Preliminary Evaluation of Four Oral Contraceptives Containing only Progestogens

Abstract

Summary: One hundred and seventy-five women took part in a comparative clinical trial of four progestogen-ouly oral contraceptives and were followed for either a year or until treatment was discontinued. Megestrol acetate 0-25 mg. was found to be a very ineffective contraceptive, 21 out of 43 women becoming pregnant. One, three, and four pregnancies occurred during treatment with norethisterone acetate 0'3 mg., norgestrel 0.05 mg., and chodinone 0-5 mg., respectively, corresponding to pregnancy rates of 4, 9, and 12 per 100 woman-years of use.All three effective progestogens were very much less acceptable than modern low-dose combined oral contraceptives. Discontinuation of treatment for medical reasons (particularly menstrual disturbances) during the course of only one year affected 24% receiving norethisterone acetate, 38% receiving norgestrel, and 46% receiving chlormiinone.

Investigations into the mechanism of the antifertility action of minimal doses of megestrol acetate in the rabbit

“…It is unlikely, therefore, that changes in sperm transport through the cervix contribute to the antifertility effects of megestrol acetate under these conditions. This finding is in agreement with some of the more recent animal (Vickery & Bennett, 1969) and clinical (Mears et al, 1969;Gibor et al, 1969) experiments and contrasts with some of the earlier work in this field (Bennett et al, 1967;Roland, 1968 Chang (1966Chang ( , 1967, who observed accelerated egg transport when progestogens were given before, but not after ovulation. In view of these results with such a low dose of megestrol acetate, it is possible that progesterone secretion has a role in the physiological control of egg transport through the oviduct.…”

“…Evidence of ovulation can be obtained in approximately 80% of patients (Martinez-Manautou et al, 1966;Macdonald et al, 1968) and so an effect at pituitary level is unlikely. While changes in cervical mucus resulting in inhibition of sperm penetration have been described (Martinez-Manautou et al, 1966, 1967Mason et al, 1967;Roland, 1968;Zanartu, Pupkin, Rosenberg, Guerrero, Rodriguez-Bravo, GarciaHuidobro & Puga, 1968a), the significance of these changes in relation to the antifertility effects of the regimen has been questioned (Mears et al, 1969;Gibor, Cohen & Scommegna, 1969). It has been proposed that certain endometrial changes may occur (Martinez-Manautou et al, 1967a;Zanartu et al, 1968a) or that the functioning of the corpus luteum may be modified , but neither the precise nature of such changes nor their significance has been established.…”

“…Their studies led to the development of a contraceptive regimen based on continuous administration of synthetic progestogens, in low dosage without added oestrogen (Martinez-Manautou, Cortez, Giner, Aznar, Casasola & Rudel, 1966; Martinez-Manautou, Giner-Velasquez, Cortez-Gallegos, Aznar, Rojas, Guittenez-Najar & Rudel, 1967a; MartinezManautou, Giner-Velasquez & Rudel, 1967b). Many successful trials of this regimen using various progestogens including megestrol acetate have now been reported by other groups of workers (Mason, Cox, Mason & Grant, 1967;Macdonald, Lumley, Coulson & Stitch, 1968;Foss, Svendsen, Fotherby & Richards, 1968; Zanartu, Rodriguez, Pupkin, Salas & Guerrero, 1968b;Howard, Elstein, Blair & Morris, 1969;Mears, Vessey, Andolsek & Oven, 1969;Cox, 1969).…”

Progestagen-Only Oral Contraceptives

“…These changes increase the 'hostility' of the mucus to sperm migration. Norethisterone 0.3 mg has been reported to have a more pronouned antifertility effect on the cervical mucus than dl-norgestrel, 0.05 mg (Mears et al, 1969). Norethisterone 0.3 mg has been reported to have a more pronouned antifertility effect on the cervical mucus than dl-norgestrel, 0.05 mg (Mears et al, 1969).…”

“…Whilst oestrogen-progestagen oral contraceptives produce marked endometrial changes, low dosages of norgestre1 produce less marked changes (Kesserit et al, 1972;Mears et al, 1969;Rice-Wray et al, 1972;Vessey et al, 1972). Although these changes may interfere with nidation it has not been shown that nidation cannot occur.…”