Initially I would like to say that, based on my 28 years of gynecologic practice, the best of all available contraceptive methods continues to be the "old Pill", that is, the oral hormonal contraceptives. And, to my point of view, this observation about the oral contraceptives is valid considering their highly positive benefit/risk relation and, obviously, the high efficacy of the method. These products have been used for about 40 years and constitute some of the most studied and researched medicines to date. The fact is that, for most women, the contraceptive security, tranquility and comfort provided by the oral hormonal contraceptives by far outweigh the rare and occasional risks and problems that eventually may occur. We must also consider that, during the last decades, the hormonal doses contained in these medicines have been considerably reduced, and new synthetic hormones, better tolerated and with fewer side effects, have also been developed and utilized in the more recent products. In this way, the "Pill" is constantly evolving and being improved.

Let us see, for instance, the reduction in the estrogen dose of the oral contraceptives that took place in the last three decades. Up to 1974, the usual dose of ethinyl estradiol contained in each tablet was 0.05mg ( considered excessive according to the desired safety standards, mostly regarding the occurrence of some important, though fortunately rare, side effects ). However, in that same year it was already possible to successfully reduce the daily ingestion of ethinyl estradiol to 0.03mg, preserving the same efficacy with excellent tolerability and considerably fewer side effects. Recently a new generation of oral contraceptives was developed, in which the daily ingestion of ethinyl estradiol was once again successfully reduced to 0.02mg ( the low-dose "Pills" ). Reductions in the progestogen doses of these medicines have also been done. Therefore, as I have already said, we can easily verify that the "Pill" actually has evolved and has been considerably improved throughout the years.

And, very recently, another product was released reducing once again the aforementioned daily ethinyl estradiol dose to 0.015mg, together with a reduction in the respective dose of the progestin associated to it. In order to counterbalance this considerable reduction without lessening the contraceptive efficacy, this very new "Pill" is to be taken in series of 24 days ( instead of the usual 21 days ) and the interval between the series was reduced to 4 days ( instead of the usual 7 days ). Nevertheless, I want to make it clear that this product is too new, the dosage is too low and, personally, I still do not have all the necessary information regarding its real contraceptive security. Though it seems to be effective if taken in this new regimen of administration, I believe this new oral contraceptive still demands more clinical studies.

All oral hormonal contraceptives consist of combinations of the already mentioned synthetic estrogen ethinyl estradiol with one of the several existing progestogens or progestins ( synthetic "progesterones" ). Of all progestogens or progestins that have been utilized in these products, the more important ones are the levonorgestrel, norethysterone, cyproterone, desogestrel and gestodene. The newest generations of "Pills" contain preferably the progestogens desogestrel and gestodene, since some of their general metabolic effects seem to be smaller and more favourable than those of the other progestins. This implies an improved general metabolic profile.

The oral contraceptives that combine the estrogen ethinyl estradiol with the progestogen cyproterone are specifically indicated for women with hypertrichosis or slight hirsutism ( excessive growth of hair on several parts of the body ) and acne, due to the well-known anti-androgenic effect of cyproterone. This happens because cyproterone has the property of inhibiting the androgenic action on almost all androgen-receptors of the body, among them obviously the hair follicles. As a consequence, the hypertrichosis/hirsutism and acne can be reduced under the effect of "Pills" containing cyproterone. Nevertheless, this treatment must only be prescribed after the completion of a careful investigation of these androgenic or hyperandrogenic manifestations intended to correctly diagnose the real origin of this increased growth of hair on several parts of the female body.

Almost all oral contraceptives used along the last decades are considered "combined" and "monophasic." "Combined Pills" are those in which all tablets in a series contain both estrogen and progestogen. "Combined monophasic Pills" are those in which the respective doses of estrogen and progestogen contained in all tablets along the series are the same. Whenever the respective dose of estrogen or progestogen varies along a series, implying the existence of two or three different kinds of tablets in it, these "Pills" are said to be "biphasic" or "triphasic" ones, and there are a few products of this kind in the market. Nevertheless, as I have already said, almost all modern oral contraceptives are "combined and monophasic", that is, the daily hormonal ingestion is the same along the usual 21 days that constitute each series of the "Pill."

Needless to remark that this hormonal composition varies according to each specific kind of oral contraceptive available in the market - that is to say, with each product. Therefore, there are and there have been lots of different contraceptive pills, making use of different estrogenic-progestogenic associations in many different respective doses. This great existing number of different hormonal contraceptives, making use of different hormones in varying doses, allows us to get close to "choosing the ideal 'Pill' for each woman", individualizing the prescription as close as possible.

