The reduced risk of epithelial ovarian cancer associated with parity and oral contraceptive use suggests that pituitary and/or ovarian hormones or ovulatory events are important in the aetiology of these tumours (Cramer, 1986). Nevertheless, despite extensive study, the influence of menstrual and reproductive factors, with the exception of parity, remains uncertain. In this report, we evaluate menstrual and reproductive characteristics in relation to ovarian cancer risk overall, and in relation to the major tumour histologic subtypes. Our findings are considered in light of several current hypotheses regarding ovarian cancer pathogenesis. Briefly, the incessant ovulation hypothesis suggests that risk is increased by chronic post-ovulatory trauma to the epithelial surface of the ovary, and the tendency to form inclusion cysts (Fathalla, 1971;Casagrande et al, 1979). The gonadotrophin hypothesis proposes that excessive gonadotropin secretion and consequent increases in oestrogen stimulation lead to proliferation and malignant transformation of ovarian epithelium . More recent hypotheses have suggested a role for chronic ovarian inflammation (Ness, 1999), androgens and progesterone (Risch, 1998), and the possibility that pregnancies reduce risk by clearing transforming cells from the ovaries (ovarian clearance) (Adami et al, 1994). METHODSWe conducted a population-based, case-control study of epithelial ovarian cancer in eastern Massachusetts (MA) and New Hampshire (NH). The methods used have been previously described Harlow et al, 1998). Briefly, 1033 potentially eligible case women (ages 20 to 74) were ascertained between May 1992 and March 1997 through state-wide cancer registries (NH, MA) and hospital tumour boards (MA). After exclusion of patients who had nonepithelial tumours (n = 52), and those who had died (n = 91), moved out of state (n = 27), had no telephone (n = 24), or did not speak English (n = 14), 825 case women were eligible for the study. Physicians denied permission to contact 126 (14%) of these women, and 136 (16%) of women declined to participate. This analysis is based on 563 cases of epithelial ovarian cancer, including lesions of borderline malignancy.Control women were identified primarily by random digit dialing (RDD) (Waksberg, 1978), and matched to case women by age (within 4 years) and telephone sampling unit. Of approximately 5400 residential households contacted, 10% declined to provide a household census, and 80% provided a census, but lacked a potentially eligible control subject. In the remaining 10% of households, a potentially eligible control was identified. 72% of the potential control women agreed to participate in the study. In MA, control women of age 60 or older were randomly chosen from Town Books, and matched to case women by age and precinct. Of 328 control women selected from Town Books, 21% Summary We assessed menstrual and reproductive factors in relation to ovarian cancer risk in a large, population-based, case-control study. 563 cases in Massachusetts and New Hampsh...

Uterine leiomyomas are reported to be the most common benign gynecologic tumors affecting premenopausal women, and they are often associated with considerable morbidity. The purpose of this study was to identify risk factors for uterine fibroids among women undergoing tubal sterilization. Cases comprised women aged 17-44 years whose uterine fibroids were first visualized at the time of tubal sterilization (1978-1979 or 1985-1987) or who reported a history of uterine fibroids (n = 317). Controls were randomly selected from women with no laparoscopic evidence of or history of fibroids (n = 1,268). Adjusted odds ratios were estimated using unconditional logistic regression separately for White (n = 1,235) and African-American (n = 350) women. Risk factors for White women included: age 40-44 years (odds ratio (OR) = 6.3; 95% confidence interval (CI): 3.5, 11.6), > or =5 years since last delivery (OR = 1.9; 95% CI: 1.1, 3.1), lifetime cigarette smoking of > or =1 pack/day (OR = 1.6; 95% CI: 1.1, 2.3), menstrual cycle length of >30 days (OR = 1.6; 95% CI: 1.1, 3.3), and menstrual bleeding for > or =6 days (OR = 1.4; 95% CI: 1.0, 2.0). Parous women were at reduced risk compared with nulliparous women (OR = 0.2; 95% CI: 0.1, 0.3). Advancing age was the only significant risk factor for African-American women (ages 40-44 years, OR = 27.5; 95% CI: 5.6, 83.6). Current oral contraceptive use and elective abortion were not associated with fibroids.

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Overall, our findings provide little support for the hypothesis that prenatal exposure to DES influences the psychosexual characteristics of adult men and women.

In vitro and clinical data suggest that cisplatin and carboplatin resistance may be overcome in some cases by dose escalation, although clinical toxicities limit this approach. Administration of platinum analogues in combination is an alternative dose-intensification strategy that has been little studied. The cytotoxicities of cisplatin (CDDP), carboplatin (CBDCA), and tetraplatin (TP, ormaplatin) alone and in combination were assayed by inhibition of the clonogenic survival of human ovarian-carcinoma cell lines (a) from an untreated patient (A2780), (b) selected for CDDP resistance in vitro (2780-CP70), and (c) from patients presenting with clinically refractory disease (OVCAR3, OVCAR10). The sensitivity patterns of these cell lines to platinum analogues were consistent with the existence of at least two platinum-resistance phenotypes - one being moderately resistant to CDDP and CBDCA but highly resistant to TP and the other being highly resistant to CDDP and CBDCA but only partially cross-resistant with TP. Effects of drug combinations were determined by median-effect analysis. Interactions between platinum analogues were variable in different cell lines. Synergistic cytotoxicity was apparent for the CDDP-CBDCA combination in the A2780 and OVCAR-3 cell lines and for the CDDP-TP combination in 2780-CP70 and OVCAR-3. Strong antagonistic effects were seen for CBDCA-TP in 2780-CP70. Platinum analogues showed additive effects in the remaining cell lines. These data suggest that there may be distinct sensitivity phenotypes for platinum-analogue combinations. The demonstration of in vitro synergy between platinum analogues supports their combined clinical use.