results show that sperm production is promptly suppressed in men who receive 300 mg or 150 mg desogesterol per day – the latter being the dose used in some contraceptive pills for women. The results demonstrated complete suppression of sperm production in all men in the 300 mg group (1 mg is 1 microgramme and is equivalent to a millionth of a gramme). On discontinuing desogestrel, sperm concentrations recovered to pre-treatment values within 16 weeks. The low dose of testosterone from the implant does not produce the undesirable side effects mentioned above. This is the first time that complete suppression of sperm production has been demonstrated in two different ethnic groups, whilst maintaining physiological levels of testosterone.
Clinical studies
Longer term studies, using larger numbers of volunteers, are now taking place in all centres. They will take at least five years and are required to confirm the safety and effectiveness of this promising new ‘male pill’.
Question 4

a) Explain what is meant by a negative feedback loop.

b) Why would injection of a testosterone derivative lead to a dramatic decline in sperm production?

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