Long-term Follow-up After Endometrial Ablation in Finland: Cancer Risks and Later Hysterectomies.

OBJECTIVE: To study the risk of endometrial cancer and breast cancer and the hysterectomy rate after endometrial ablation. METHODS: In this retrospective cohort study, records of all women with endometrial ablation at ages 30-49 years in Finland (1997-2014) were extracted from the Hospital Discharge Register and linked to the Cancer Registry and Finnish Central Population Register. The primary outcome was cancer incidences in the endometrial ablation cohort compared with those in the background population of the same age. Secondarily, the postablation hysterectomy rate was compared with that of a control cohort of similar-aged women extracted from the Finnish Central Population Register. Multivariate regression models with adjustment for age, parity, number of cesarean deliveries, history of sterilization, and the duration of follow-up were evaluated as risk factors for postablation hysterectomy. RESULTS: In total, 154 cancers (standardized incidence ratio [observed-to-expected ratio] 0.96, 95% CI 0.82-1.13) were diagnosed among 5,484 women treated with endometrial ablation during the follow-up of 39,892 women-years. The standardized incidence ratio for endometrial cancer was 0.56 (95% CI 0.12-1.64) and for breast cancer 0.86 (95% CI 0.67-1.09). A total of 1,086 (19.8%) women had postablation hysterectomy. Risk of hysterectomy was almost fourfold in the endometrial ablation cohort compared with 26,938 women in a control group (adjusted hazard ratio [HR] 3.63, 95% CI 3.32-3.96). Factors predisposing to postablation hysterectomy were leiomyomas (adjusted HR 1.78, 95% CI 1.03-3.10), age younger than 35 years (adjusted HR 1.44, 95% CI 1.15-1.81), at least two prior cesarean deliveries (adjusted HR 1.27, 95% CI 1.04-1.55), and history of sterilization (adjusted HR 1.15, 95% CI 1.01-1.32). CONCLUSION: Endometrial ablation was not associated with an elevated endometrial cancer or breast cancer risk in Finland. Leiomyomas, young age, and history of prior cesarean deliveries or sterilization were associated with an increased risk of postablation hysterectomy.

Impact of levonorgestrel-releasing intrauterine system use on the cancer risk of the ovary and fallopian tube.

BACKGROUND: Levonorgestrel-releasing intrauterine system (LNG-IUS) is used for contraception and heavy menstrual bleeding. A long-term hormone therapy can modify the risk of gynecologic cancers. Little is known about the impact of LNG-IUS use on the risk for invasive and borderline ovarian tumor subtypes or for primary fallopian tube carcinoma. We examined the associations of LNG-IUS use with these tumors. MATERIAL AND METHODS: We identified from the national Medical Reimbursement Registry of Finland the women aged 30-49 years who had used LNG-IUS for menorrhagia in 1994-2007, and from the Finnish Cancer Registry ovarian cancers and primary fallopian tube carcinomas diagnosed before the age of 55 and by the end of 2013. RESULTS: A total of 77 invasive ovarian cancers and seven primary fallopian tube carcinoma cases were diagnosed in a cohort of 93 843 LNG-IUS users during the follow-up of 1 083 126 women-years. The LNG-IUS users had decreased risk for both invasive ovarian cancer [standardized incidence ratio (SIR) 0.59, 95% confidence interval (CI) 0.47-0.73] and for borderline ovarian tumors (SIR 0.76, 95% CI 0.57-0.99) as compared to the background population. The risk of primary fallopian tube carcinoma was not increased (SIR 1.22, 95% CI 0.49-2.50). Decreased risks for mucinous (SIR 0.49, 95% CI 0.24-0.87), endometrioid (SIR 0.55, 95% CI 0.28-0.98), and serous ovarian carcinomas (SIR 0.75, 95% CI 0.55-0.99) were seen in LNG-IUS users. CONCLUSIONS: LNG-IUS use associated with decreased risk for both invasive and borderline ovarian tumors. The incidence of primary fallopian tube carcinoma did not significantly differ between LNG-IUS users and the background population.

Levonorgestrel-releasing intrauterine system and the risk of breast cancer: A nationwide cohort study.

BACKGROUND: Prolonged steroid hormone therapy increases the risk of breast cancer, especially the risk of lobular cancer, but the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) use is controversial. In this study we aimed to test the hypothesis that risk for lobular breast cancer is elevated among LNG-IUS users. MATERIAL AND METHODS: We identified from the national Medical Reimbursement Registry of Finland the women aged 30-49 who had used LNG-IUS for the treatment or prevention of menorrhagia in 1994-2007, and from the Finnish Cancer Registry breast cancers diagnosed before the age of 55 and by the end of 2012. RESULTS: A total of 2015 women had breast cancer diagnosed in a cohort of 93 843 LNG-IUS users during follow-up consisting of 1 032 767 women-years. The LNG-IUS users had an increased risk for both ductal breast cancer [standardized incidence ratio (SIR) 1.20, 95% confidence interval (CI) 1.14-1.25] and for lobular breast cancer (SIR 1.33, 95% CI 1.20-1.46), as compared with the general female population. The highest risk was found in LNG-IUS users who purchased the device at least twice, whose SIR for lobular cancer was 1.73 (95% CI 1.37-2.15). CONCLUSIONS: The results imply that intrauterine administration of levonorgestrel is not only related to an excess risk of lobular breast cancer but also, in contrary to previous assumptions, to an excess risk of ductal breast cancer.

