Combined oral contraceptives (OCs) have nearly total efficacy when correctly used and good overall tolerance among most women under 40, but there are several significant contraindications to their use. Women with hypertension, hyperlipidemia, diabetes, minor mastopathy, or premenstrual tension should not use OCs containing estrogen. Macroprogestational OCs administered generally 20 days out of 28 are useful when an antiestrogen effect is sought or when metabolic anomalies are to be avoided. An antiestrogen effect may be desired for women over 40 suffering from relative or absolute hyperestrogenism, or for women with premenstrual syndrome, menorrhagia related to endometrial hyperplasia or other menstrual problems, or benign mastopathies. An antiestrogen effect may also be desired to prevent cellular pathologies common after age 40. Some anomalies of metabolism, blood pressure, and coagulation persist in users of combined OCs regardless of the dose or the compounds used in the formulation. Progestins derived from testosterone were the first to be used in contraception and provide good cycle control and antigonadotropic activity, along with a powerful antiestrogen effect. But they may have metabolic side effects and cause signs of hyperandrogenism. Progestins derived from progesterone have been studied in health women and in those with different risk factors. Chlormadinone acetate has been used in women at high vascular risk, and promegestone has been used in women with fibrocystic breast disorders. A study was also done on 36 healthy women for 6 months using nomegestrol acetate. The preliminary results were good but the numbers of women were small, they had no metabolic risk factors, and the treatment periods were short. The results thus cannot be extrapolated to subjects at risk or for use during longer periods. The only observed modifications (essentially declines in apoprotein A1 and elevation of antithrombine) were probably attributable to the decline in average estradiol levels and without significance for risk. A disadvantage of these methods is that they have not been authorized for marketing as contraceptives in France and no Pearl index is available. Although the incidence of menstrual problems is not well known, such problems appear to be relatively frequent. The hypoestrogenism often sought for women with gynecological pathologies is not necessarily desirable for women using these methods because of metabolic problems or age over 40. A sufficient estradiol level protects against premature bone loss and has important metabolic effects including better production HDL cholesterol. 18 women who experienced menstrual problems with macroprogestational contraceptives were given 5 mg/day of nomegestrol acetate in combination with transdermally administered estradiol. Clinical and metabolic tolerance were excellent, and no pregnancies occurred. Further study is warranted.