IMPLICACIONES DE LA OOFORECTOMÍA PROFILÁCTICA Y EL USO DE TRH SOBRE LA MORTALIDAD FEMENINA XIII

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IMPLICACIONES DE LA OOFORECTOMÍA PROFILÁCTICA Y EL USO DE TRH SOBRE LA MORTALIDAD FEMENINA XIII Congreso Costarricense de Climaterio Menopausia y osteoporosis 2014 Dr. Leonardo Orozco S. Colaboración Cochrane Iberoamericana

OOFORECTOMÍA PROFILÁCTICA Significado Entender que el termino OP implica que los ovarios son normales al tiempo de la escisión quirúrgica. Se realiza por posibles beneficios futuros Datos del Centro de Prevención y Control de Enfermedades en Estados Unidos 1988 a 1993, revelan que la preservación ovárica ocurre solamente en un 40% -50% de las pacientes a quienes se les efectúa histerectomía a los 40 ó más años de edad. Cifras conservadoras sugieren que a 300 000 mujeres se les hace una ooforectomía bilateral profiláctica cada año.

OOFORECTOMÍA PROFILÁCTICA Costa Rica Según la base de datos de egreso hospitalario del Hospital de las Mujeres en San José Costa Rica, se efectúo una ooforectomía bilateral en el 71% de las pacientes de histerectomía entre los años 2003 y 2005 Referencias Lepine LA, Hillis SD, Marchbanks PA, Koonin LM, Morrow B, Kieke BA, et al. Hysterectomy surveillance-united States, 1980-1993. MMWR 1997; 46: S 4:1-15. Parker WH, Broder MS, Liu Z, Shoupe D, Farquhar C, Berek JS. Ovarian conservation at the time of hysterectomy for benign disease. Obstet Gynecol 2005; 106: 219-226. AMC, vol 50 (3), julio-septiembre 2008.

Rate of bilateral oophorectomy stratified by age in women having hysterectomy for benign disease from 2000 to 2010 Based on retrospective cohort study 752,045 women aged 40-64 years with hysterectomy for benign disease from 2000 to 2010 evaluated 46.4% had bilateral oophorectomy Rate of bilateral oophorectomy by age < 40 years 25.7% 40-44 years 37.3% 45-49 years 59.2% 50-54 years 74.8% 55-59 years 74.5% 60-64 years 69% Rate of bilateral oophorectomy decreased with more recent year of surgery for all age groups CONCLUSION: The rate of ovarian conservation is increasing, particularly among women younger than 50 years old. Reference - Obstet Gynecol 2013 Apr;121(4):717, editorial can be found in Obstet Gynecol 2013 Apr;121(4): 701

American College of Obstetricians and Gynecologists (ACOG) recommendations for elective and risk-reducing salpingooophorectomy Factors supporting oophorectomy genetic risk for ovarian cancer based on family history or genetic testing including BRCA mutations or family history of hereditary non polyposis colorectal cancer presence of bilateral ovarian neoplasms severe endometriosis pelvic inflammatory disease or tuboovarian abscesses postmenopausal state? Factors supporting ovarian preservation premenopausal state preservation of fertility impact on sexual function, libido, and quality of life in young women presence of risk factors for osteoporosis in premenopausal women Reference - American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin 89 Obstet Gynecol 2008 Jan;111(1):231, reaffirmed 2013 Jan or at National Guideline Clearinghouse 2008 Jun 16:12190)

Insufficient evidence to evaluate benefit of hysterectomy plus oophorectomy vs. hysterectomy alone in premenopausal women with benign gynecologic conditions Based on Cochrane review Systematic review of randomized and controlled clinical trials evaluating hysterectomy plus oophorectomy vs. hysterectomy alone in premenopausal women with benign gynecologic conditions Only 1 controlled trial with 362 women included Primary outcomes of mortality or future gynecologic surgical interventions not reported Possible benefit on psychological well-being for both treatment groups at 1 year follow-up, but no differences between groups No randomized trials identified Reference - Cochrane Database Syst Rev 2008 Apr 16;(3):CD005638

