Mass screening for endometrial cancer directed in risk groups of patients with diabetes and patients with hypertension.

BACKGROUND: The interest in mass screening programs for the early detection of endometrial cancer (EC) has grown with the rising incidence of this disease. Preliminary programs directed at asymptomatic women with only one risk factor, i.e. age, have not been cost-effective. METHODS: In the current study, 597 asymptomatic women from 45-69 years of age with diabetes and/or hypertension were screened by Vabra (Berkeley Medevices Inc., Berkeley, CA) aspiration. RESULTS: Among the women with diabetes, 6.3% preinvasive lesions of the endometrium were found. This is significantly more than the rate among women with hypertension, which was 1.3% (P < 0.01). CONCLUSIONS: Regular mass screening programs for the early detection of EC should be directed at asymptomatic diabetic women 45 years of age or older. This study does not indicate that similar screenings would be effective for women with hypertension.

Age at menarche, urine estrogens and breast cancer risk.

In 511 nulliparous women aged 15-19 years and 347 aged 30-39, an analysis has been undertaken of the relationship of urine concentrations of the three principal estrogens to age, age at menarche and Quetelet's index of adiposity. The analysis was undertaken by means of multiple regression, controlling for each of the 12 centers from which the data originated, as well as for the other study variables. In the younger women, age was strongly and positively related to concentrations of E1 and E2 and less so to E3. In the age group 30-39, follicular phase specimens showed positive relationships with age for all three fractions but luteal specimens did not. Age at menarche showed inverse relationships to levels of E1 and E2 which were significant in the younger but not in the older age group. The associations of estrogens with Quetelet's index were weak and not statistically significant. The data suggest that women whose menarche occurs early not only have a longer duration of exposure to estrogens during years which are probably important in the initiation of breast cancer but, in addition, their exposures are at a higher level during those years and probably at later ages also. These observations support the hypothesis that the mechanism of the association of early menarche with breast cancer risk is via the association of both with estrogen stimulus.

Age at menarche, probability of ovulation and breast cancer risk.

An analysis is undertaken of the frequency of ovulation in 17 groups of women aged 15 to 19 who had been the subjects of other studies. A urine specimen of at least 8 h accumulation had been provided on the 20th or 21st day of a menstrual cycle by 681 women. Analysis is restricted to 431 specimens which had been collected between 11 and 3 days prior to the onset of the subsequent menstrual period. A pregnanediol concentration of less than 1 mg per litre in such a specimen was taken as evidence that the cycle was anovular. The probability of a cycle being anovular was inversely and significantly related to the number of years since menarche, and, with years since menarche held constant, was positively but not significantly associated with age at menarche. This observation indicates that women with early menarche do not have a longer duration of exposure to anovular cycles than do those whose menarche is delayed, and that variation in the duration of exposure to post-menarcheal anovular cycles does not explain the association of breast cancer risk with early age at menarche. The 17 groups of women were classified into four categories according to ethnic origin and breast cancer incidence in the populations from which they derived. Anovular cycles were not more common in the high-risk groups; indeed, the two centers in the lowest risk category had the highest proportion of anovular cycles.

Cytologic evidence of the association of condylomatous lesions with dysplastic and neoplastic changes in the uterine cervix.

Cytologic smears were obtained from 272 women shown, during a mass screening program, to have histologically proven severe dysplasia, carcinoma in situ or invasive squamous cell carcinoma of the uterine cervix. These smears were scrutinized with special attention to the detection of the cytologic pattern recently established as diagnostic of condyloma virus infection in the genital tract. The results disclosed positive cytologic findings in a considerable percentage of the smears studied, in contrast to an absolute failure to demonstrate any cytologic evidence of the presence of genital herpesvirus infection. The frequency figures of the positive findings were in accordance with the previously established frequency figures of histologically verified condylomatous lesions, thus confirming the applicability of the cytologic criteria used. The significance of the findings is discussed in the light of cervical carcinogenesis, and the conclusion is drawn that one should seriously consider the possibility that the virus behind the condylomatous lesions is the agent responsible for, or contributing to, the development of uterine cervical carcinoma.

