D Yeates

Risk factors for uterine fibroids: reduced risk associated with oral contraceptives

Risk factors for pathologically confirmed uterine leiomyomas (fibroids) were investigated using data from the Oxford Family Planning Association study, a long term follow up study of women using various methods of contraception. For each of 535 women who had had a fibroid an individual control was selected who matched the patient on age, date of entry into the cohort, and family planning clinic at recruitment and who was alive (and still being followed up) at the date the patient underwent surgery for fibroids. Case-control analysis showed that reproductive experiences were closely linked to development of fibroids. Risk of fibroids decreased consistently with increasing number of term pregnancies; women with five term pregnancies had only a quarter of the risk of women who had had none. Risk also decreased consistently with increasing duration of oral contraceptive use; the risk of fibroids was reduced by some 31% in women who had used oral contraceptives for 10 years. Risk was strongly related to weight: women who weighed under 55 kg had a particularly low risk, and overall the risk rose roughly 21% for each 10 kg increase. Cigarette smoking was associated with a decreased risk of fibroids; smokers of 20 cigarettes a day had a risk roughly two thirds that of non-smokers. These risk factors have all previously been identified as risk factors for endometrial cancer; this strongly suggests that the underlying risk factor is unopposed oestrogen.

Effects of age, cigarette smoking, and other factors on fertility: findings in a large prospective study.

Of 17 032 women taking part in the Oxford Family Planning Association contraceptive study, 4104 stopped using a birth control method to plan a pregnancy on a total of 6199 occasions. The influence of various factors on fertility in these women was assessed by measuring the time taken to give birth to a child. An appreciable inverse relation was observed between age at stopping contraception and fertility both in nulliparous and parous women, but the effect was much greater in the nulliparous women. The most important finding was a consistent and highly significant trend of decreasing fertility with increasing numbers of cigarettes smoked per day; it was estimated that five years after stopping contraception 10.7% of smokers smoking more than 20 cigarettes a day, but only 5.4% of non-smokers, remained undelivered. Some relation was found between fertility and social class, age at marriage, and a history of gynaecological disease, but weight, height, and Quetelets index were without noticeable effect.

Oral contraceptives, cigarette smoking and other factors in relation to arthritis

The data on oral contraceptive use and arthritis in the Oxford-Family Planning Association contraceptive study have been analysed. For rheumatoid arthritis, the rate of first referral to hospital was 0.33 per 1000 woman-years in those who never used oral contraceptives (27 cases), 0.33 per 1000 woman-years in ex-users of oral contraceptives (29 cases) and 0.44 per 1000 woman-years in current users of oral contraceptives (22 cases). Likewise, there was no important association between oral contraceptive use and other forms of arthritis. An unexpected finding was a strong association between referral to hospital for rheumatoid arthritis and cigarette smoking; the rate in women never smoking was 0.27 per 1000 woman-years (34 cases) and in those smoking 15 or more cigarettes per day was 0.64 per 1000 woman-years (19 cases).

NEOPLASIA OF THE CERVIX UTERI AND CONTRACEPTION: A POSSIBLE ADVERSE EFFECT OF THE PILL

The incidence of biopsy-proven cervical neoplasia during a 10-year follow-up was determined in 6838 parous women who entered the Oxford-Family Planning Association contraceptive study while using oral contraceptives and 3154 parous women who entered the study while using an intrauterine device (IUD). Risk factors for cervical neoplasia, continuation of attendance at family planning clinics, and frequency of examination by cervical cytology were similar in the two groups. All 13 cases of invasive cancer occurred in women in the oral contraceptive group; 9 had more than 6 years use of the pill. Both carcinoma-in-situ and dysplasia also occurred more frequently in the oral contraceptive group than in the IUD group, and when the two conditions were considered together there was a trend in incidence with duration of oral contraceptive use. The incidence for all three forms of neoplasia combined rose from 0.9 per 1000 woman-years in those with up to 2 years pill use to 2.2 per 1000 woman-years in those with more than 8 years pill use. Amongst IUD users, there was no such trend in incidence with duration of use: the rate fluctuated around 1.0 per 1000 woman-years. The great majority of cases of invasive cancer were detected by means of cervical smears and were treated while the disease was still curable. Long-term users of oral contraceptives should have regular cervical cytological examination.