The "combined" oral hormonal contraceptives work by means of three basic mechanisms:

1) they interrupt most of the ovarian function due to an interference in the intricate feedback mechanisms of the hypothalamus-pituitary-ovaries axis. The usual pattern of secretion of FSH ( follicle stimulating hormone ) and LH ( luteinizing hormone ) by the pituitary is considerably altered. As a result, the development of the ovarian follicles is interrupted at their first stages of growth, and no one of them reaches the stage of a mature follicle. The pituitary ovulatory peak of LH is also abolished. This interference in the hypothalamus-pituitary-ovaries axis constitutes the main mechanism of action of the hormonal contraceptives, resulting on the suppression of ovulation;

2) they produce specific alterations in the endometrium ( the mucosa that covers the interior of the uterine cavity ) which, in the case of an eventual failure in the inhibition of ovulation, creates considerable difficulty for the implantation of the fertilized egg;

3) they produce a thickening of the uterine cervix mucous secretion, thus making it difficult for the ascension of the spermatozoa inside the uterus.

In this way, the "combined" oral contraceptives present a main contraceptive mechanism ( the interruption of the ovarian function and the consequent inhibition of ovulation ) and two other complementary mechanisms ( which, isolated, are not reliable but, associated with ovulatory suppression, increase the final contraceptive efficacy ).

As it is well known, the usual oral contraceptives are taken in series of 21 days, with an interval of 7 days of rest between the series. In the artificial cycles induced by the "Pill", this interval is intended for imitating the usual hormonal fall that takes place at the end of each natural cycle ( which the female organism is physiologically used to ) and for allowing menstruation to come ( though the menses that come after each series of the "Pill" are artificial, since they are caused just by this periodic interruption in the use of the hormonal contraceptive ). Considering that the hormonal contraceptives inhibit the ovarian function, it is advisable that, at least once a year, women using the "Pill" stay one or two cycles without taking it, in order to avoid a prolonged inhibition of the aforementioned hypothalamus-pituitary-ovaries axis.

As to the present proposal of abolishing menstruation through the continuous use of hormones, my opinion is clearly expressed in my article "Uninterrupted use of hormonal contraceptives for menstrual suppression: why I do not recommend it", published at the Museum of Menstruation and Women's Health ( www.mum.org ).

Before finishing, something else must be added about the oral hormonal contraceptives. In the beginning of this article, I expressed my opinion that they are the best and the safest of all contraceptive methods, because the benefits provided by their use by far outweigh some risks and problems that rarely may occur. But besides the great benefit of their high contraceptive efficacy allied to the simplicity of their use, other positive aspects related to the use of the "combined" hormonal contraceptives have been demonstrated over the last years. They consist basically on a reduction in the incidence of ovarian and endometrial cancer.

The minor incidence of ovarian cancer in women who have used the "Pill" for a long time may be related precisely to the inhibition of ovulation. Though the subject is still controversial, it is possible that very frequent ovulations may be one of the many factors that predispose women to some kinds of ovarian malignant neoplasias. As to the reduction in the occurrence of endometrial cancer, the reason is that, during the use of the "combined type" of hormonal contraceptives, women take an association of estrogen and progestogen for three weeks each cycle. As a result, the progestogenic component of these "Pills" taken for 21 days along each cycle prevents the development of endometrial hyperplasias, a very common group of pathologies of which some types can be precursors of endometrial cancer.

P.S.: After the writing of this article a new progestogen named drospirenone was released and, with it, new oral contraceptives associating drospirenone with the usual estrogen ethinyl estradiol. So, see my new article "Drospirenone Oral Contraceptives" ( September 2007 ).

Nelson Soucasaux is a gynecologist dedicated to Clinical, Preventive and Psychosomatic Gynecology. Graduated in 1974 by Faculdade de Medicina da Universidade Federal do Rio de Janeiro, he is the author of several articles published in medical journals, and of the books "Novas Perspectivas em Ginecologia" ("New Perspectives in Gynecology") and "Os Órgãos Sexuais Femininos: Forma, Função, Símbolo e Arquétipo" ("The Female Sexual Organs: Shape, Function, Symbol and Archetype"), published by Imago Editora, Rio de Janeiro, 1990, 1993.

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