Endometrial cancer associated with various forms of postmenopausal hormone therapy: a case control study.
ABSTRACT This study evaluates the effect of different modes of estradiol-progestagen therapy (EPT) regimens on the postmenopausal endometrial cancer risk in Finland. Women diagnosed with endometrial cancer in 1995-2007 at the age of 50-80 years were identified from the Finnish Cancer Registry (N = 7,261). For each case, three age-matched controls were retrieved from the Finnish Population Register. The use of EPT since 1994 was ascertained from the national Medical Reimbursement Register. Odds ratios (ORs) for different EPT regimens were calculated with conditional logistic regression analysis, adjusted for parity and ages at the deliveries. For use of <5 years, the OR for sequential EPT was 0.67 (95% confidence interval 0.52-0.86), for continuous EPT 0.45 (0.27-0.73), and for estradiol plus levonorgestrel-releasing intrauterine device system (LNG-IUS) 0.39 (0.17-0.88). A decreased risk persisted for the use of continuous EPT and estradiol plus LNG-IUS of up to 10 years. The use of long-cycle EPT showed a tendency toward an elevated risk both for exposure of <5 years (1.40; 0.82-2.38) and for estimated use of >5 years (1.63; 1.12-2.38). For an estimated exposure of >10 years, the risk for endometrial cancer was elevated for both users of long-cycle EPT (2.95; 2.40-3.62) and sequential EPT (1.38; 1.15-1.66). Norethisterone acetate and medroxyprogesterone acetate as parts of EPT did not differ in their endometrial cancer risk. The use of tibolone showed no endometrial risk. The use of sequential and long-cycle EPT is associated with an increased risk of endometrial cancer, whereas the use of continuous EPT or estradiol plus LNG-IUS shows a decreased risk.
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ABSTRACT: Postmenopausal uterine bleeding is defined as uterine bleeding after permanent cessation of menstruation resulting from loss of ovarian follicular activity. Bleeding can be spontaneous or related to ovarian hormone replacement therapy or to use of selective estrogen receptor modulators (eg, tamoxifen adjuvant therapy for breast carcinoma). Because anovulatory "cycles" with episodes of multimonth amenorrhea frequently precede menopause, no consensus exists regarding the appropriate interval of amenorrhea before an episode of bleeding that allows for the definition of postmenopausal bleeding. The clinician faces the possibility that an underlying malignancy exists, knowing that most often the bleeding comes from a benign source. Formerly, the gold-standard clinical investigation of postmenopausal uterine bleeding was institution-based dilation and curettage, but there now exist office-based methods for the evaluation of women with this complaint. Strategies designed to implement these diagnostic methods must be applied in a balanced way considering the resource utilization issues of overinvestigation and the risk of missing a malignancy with underinvestigation. Consequently, guidelines and recommendations were developed to consider these issues and the diverse spectrum of practitioners who evaluate women with postmenopausal bleeding. The guideline development group determined that, for initial management of spontaneous postmenopausal bleeding, primary assessment may be with either endometrial sampling or transvaginal ultrasonography, allowing patients with an endometrial echo complex thickness of 4 mm or less to be managed expectantly. Guidelines are also provided for patients receiving selective estrogen receptor modulators or hormone replacement therapy, and for an endometrial echo complex with findings consistent with fluid in the endometrial cavity.The Permanente journal 12/2013;
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ABSTRACT: To determine cancer incidence among Finnish women with 10 or more deliveries. Finnish women with at least 10 childbirths before December 31, 2010 (n=4,967) were identified from the Finnish Population Register and followed for cancer incidence through the Finnish Cancer Registry to the end of 2010. Cancer risks in this cohort were expressed as ratios between observed and expected numbers of cases (standardized incidence ratios), both drawn from the Finnish Cancer Registry, with 95% confidence intervals (CIs). Total cancer incidence was markedly lower than in the reference population (656 cases, standardized incidence ratio 0.76, 95% CI 0.73-0.79). There was clearly less breast (0.44, 0.35-0.53), ovarian (0.49, 0.28-0.80), endometrial (0.31, 0.17-0.44), and basal cell skin cancer (0.72, 0.60-0.85) than in the reference population. The incidence of thyroid cancer (2.33, 1.59-3.29), lip cancer (2.87, 1.05-6.24), and uterine sarcoma (3.41, 1.47-6.72) was markedly increased. Women with 10 or more deliveries show a decreased overall cancer incidence as a result of decreased risks of cancers of the ovary, endometrium, and breast and basal cell carcinoma of the skin. The increased risks were observed in thyroid cancer and some rare cancer types. LEVEL OF EVIDENCE:: II.Obstetrics and Gynecology 04/2014; 123(4):811-816. · 4.80 Impact Factor
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ABSTRACT: ABSTRACT Hormone replacement therapy (HRT) remains the gold standard for treatment of climacteric symptoms in menopausal women; it is relatively safe in healthy subjects for at least 5 years, provided it had been initiated before the age of 60 years and/or within 10 years from menopause. Estrogen probably adds some cardioprotection, that can, however, be obscured by progestogens, especially medroxyprogesterone acetate (MPA). Oral HRT is associated with an increased risk of venous thromboembolism (VTE), gallbladder disease and possibly stroke. The increased occurrence of all these events can be prevented by the use of the transdermal route of estradiol administration; this route seems also advantageous for women with diabetes, hypertension and other cardiovascular risk factors, and also especially with advancing age. Endometrial protection by any progestogen is insufficient in the mid to long term when cyclical, sequential regimens are used; full protection can be secured only by continuous combined estrogen + progestogen. Natural, 'body-identical' progesterone, devoid of any androgenic as well as glucocorticoid activities but being slightly hypotensive due to its antimineralocorticoid activity, appears to be the optimal progestogen in terms of cardiovascular effects, blood pressure, VTE, probably stroke and even breast cancer (contrary to synthetic progestogens and particularly MPA, which appear to be mitogenic on breast cells, in synergism with estrogen). HRT optimization can thus be achieved by combining low doses of estrogen given transdermally with micronized oral progesterone; such optimized HRT will allow us to treat symptomatic women for as long as required. Asymptomatic women at risk of (osteoporotic) fractures can also be treated with this optimized HRT as long as their individual risk/benefit ratio remains favorable (thanks to the absence of increased risks of VTE, stroke and breast cancer).Climacteric 08/2013; 16 Suppl 1:44-53. · 1.96 Impact Factor