Risk of cervical cancer among an electrocoagulated population.

In Finland an organized mass screening program covers the total female population. Based on the material (429,832) from a nationwide mass screening registry it was estimated that the female population not subjected to electrocoagulation of the uterine cervix (362,511) had a sixfold risk of frankly invasive carcinoma, a fourfold risk of carcinoma in situ or dysplasia of high degree, and a twofold risk of dysplasia of low degree as compared with the female population subjected to electrocoagulation of the uterine cervix (67,321). The relative risk of cervical lesion varied by cytologic diagnosis, marital status, and Trichomonas vaginalis.

Clinical investigation of the biological effects of a new combination low-dose oral contraceptive ('Ovostat E').

PIP: A low-dose contraceptive containing 1 mg of lynestrenol and .05 mg of ethinyl estradiol was studied over 12 cycles in 11 healthy fertile women volunteers. The subjects were aged 20-30 years. Measurements were taken of urinary luteinizing hormone (LH), pregnanediol, and estrogen, and serum progesterone and estradiol values; in addition, on a fixed schedule during treatment, the 3rd, 5th, 7th, and 12th months, vaginal smears and endometrial biopsies were taken, along with SGOT and SGPT determinations. According to determinations, ovulation was inhibited during every cycle tested. A clear estrogenic effect was evident in the karyopyknotic index, during cycle 3, at the beginning of the cycle which became a progestational effect around Day 13 (biphasic). In cycle 6, the indexes of cytology decreased, but during Cycle 12, they rose a bit again. Basal body temperature during treatment was monophasic. Cervical mucus assessed by spinnbarket during treatment was low and arborization absent. The SGOT and SGPT liver function tests were within normal values in all cycles in 7 women; 4 showed clearly higher levels in Cycles 3 and 12. None of the cycles showed the high midcycle urinary excretion of LH. No significant side effects were reported. Examination of the endometrial biopsies showed a drug effect in all cases and there was no secretory activity in any of the samples. These findings confirm clinical results that show this low-dose combination to be an effective contraceptive agent.^ieng

The effect of treatment with a low-dose progestagen (Lynestrenol) on hormonal cytology.

The effect of continuous, low-dose progestagen therapy on endogenous oestrogen production and ovulation in women, was investigated in terms of vaginal cytology. The phase contrast method was used to establish the karyopknotic index from 482 smears from patients using lynestrenol 0.5 mg for oral contraception. The results are presented as the mean of karyopyknotic indices, with standard deviation and standard error of the mean, scored over each three day period of the menstrual cycle, and, in the case of delayed menstruation, over longer periods throughout the protracted cycle. Graphically, the results are shown as average levels compared to controls. Our results show that in patients who have used the preparation for a maximum of three months, cyclic oestrogen production varies only slightly, the mean being within the lower limit of normal and suggesting FSH suppression. In patients who use the preparation for longer periods, the karyopyknotic index becomes similar throughout the cycle to that of controls, being clearly biphasic and generally suggestive of ovulation. In the first group, delayed menstruation seems to be caused mainly by transient FSH suppression. When it occurs in the group treated over a longer period, the disorder appears to be caused by a normo- or hyperoestrogenic, anovulatory condition, due initially to LH suppression with FSH supression setting in later, if the disorder persists longer.

The effect of oral contraceptives on hormonal cytology.

PIP: The effects of different oral contraceptive combined preparations (Serial, Ovanon, Delpregnin, Lyndiol 2.5, Ovulen mite, Primovlar, Gentrol, and Anovlar) on vaginal cytology during different phases of the menstrual cycle were studied. The karyopyknotic index was determined by phase contrast in 1301 patients and in 2213 controls. The results revealed great differences in estrogen activity and individual modes of action of progestin based on the cyclical pattern. It was established that vaginal cytology is an applicable and convenient method of comparing biological and especially estrogenic activities of different OCs as well as the reciprocal effect of different progestational steroids, and it is recommended that this method should be used in testing new preparations.^ieng