CARPOMW: Central American Research on Prophylactic Ovariectomy amongst Menopausal Women A clinical trial of bilateral prophylactic ovariectomy versus conservation of the ovaries amongst menopausal participants that will undergo an elective hysterectomy Authors: Background What is a Prophylactic Ovariectomy? A prophylactic ovariectomy implies that the ovaries are normal at the time of the surgery and that it is performed for a future protective benefit. Current medical practice supports 45 years as the age at which a prophylactic ovariectomy should be strongly recommended. Current Practices The predominant teaching is that prophylactic ovariectomy in participants with low risk of ovarian cancer must be avoided in women under 40 years old, routinely performed in women over 50 years old, and is individualized in between. However, despite the fact that this is a widespread practice, current scientific evidence supporting prophylactic ovariectomy is weak, and is the result of research amongst pre-menopausal women. The debate regarding short- and long-term effects of prophylactic ovariectomy remains unresolved. The decision to perform this intervention is based more on opinion than on methodologically high quality studies. Rationale This prospective, randomized, and multi-centre controlled study attempts to evaluate the short- and long-term effects that prophylactic ovariectomy has on the quality of life and sexual well-being of the post-menopausal woman. Objectives To establish the extent to which prophylactic ovarietomy affects patient-reported outcomes associated with overall well-being and healthrelated quality of life amongst post-menopausal women. Design A prospective, randomized, multicentre controlled study. This study will be carried out in hospitals in Costa Rica, El Salvador, Panama, and Uruguay. Research Flowchart Participants that undergo a hysterectomy are eligible if: 1. They are between 45 and 65 years old. 2. They will undergo an elective hysterectomy for a benign cause. 3. Woman has provided written informed consent to participate in the study Hysterectom y and Prophylactic Ovariectomy Monitoring (2 yrs) Complete Monitoring (5 yrs) Informed Consent Randomization 1st Publication 2nd Publication Hysterectomy (without Prophylactic Ovariectomy) Monitoring (2 yrs) Complete Monitoring (5 yrs) Study Characteristics Inclusion Criteria 1 Women about to have an elective hysterectomy for benign causes shall be considered. 2. Woman has provided written informed consent to participate in the study. 3. Woman has or is not had a menstrual period for 12 months or more Exclusion Criteria 1. The woman is currently participating or has participated in an investigational trial during the previous four months 2. The woman in the judgment of the principal investigator, is unlikely to be able to be prospectively followed for a five year period 3. The woman has a previous family history of first grade ovarian cancer 4. The woman has antecedents of psychiatric disease and the use of psychotropic drugs. 5. The woman requires a hysterectomy due to the presence of neoplasia. Endpoints physical health, psychological health, family environment, sexual relationships, social support requirement, requirement for further pelvic surgical intervention. Acknowledgements We are grateful for the help of the Cochrane Menstrual Disorders and Subfertility Group, especially for the support of Jane Clark, Review Group Coordinator.

Bilateral oophorectomy associated with decreased risk of breast and ovarian cancer but increased risk of all-cause mortality Based on prospective cohort of 29,380 female participants in Nurses' Health Study who underwent hysterectomy for benign disease 24 year follow-up Bilateral oophorectomy associated with increased total mortality fatal and nonfatal coronary heart disease lung cancer total cancer mortality For those never having used estrogen therapy, bilateral oophorectomy before age 50 years was associated with an increased risk of all-cause mortality, CHD, and stroke Bilateral oophorectomy associated with decreased breast cancer ovarian cancer all cancers Reference - Obstet Gynecol 2009 May;113(5):1027