Body size and survival in premenopausal breast cancer

The survival experience of 582 women with premenopausal breast cancer was examined to determine whether prognosis was related to body size or to demographic and reproductive factors. During the follow-up period 228 patients died and 18 emigrated or were lost to follow-up. Usual body weight, reported at the time of diagnosis, was a strong predictor of survival, with a statistically significant trend towards lower survival with increasing weight. Height and obesity (Quetelet index) were not significantly related to survival, although the tallest women and the most obese women appeared to fare worst. Other characteristics of prognostic importance were disease stage and reproductive history (women who were older when their first child was born fared better). Women aged 46-50 when diagnosed also appeared more likely to survive but no clear trend with age was evident. Other characteristics of the women including social class, cigarette use and oral contraceptive use were not significantly related to survival probability.

Ovarian neoplasms, functional ovarian cysts, and oral contraceptives.

The incidence of ovarian neoplasms and functional ovarian cysts diagnosed at laparotomy or laparoscopy among the 17,000 women taking part in the Oxford Family Planning Association contraceptive study was investigated. Epithelial cancer of the ovary was only 25% as common among those who had ever taken oral contraceptives as those who had never done so (95% confidence interval 8% to 67%). There was little evidence of any important association between use of oral contraceptives and benign teratoma or cystadenoma. Functional cysts of the ovary occurred much less commonly in women who had recently (in the six months preceding diagnosis) taken combined oral contraceptives (but not in those who had taken progestogen only oral contraceptives) than in those who had never taken oral contraceptives or had taken them in the past. This protective effect was more pronounced for corpus luteum cysts (78% reduction; 95% confidence interval 47% to 93%) than for follicular cysts (49% reduction; 95% confidence interval 20% to 70%). It is estimated that about 28 (95% confidence interval 16 to 35) operations for functional ovarian cysts are avoided among every 100,000 women who take oral contraceptives each year.

Mortality among oral contraceptive users : 20 year follow up of women in a cohort study

OBJECTIVE--To see whether the use of oral contraceptives influences mortality. DESIGN--Non-randomised cohort study of 17,032 women followed up on an annual basis for an average of nearly 16 years. SETTING--17 Family planning clinics in England and Scotland. SUBJECTS--Women recruited during 1968-74. At the time of recruitment each woman was aged 25-39, married, a white British subject, willing to participate, and either a current user of oral contraceptives or a current user of a diaphragm or intrauterine device (without previous exposure to the pill). MAIN OUTCOME MEASURES--Overall mortality and cause specific mortality. RESULTS--238 Deaths occurred during the follow up period. The main analyses concerned women entering the study while using either oral contraceptives or a diaphragm or intrauterine device. The overall relative risk of death in the oral contraceptive users was 0.9 (95% confidence interval 0.7 to 1.2). Though the numbers of deaths were small in most individual disease categories, the trends observed were generally consistent with findings in other reports. Thus the relative risk of death in the oral contraceptive users was 4.9 (95% confidence interval 0.7 to 230) for cancer of the cervix, 3.3 (95% confidence interval 0.9 to 17.9) for ischaemic heart disease, and 0.4 (95% confidence interval 0.1 to 1.2) for ovarian cancer. There was a linear trend in the death rates from cervical cancer and ovarian cancer (in opposite directions) with total duration of oral contraceptive use. Death rates from breast cancer (relative risk 0.9; 95% confidence interval 0.5 to 1.4) and suicide and probable suicide (relative risk 1.1; 95% confidence interval 0.3 to 3.6) were much the same in the two contraceptive groups. In 1981 the relative risk of death in oral contraceptive users from circulatory diseases as a group was reported to be 4.2 (95% confidence interval 2.3 to 7.7) in the Royal College of General Practitioners oral contraception study. The corresponding relative risk in this study was only 1.5 (95% confidence interval 0.7 to 3.0). CONCLUSIONS--These findings contain no significant evidence of any overall effect of oral contraceptive use on mortality. None the less, only small numbers of deaths occurred during the study period and a significant adverse (or beneficial) overall effect might emerge in the future. Interestingly, the mortality from circulatory disease associated with oral contraceptive use was substantially less than that found in the Royal College of General Practitioners study.

