Chemistry of Birth Control Pills Anil Saxena School of Chemistry and Molecular Sciences, University of Sussex, Brighton EN1 9QJ. U.K. The commercial production of a birth control pill is perhaps the most significant achievement in the ceaseless efforts of scientists engaged in preparing chemicals acting as antifertility agents. The convenience involved in the usage of these contraceptives has made them popular in human society. However, a few only are aware of its constitution and mode of action. Further work related to the manufacturing of "the pill" as i t is usually termed, is aimed in cutting down the production costs, minimizing their side effects, and increasing their potentiality. The pill usuallv contains the svnthetic sex hormones estrogen ifemale sex hormone) and progesterone (pregnancy hormone). Both of these hormones are steroids, a class of compounds whose skeleton is composed of cyclopentanoperhvdroohenanthrene with different suhstituents. ~ t ( w i ( lart' i we11 known to pliiy intriguing roles in the various metabolic orucesses. Steroids exert their artion hs first binding to specific protein "receptors" present in certain cells, and the various suhstituents on the steroid nucleus play a critical role in determining this interaction. However, it is amazing to note that though their basic chemical structures are remarkably similar, their biological activities are markedly different. The isolation of steroids from olants has been a landmark in the development of an oral contraceptive since animal sources seemed to he impracticable raw materials for extracting progesterone. I t had been reported previously that these hormones were detected in nature in very low concentration from tons of source materials like animal brains, spinal cords. cow's ovaries. urine of . meenant mares. etc. and hence .. were wry exprniiw:. It was Russrll Marker who iuccr~sfuIIy converted the olant steroid "dioiseenin" (extracted from the roots of various plants of family ~ k a c e a eto j progesterone in the laboratow. l'incus in 1'9:lO ohserved that injections of progesterone to female anin~alsinhibit ovulation, and Raohael Kurzrok in 1937 suggested that such inhibition of-ovulation would prohahlv be a safe method for contraception. Later John Rock. at Haward University and an cmrri111sl)rof(ss +
for contraception when taken orally. This proved to he a good oral contraceotive. hut its initial samoles were contaminated by ~ e s t r a n o ian , estrogen from whichit was synthesized. The purified samples, however, showed ponr results and so the use uf the mixture was recommended. It was this mlxiure that was used as the first hirth control pill. Other oral contraceptives were prepared by inserting different suhstituents at various positions on the steroid nucleus. A combination of the two (Norethynodrel plus Mestranol) proved effective as a once-a-month contraceptive. Since contraception is interference with the conception process, it is essential to know how conceotion occurs. A woman's normal estrogen and progesterone ievels undergo a cyclic rise and fall every month. When the levels reach their lowest points, the hypothalamus (a control center in the brain) sends out release factors that initiate the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) hy the anterior pituitary, thus initiating the ovulation process. The FSH and LH causes one of the Graafian follicles in the ovary to mature and rupture expelling an ovum (egg cell) into the fallopian tuhe. The liberation of an egg cell is called ovulation. The egg then passes through the fallopian tuhe bound for the uterus. This requires not more than 24 hours, and it is the only time when fertilization can occur. If the egg meets a sperm cell durine this oeriod. it is fertilized and then passes on into the uterus where it attaches itself on the endometrium (the uterus linine). Once the eee is firmlv implanted, conception has occurred.if the egg doesnot meet a sperm cell, i t passes unfertilized into the uterus where i t hriaks down and is sloughed out during menstruation. The ovulation process then repeats itself. A worn& under the influence of a pill is maintaining a state of ~seudo~reenancv. Because of her artificiallv elevated hormone l&els her brain assumes, in effect, that shk is already pregnant. The hypothalmic and pituitary hormones are not released and ovulation is inhibited. Since ovulation does not occur, there is no egg cell to he fertilized at any time, hence, there can he no conception. The pills also increase the viscosity of the cervical mucus, thus impeding sperm transport, and they alter the nature of the endometrium making it less receptive to attachment by a fertilized egg. The total effect of the hormones in these tablets is not ~ o & ~ l e t understood, el~ hut it is clear that they affect the blood and various metabolic processes along with their contraceptive action. Although the use of these pills approaches 100%effectiveness, unfortunately they also have side effects. Some effects are even desirable. Some are fairly minor-temporary nausea, weight gain, mild headache. skin ~rohlems.etc.. hut others are causes for true concern (blood clotting, hypeitension, gall bladder diseases, etc.). The most serious risk to women taking these pills is that of thromboemholism, the formation of blood clots. The risk increases with age especially in a women past 40, hut the factor that appears to he more critical is whether or not the woman smokes. There seems to he a strong svnergistic effect when a woman who takes hirth control pins also smokes. The investigation of other methods of contraception continues. These include the production of a reversihle lifetime contraceptive and an oral male pill. The reversible lifetime contraceptive is intended to he a rhernical that,once taken by a sexually mature woman, will hr nciivt. throughout her lifetime hut ran he deactivated when she desires motherhood. In ~~
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Number 12 December 1984
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the field of male physiology, numerous compounds have been found that interfere with sperm production, but they have severe side effects. Still, an acceptable contraceptive for men might well become a practical reality one day. There is no question about who caused the population explosion. I t was the scientist with his unquenched curiosities, so greatly extending life expectancy and reducing infant mortality. The scientists have come up with some wonderful means of death control. Let us hope that he can do as well with birth control.
Acknowledgment
I am thankful to C. Eaborn for encouragement. Literature Clted (1) Appleweig, N.,"Skroid Drugs:' MeCrsw Hill Bwk Ca., New York, 1962. (2) Benneth, J. P., "Chemid Contraception: Columbia Univereity Press, New York, 1974. (3) Beet, W. R.. "Hormone ChemisUy," V0l. 2. I1 ed, John WilW and sons, New York, 1976. (41 Hatcher, R.A.. "ContraeeptiueTechnoloei,"SUed., lmivington Publishera, NevYork. 1976. (8 Pineus, G.."Cantrol of Fertility" Academic Press. New York. 1965. (6) Roland, M.. "Response to Contraception:' W. 8. Saundera and Co., Philadelphia,
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Journal of Chemical Education