BILATERAL OPHORECTOMY VS OVARIAN CONSERVATION 1.12 (95% [CI] 1.03-1.21) for total mortality 1.17 (95% CI 1.02-1.35) for fatal plus non fatal CHD Lung cancer incidence (HR=1.26, 95% CI 1.02-1.56, number needed to harm=190) Total cancer mortality (HR=1.17, 95% CI 1.04-1.32) Reference - Obstet Gynecol 2009 May;113(5):1027

BILATERAL OPHORECTOMY VS OVARIAN CONSERVATION Breast cancer (HR 0.75, 95% CI 0.68-0.84) Ovarian cancer (HR 0.04, 95% CI 0.01-0.09, number needed to treat=220) Total cancers (HR 0.90, 95% CI 0.84-0.96) Risk of dying of other cancers exceeded the risk of dying from ovarian cancer (low incidence) and breast cancer (high longterm survival rate).

Bilateral oophorectomy may increase risk of all-cause mortality, particularly in never-users of estrogen therapy with hysterectomy for benign disease before age 50 years Based on cohort study of 30,117 female participants in Nurses' Health Study who underwent hysterectomy for benign disease 28-year follow-up Bilateral oophorectomy associated with increased risk of all-cause mortality (hazard ratio [HR] 1.13, 95% CI 1.06-1.21) All-cause mortality in women < 50 years old at time of hysterectomy who never used estrogen therapy (HR 1.41, 95% CI 1.04-1.92) assuming a 35-year lifespan after oophorectomy: number needed to harm for all-cause death=8, coronary heart disease death=33, and lung cancer death=50 Reference - Obstet Gynecol 2013 Apr;121(4):709, editorial can be found in Obstet Gynecol 2013 Apr;121(4):701

Insufficient evidence to suggest bilateral oophorectomy is associated with risk of coronary heart disease Based on systematic review limited by heterogeneity Systematic review of 7 observational studies (including 3 large prospective cohorts) evaluating association between bilateral oophorectomy and risk of coronary heart disease 4 studies found increased risk in sub-groups 3 limited studies found no increased risk heterogeneity of trials did not allow meta-analysis Reference - Am J Obstet Gynecol 2009 Feb;200(2):140e1

Based on cohort of 25,448 postmenopausal women without family history of ovarian cancer from Women's Health Initiative Observational Study 56% had hysterectomy with oophorectomy 44% had hysterectomy with ovary conservation 78% were current or past users of estrogen and/or progestin mean follow-up 7.6 years incidence of ovarian cancer 0.02% in women with oophorectomy vs. 0.33% in women without oophorectomy (p < 0.05, NNT 323) no significant differences in total cancer, breast cancer, colorectal cancer or lung cancer, all-cause mortality, cardiovascular disease, cardiovascular surgery, stroke, hip fracture. oophorectomy associated with trend toward reduced risk of breast cancer in subgroup of women who had hysterectomy at < 40 years old (hazard ratio 0.72, 95% CI 0.51-1.02) CONCLUSIONS: In this large prospective cohort study, BSO decreased the risk of ovarian cancer compared with hysterectomy and ovarian conservation, but incident ovarian cancer was rare in both groups. Our findings suggest that BSO may not have an adverse effect on cardiovascular health, hip fracture, cancer, or total mortality compared with hysterectomy and ovarian conservation. Reference - Arch Intern Med 2011 Apr 25;171(8):760

Long-term incidence of oophorectomy appears similar in women with hysterectomy for benign indications compared to women without hysterectomy Based on cohort study 4,931 women with ovary-sparing hysterectomy for benign indications from 1965 to 2002 compared with 4,931 similar women without hysterectomy median follow-up 19.6 years for women with hysterectomy and 19.4 years for women without hysterectomy comparing women with vs. without hysterectomy, cumulative incidence of oophorectomy: 3.5% vs. 1.9% at 10 years after hysterectomy (not significant) 6.2% vs. 4.8% at 20 years after hysterectomy (not significant) 9.2% vs. 7.3% at 30 years after hysterectomy (not significant) Reference - Obstet Gynecol 2013 May;121(5):1069

Gracias