Cancer risk in women using the levonorgestrel-releasing intrauterine system in Finland.

OBJECTIVE: To examine the association between premenopausal use of the levonorgestrel-releasing intrauterine system and cancer incidence in Finland with a special focus on endometrial adenocarcinoma. METHODS: All Finnish women aged 30-49 years using a levonorgestrel-releasing intrauterine system for treatment of menorrhagia in 1994-2007 (n=93,843) were identified from the National Reimbursement Registry and linked to the Finnish Cancer Registry data. The incidence of cancers in levonorgestrel-releasing intrauterine system users was compared with that in the general population. RESULTS: A total of 2,781 cancer cases were detected in levonorgestrel-releasing intrauterine system users during the follow-up of 855,324 women-years. The standardized incidence ratio (observed-to-expected ratio) for endometrial adenocarcinoma was 0.50 (95% confidence interval [CI] 0.35-0.70; 34 observed compared with 68 expected cases) after the first levonorgestrel-releasing intrauterine system purchase and 0.25 (95% CI 0.05-0.73; three observed compared with 12 expected cases) after two purchases. The standardized incidence ratio for ovarian cancer was 0.60 (95% CI 0.45-0.76; 59 observed compared with 99 expected cases), for pancreatic cancer 0.50 (95% CI 0.28-0.81; 15 observed compared with 30 expected cases), and for lung cancer 0.68 (95% CI 0.49-0.91; 43 observed compared with 63 expected cases). The standardized incidence ratio for breast cancer among all levonorgestrel-releasing intrauterine system users was 1.19 (95% CI 1.13-1.25; 1,542 observed compared with 1,292 expected cases). CONCLUSION: The levonorgestrel-releasing intrauterine system may have a protective effect against endometrial malignant transformation. Using the levonorgestrel-releasing intrauterine system for treatment of menorrhagia during reproductive years was associated with a lower incidence of endometrial, ovarian, pancreatic, and lung cancers than expected. Levonorgestrel-releasing intrauterine system use was associated with a higher than expected incidence of breast cancer. LEVEL OF EVIDENCE: II.

Smoking and sVEGFR-1: circulating maternal concentrations and placental expression.

Smoking reduces the expression of VEGFR-1 in non-pregnant women. In pregnant women it reduces the risk of pre-eclampsia, which in turn is associated with increased placental expression of VEGFR-1 and increased maternal circulating soluble VEGFR-1 (sVEGFR-1). We therefore hypothesized that smoking might affect VEGFR-1 expression in pregnant women. In maternal plasma sVEGFR-1 concentrations during the third trimester in both smoking (median 1088, range 834-1362ng/L, n=20) and non-smoking (728, 719-1336ng/L, n=19) women were higher than during the second trimester (smokers 374, 291-683ng/L, n=6, p>0.05; non-smokers 375, 290-667ng/L, n=22, p<0.001). No difference was observed between smokers and non-smokers. Secretion of sVEGFR-1 into the culture medium, as well as the pattern and intensity of immunostaining in first trimester placenta were similar in tissue from smoking (n=22) and non-smoking (n=20) women. Thus, contrary to our hypothesis, smoking does not affect circulating maternal sVEGFR-1 concentrations or placental secretion of sVEGFR-1 or expression of VEGFR-1 in vitro.

Monoclonal antibodies, immunofluorometric assay, and detection of human semenogelin in male reproductive tract: no association with in vitro fertilizing capacity of sperm.

Semenogelin plays an important role in sperm clotting and is degraded into smaller fragments by prostate-specific antigen (PSA) during clot liquefaction. Semenogelin and its fragments inhibit sperm motility in vitro. We studied the expression of semenogelin I mRNA and its localization in various tissues of the male genital tract. We also studied semenogelin concentrations with respect to sperm parameters and the outcome of in vitro fertilization. Semenogelin protein was detected by immunohistochemical staining and semenogelin I mRNA was detected by Northern blot analysis in the seminal vesicles and ampullary part of the vas deferens, whereas specimens from the prostate, epididymis, testis, and the female genital tract were negative. Using monoclonal antibodies against semenogelin, an immunofluorometric assay was developed to measure semenogelin levels in seminal plasma and to evaluate possible correlations with sperm parameters and fertilization in vitro. No correlation was found between the semenogelin concentration and the volume of the ejaculate, sperm concentration, sperm motility, or in vitro fertilization rate. Semenogelin levels were positively correlated with the total protein concentration in seminal plasma, and there was an inverse correlation between the concentration of semenogelin and that of PSA. The levels of semenogelin appear to bear no relationship to the in vitro fertilization capacity of the spermatozoa.