Cancer incidence in a cohort of infertile women

Modan B; Ron E; Lerner-Geva L; Blumstein T; Menczer J; Rabinovici J; Oelsner G; Freedman L; Mashiach S; Lunenfeld B

doi:10.1093/oxfordjournals.aje.a009397

General Gynecology · Cancer and Fertility

Cancer incidence in a cohort of infertile women

Modan B, Ron E, Lerner-Geva L, Blumstein T, Menczer J, Rabinovici J, Oelsner G, Freedman L, Mashiach S, Lunenfeld B

Published June 1998 American Journal of Epidemiology, 147(11), 1038-1042

DOI 10.1093/oxfordjournals.aje.a009397 PMID 9620047

RRM Academy Synopsis

Infertile women with unopposed estrogen had excess endometrial cancer

Women evaluated for infertility developed 21 endometrial cancers where 4.3 were expected, in a cohort study of 2,496 Israeli women followed 21.4 years on average. The excess was prominent in 967 women with unopposed estrogen (enough estrogen, too little progesterone). Of all 2,496 women, 1,309 received ovulation-inducing drugs. Ovarian cancer risk was similar in treated and untreated women.

Key Findings

Among 2,496 women evaluated for infertility, 143 cancers occurred through 1991 where 116.1 were expected, a standardized incidence ratio (SIR) of 1.2 (95% confidence interval (CI) 1.0-1.5).
Endometrial cancer: 21 cases versus 4.3 expected (95% CI 3.0-7.4). Ovarian cancer: 12 versus 7.2 (SIR 1.6, 95% CI 0.8-2.9). Breast cancer: 59 versus 46.6 (SIR 1.3, 95% CI 0.96-1.6).
Among 967 women with adequate estrogen but progesterone deficiency, 13 endometrial cancers occurred against 1.4 expected (SIR 9.4, 95% CI 5.0-16.0). Other sites were not significantly elevated there.
Ovarian cancer SIR was 1.7 among the 1,309 women treated with ovulation-inducing drugs and 1.6 among the 1,187 untreated women. Endometrial SIR was higher with treatment, although not significantly.
Six ovarian cancers occurred among 908 women treated with clomiphene citrate alone against 2.3 expected (SIR 2.7, 95% CI 0.97-5.8). The difference from the untreated group (SIR 1.6) was nonsignificant.

Interpretation

The study followed women from one Israeli medical center. Cancers came from national registry linkage and were compared with national rates. The authors' sensitivity analyses found that nulliparity (no prior births), obesity, contraceptive use and hysterectomy could not fully explain the endometrial excess. A much higher rate of nulliparity might explain the ovarian result. Hormonal status was classified by clinical criteria. The authors describe the study power as limited. They conclude that the data do not suggest ovulation-inducing drugs raise ovarian or breast cancer risk, and that a role in endometrial cancer cannot be completely excluded.

RRM Context

Progesterone is made after ovulation, so a shortage can mean that ovulation is disturbed. Restorative reproductive medicine looks for the cause and treats it. The authors cite the known link between unopposed estrogen and endometrial cancer.

Our editorial summary of this paper, not the article's abstract.

Abstract

Among 2,496 infertile Israeli women treated between 1964 and 1974, 143 cancer cases were observed as compared with 116.1 expected (standardized incidence ratio (SIR) = 1.2, 95% confidence interval (CI) 1.0-1.5) through 1991. Site-specific analysis revealed 12 ovarian cancers versus 7.2 expected (SIR = 1.6, 95% CI 0.8-2.9), 21 endometrial cancers versus 4.3 expected (SIR = 4.85, 95% CI 3.0-7.4), and 59 breast cancers versus 46.6 expected (SIR = 1.3, 95% CI 0.96-1.6). Sensitivity analysis revealed that confounding was unlikely to explain the raised risk of endometrial cancer, but nulliparity might explain the increased risk of ovarian cancer. The excess of endometrial cancer was prominent among patients with normal estrogen production but progesterone deficiency (SIR = 9.4, 95% CI 5.0-16.0). The risk for ovarian cancer was similar among the total groups of treated and untreated patients (SIR = 1.7 vs. 1.6). The standardized incidence ratio for endometrial cancer was higher among the treated group than the untreated group, although not significantly. Treatment with ovulation-inducing drugs does not appear to increase the risk for ovarian cancer, but its role cannot be completely excluded.

Topics

General Gynecology › Cancer and Fertility › Hormone Sensitive Cancer and Reproductive Care · Reproductive Endocrinology › Ovarian Hormones › Progesterone

Lori Freedman

L Freedman

PMID 9620047 9620047 DOI 10.1093/oxfordjournals.aje.a009397 10.1093/oxfordjournals.aje.a009397 Modan et al. 1998, Modan 1998

Keywords

Adult, Breast Neoplasms/epidemiology, Clomiphene/therapeutic Use, Endometrial Neoplasms/epidemiology, Estrogens/metabolism, Female, Fertility Agents, Female/therapeutic Use, Genital Neoplasms, Female/epidemiology, Gonadotropins/therapeutic Use, Humans, Incidence, Infertility, Female/drug Therapy/metabolism/physiopathology, Israel/epidemiology, Middle Aged, Ovarian Neoplasms/epidemiology, Progesterone/metabolism, Risk Factors, Estrogens, Fertility Agents, Female, Gonadotropins, Clomiphene, Progesterone

Cancer incidence in a cohort of infertile women

Infertile women with unopposed estrogen had excess endometrial cancer

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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Keywords