A multicentre comparative study of serum lipids and lipoproteins in four groups of oral combined contraceptive users and a control group of IUD users

A prospective clinical trial was conducted in three centres to assess the effects of the type and dose of progestogen, the dose of estrogen and the progestogen-to-estrogen ratio of oral contraceptives on lipid metabolism. The preparations selected contained levonorgestrel 250μg + ethinyl estradiol 50μg (Neogynon), levonorgestrel 250μg + ethinyl estradiol 30μg (Eugynon 30), levonorgestrel 150μg + ethinyl estradiol 30μg (Microgynon) or norethisterone acetate 1mg + ethinyl estradiol 50μg (Minovlar).

Four-hundred-and-seven premenopausal women were randomly assigned to one of the four pill groups and compared to a control group of 119 users of a CuT220c intrauterine device. Total cholesterol, HDL-cholesterol, LDL-cholesterol and total triglycerides were monitored and the analysis includes the data of those who were followed over 48 weeks, 241 OC users and 87 IUD users.

250μg of levonorgestrel were found to induce more unfavourable lipid changes in terms of atherosclerotic risk than 1mg of norethisterone acetate. Levonorgestrel was found to have a dose-effect on HDL-cholesterol and LDL-cholesterol serum levels, while ethinyl estradiol had a dose-effect on serum triglycerides. HDL-cholesterol was related to the progestogen-to-estrogen ratio. Most of these findings were consistent across centres. Finally, some comments are made on the implications of the study results on the design of future lipid studies.     

Depot-medroxyprogesterone acetate (dmpa) and risk of edometrial cancer

This is a report of results from a case-control study of the relationship of the long-acting progestational contraceptive, depot-medroxyprogesterone acetate (DMPA) to risk of endometrial carcinoma. Prior use of DMPA and information on known and suspected risk factors for endometrial cancer were ascertained in personal interviews with 122 women with histologically confirmed disease and 939 controls selected from 2 hospitals in Bangkok and 1 in Chiang Mai, Thailand. Based on 3 exposed cases and 84 exposed controls, the relative risk of endometrial cancer was estimated to be 0.21 (95% confidence interval = 0.06,0.79) in women who had ever used DMPA (but who had not first used DMPA in the year prior to diagnosis). All 3 exposed cases had also received estrogens pre-menopausally. Exposure to such estrogens enhanced risk of endometrial cancer and reduced the apparent protective effect of DMPA. Although based on small numbers of exposed women, the protective effect of DMPA appeared to last for at least 8 years after cessation of use. The reduction in risk of endometrial cancer is at least as great for DMPA as for combined oral contraceptives.     

Alcohol,tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies,including 58,515 women with breast cancer and 95,067 women without the disease

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.     

A clinical and metabolic study of norethisterone oenanthate in Thai women

Norethisterone oenanthate was given as an injectable contraceptive to 126 Thai women. Only healthy informed volunteers aged 18–35 years were admitted to the study. One ml of oily solution containing 200 mg of steroid was administered into the gluteal muscles. The first injection was given during days 1–5 of a normal menstrual period. The second, third and fourth injections were given at eight-week intervals and were followed by subsequent injections at 12-week intervals. All injections were given within seven days of the scheduled date. Volunteers were instructed to record any vaginal bleeding in diary cards. At each visit, weight, blood pressure and menstrual bleeding were recorded. Complaints and adverse effects were also noted.Prior to admission for study, an oral glucose tolerance test (OGTT), serum transaminase, cholesterol and triglycerides were simultaneously studied in 21 women and then repeated at three, six and twelve months.The 12-month continuation rate was $\text{63}\text{100}$ women-years with 5 accidental pregnancies. Two pregnancies occurred during the second injection intervals and the other three pregnancies occurred during the third, fourth and fifth injection intervals. The 12-month study revealed $\text{11}\text{100}$ and $\text{25}\text{100}$ women-years of amenorrhea and heavy bleeding, respectively.There was a statistically significant increase in the serum glucose tolerance test (P < 0.05) at the 30-minute time intervals after 12 months of use, but the areas under the curves were within normal limits. The total cholesterol and triglycerides showed a significant transient decrease (P < 0.01) at the third month of study and returned to normal after 6 months.