Chronic inflammatory bowel disease, cigarette smoking, and use of oral contraceptives: findings in a large cohort study of women of childbearing age.

Since the start in 1968 of the Oxford Family Planning Association contraceptive study 31 women have developed ulcerative colitis and 18 have developed Crohns disease, giving incidences of 0.15 and 0.09/1000 woman years respectively. The incidence of ulcerative colitis in women who were non-smokers on entry to the study was 0.17/1000 woman years and the incidence in smokers was 0.11/1000 woman years. The findings for Crohns disease were entirely different, the corresponding incidences being 0.05 and 0.17/1000 woman years respectively. Both ulcerative colitis and Crohns disease were more common among women currently using oral contraceptives than among those not doing so. Incidences per 1000 woman years for ulcerative colitis were 0.26 in users and 0.11 in non-users; for Crohns disease the incidences were 0.13 and 0.07 respectively. Though the association between the use of oral contraceptives and chronic inflammatory bowel disease cannot be regarded as established, the effects of smoking have been shown consistently in many studies. This observation provides an important clue to the aetiology of chronic inflammatory bowel disease.

Oral contraceptives and stroke: findings in a large prospective study.

Prospective data from the Oxford Family Planning Association contraceptive study suggest only a modest increase in the risk of subarachnoid hemorrhage among oral contraceptive (OC) users. The investigation included 17000 married women recruited to the study in 1968-74 at 25-39 years of age. By January 1984 a total of 192000 woman-years of observation were available for analysis. Data on age past hospital referral for hypertension cigarette smoking and OC use were analyzed for the 13 cases of subarachnoid hemorrhage and 31 cases of nonhemorrhagic stroke (strokes of embolic thrombotic or unknown pathogenesis) observed in the series. The risk of subarachnoid hemorrhage was strongly related to cigarette smoking and past hospital referral for hypertension but weakly related to OC use. On the other hand hypertension or smoking appeared to have little adverse effect on nonhemorrhagic stroke but current OC use emerged as a cleark risk factor regardless of duration of use. Risk of nonhemorrhagic stroke was also examined in relation to type of OC used. No strokes were observed in 9100 woman-years of observation of women using OCs containing less than 50 mcg estrogen while 13 strokes were noted in 39400 years of observation of women using OCs with a higher estrogen dose.

Pelvic inflammatory disease and the intrauterine device: findings in a large cohort study.

The incidence of pelvic inflammatory disease was investigated among parous women taking part in the Oxford-Family Planning Association contraceptive study. Hospital admission rates for acute definite disease were 1.51 per 1000 woman-years among those currently using an intrauterine device (IUD) and 0.14 per 1000 woman-years among those using other methods of birth control (age-standardised relative risk 10.5 to 1 with 95% confidence limits of 5.4 to 1 and 32 to 1). There was little evidence of an increased risk of such disease in ex-users of an IUD. Hospital admission for chronic definite disease, on the other hand, was commoner in ex-users of an IUD than in current users. Acute definite disease occurred somewhat more frequently during the early months of use of an IUD than during the later months. While the rate of such disease was increased in users of each type of device, the highest rate (8.1 per 1000 woman-years) was observed in users of the Dalkon shield. This rate, however, was based on only three affected women.