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Arachidonic acid metabolites produced by primary cultures of human endometrial cells derived from biopsies obtained before and after exposure to 20 micrograms/day levonorgestrel for 84 +/- 1 days were analysed by reverse phase HPLC. This revealed a significant increase in PGF1 alpha and an epoxide metabolite upon levonorgestrel stimulation. The proportion of epoxide metabolite, PGF1 alpha and PGE2 were positively correlated with serum levonorgestrel levels while HETES, PGE2 and epoxide were similarly correlated with serum oestradiol. The extent of intermenstrual bleeding during exposure to levonorgestrel was correlated with the proportion of epoxide and HETES products in vitro which is discussed in relation to their physiological function.

The efficacy and acceptability of a levonorgestrel-releasing intravaginal ring (IVR) for contraception was assessed in a British cohort studied as part of a multicentre, multinational clinical trial performed under the auspices of the World Health Organisation. One-hundred-and-fifty women took part in the study in two UK centres and completed 1417.5 months of method use. Fifty-nine women discontinued use of the IVR before the end of one year giving an overall discontinuation rate of 39.9 per 100 woman-years. The discontinuation for pregnancy with the ring in situ, was 3.0 per 100 woman-years (life table analysis). Menstrual disturbance, vaginal problems and involuntary expulsion resulted in discontinuation rates of 8.9, 8.4 and 1.6 per 100 woman-years, respectively. This method is an acceptable and effective method of contraception for women.

Lipid concentrations were measured in 74 blood samples from 61 women who had been using the injectable contraceptive Norigest (norethisterone oenanthate) for between 2 to 4-1/2 years. There were no significant changes in the concentrations of total cholesterol, total triglycerides and low density and very low density lipoprotein cholesterol but high density lipoprotein cholesterol was significantly reduced. The reduction in serum HDL-C levels was not correlated with either the serum norethisterone concentrations or the length of use of Norigest nor was it affected by obesity or smoking.

A clinical trial was carried out in which Norigest (200 mg norethisterone oenanthate) was administered by intramuscular injection every 56 days into 383 women studied for 5,521 woman-months of use. No pregnancies occurred. Continuation rates at the end of one, two and three years were 76.6%, 63.7% and 33.8%. Only minor side-effects were recorded. After one year of use, 20.1% women had gained more than 2 kg in weight and 14.8% had lost more than 2 kg. There was marked disruption of the menstrual pattern and irregular bleeding was the major cause of discontinuation. In 38% of the injection intervals analysed, women were amenorrhoeic. Norigest proved an effective and acceptable method of fertility control.

Fifteen healthy subjects used a contraceptive device, namely an intravaginal ring releasing 20 micrograms levonorgestrel daily, for 12 weeks. High, low and very low density fractions of cholesterol, triglyceride and phospholipids were measured, together with oral glucose tolerance before and after 12 weeks of use. There were no significant differences in any of the plasma lipid fractions or in glucose tolerance.

There is concern that the breast-fed infant whose mother is receiving intra-muscular progestogens for contraception will be exposed to significant quantities of the steroid. Norethisterone levels in maternal serum and milk were studied throughout an injection interval after intramuscular administration of 200mg norethisterone oenanthate. Milk samples were taken at the beginning and at the end of the feed. Norethisterone concentrations in milk were very much lower, but declined more slowly, than serum concentrations. Post-suckling concentrations were higher than pre-suckling concentrations. Experiments in adults receiving an oral dose of norethisterone in cow's milk comparable to that ingested by an infant in a day resulted in low serum levels. It is concluded that only very low concentrations of norethisterone would be present in the infant's circulation.

The return of ovarian activity was studied in 20 women who had discontinued norethisterone oenanthate after using the injectable contraceptive for 6 months to 5 years. Follicular activity returned within 70 days of discontinuing in four women and within 90 days in a further seven. In only 4 women was the return of follicular activity associated with a rise in the serum progesterone level. The serum norethisterone concentration was usually less than 1 ng/ml at the time of return of ovarian activity and was lower in women in whom ovarian activity returned before day 90 than in those in whom it returned after day 90. Of 40 women who discontinued norethisterone oenanthate, pregnancy occurred in 14 women within 12 weeks of discontinuing and in 21 (52.5%) within 6 months. The findings suggest that there is no impairment of fertility in women using norethisterone oenanthate.