Female Reproductive and Gynecologic Considerations in Chronic Kidney Disease: Adolescence and Young Adulthood
2021; Elsevier BV; Volume: 7; Issue: 2 Linguagem: Inglês
10.1016/j.ekir.2021.11.003
ISSN2468-0249
AutoresDanica H. Chang, Sandra M. Dumanski, Sofia B. Ahmed,
Tópico(s)Reproductive System and Pregnancy
ResumoChronic kidney disease (CKD) increasingly affects younger people, including adolescents and young adults. CKD among females is accompanied by unique reproductive and gynecologic health concerns; though to date, this area has not been well studied. Hormonal disruptions attributed to CKD may underlie the high prevalence of abnormal uterine bleeding and influence the age of menarche in adolescents. Period poverty as a socioeconomic barrier further exacerbates the female-specific burdens of CKD. Reduced fertility in CKD is likely multifactorial and may be related to a reduction in ovarian reserve, reproductive hormone disturbances, and gonadotoxic medication use in addition to low sexual function and activity. Fertility, sexual function and activity, and risk of sexually transmitted infections increase with transplantation. Pregnancy is possible at any stage of CKD, although often accompanied by high risks of maternal and fetal complications. Contraception is thus an important consideration in CKD, but use is low and the risks and benefits of different forms in the setting of CKD are not well characterized. Though patients with CKD report reproductive health as an important element of care, many nephrologists report lack of confidence and training in this area, highlighting the need for targeted research and education. The unique reproductive health care needs of the growing transgender youth population warrant attention in nephrology training with multidisciplinary input. This review will discuss female reproductive health and gynecologic considerations in adolescents and young adults with CKD while proposing clinical and research strategies to improve this understudied yet important aspect of kidney care. Chronic kidney disease (CKD) increasingly affects younger people, including adolescents and young adults. CKD among females is accompanied by unique reproductive and gynecologic health concerns; though to date, this area has not been well studied. Hormonal disruptions attributed to CKD may underlie the high prevalence of abnormal uterine bleeding and influence the age of menarche in adolescents. Period poverty as a socioeconomic barrier further exacerbates the female-specific burdens of CKD. Reduced fertility in CKD is likely multifactorial and may be related to a reduction in ovarian reserve, reproductive hormone disturbances, and gonadotoxic medication use in addition to low sexual function and activity. Fertility, sexual function and activity, and risk of sexually transmitted infections increase with transplantation. Pregnancy is possible at any stage of CKD, although often accompanied by high risks of maternal and fetal complications. Contraception is thus an important consideration in CKD, but use is low and the risks and benefits of different forms in the setting of CKD are not well characterized. Though patients with CKD report reproductive health as an important element of care, many nephrologists report lack of confidence and training in this area, highlighting the need for targeted research and education. The unique reproductive health care needs of the growing transgender youth population warrant attention in nephrology training with multidisciplinary input. This review will discuss female reproductive health and gynecologic considerations in adolescents and young adults with CKD while proposing clinical and research strategies to improve this understudied yet important aspect of kidney care. The prevalence of CKD in children is steadily increasing, with a higher incidence of kidney replacement therapy in adolescents compared with other age groups worldwide.1Kaspar C.D.W. Bholah R. Bunchman T.E. A review of pediatric chronic kidney disease.Blood Purif. 2016; 41: 211-217https://doi.org/10.1159/000441737Crossref PubMed Scopus (39) Google Scholar Although the most common causes of kidney disease at a global level are hypertension and diabetes,2Jha V. Garcia-Garcia G. Iseki K. et al.Chronic kidney disease: global dimension and perspectives.Lancet. 2013; 382: 260-272https://doi.org/10.1016/s0140-6736(13)60687-xAbstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar,3National Institute of Health, National Institute of Diabetes and Digestive and Kidney DiseasesKidney disease statistics for the United States. National Institute of Health—National Institute of Diabetes and Digestive and Kidney Diseases.https://www.niddk.nih.gov/health-information/health-statistics/kidney-diseaseGoogle Scholar childhood onset of kidney disease is most frequently due to congenital abnormalities and hereditary disorders.4North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) 2008 annual report. NAPRTCS. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/viewer.html?pdfurl=https%3A%2F%2Fwww.naprtcs.org%2Fsystem%2Ffiles%2F2008_Annual_CKD_Report.pdf&clen=2915899. Accessed February 24, 2021.Google Scholar, 5Ardissino G. Dacco V. Testa S. et al.Epidemiology of chronic renal failure in children: data from the ItalKid project.Pediatrics. 2003; 111: e382-e387https://doi.org/10.1542/peds.111.4.e382Crossref PubMed Scopus (377) Google Scholar, 6Mong Hiep T.T. Ismaili K. Collart F. et al.Clinical characteristics and outcomes of children with stage 3–5 chronic kidney disease.Pediatr Nephrol. 2010; 25: 935-940https://doi.org/10.1007/s00467-009-1424-2Crossref PubMed Scopus (55) Google Scholar, 7Ingelfinger J.R. Kalantar-Zadeh K. Schaefer F. World Kidney Day Steering CommitteeAverting the legacy of kidney disease—focus on childhood.Kidney Dis. 2016; 2: 46-52https://doi.org/10.1159/000443819Crossref Google Scholar The reduced rate of congenital abnormalities of the kidney and urinary tract among females may help to explain the lower incidence of CKD compared with males in the adolescent population.8Harambat J. Van Stralen K.J. Kim J.J. Tizard E.J. Epidemiology of chronic kidney disease in children.Pediatr Nephrol. 2012; 27: 363-373https://doi.org/10.1007/s00467-011-1939-1Crossref PubMed Scopus (487) Google Scholar Furthermore, compared with the adult population, glomerulonephritides are a more common cause of CKD in children, particularly in the adolescent population after puberty.4North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) 2008 annual report. NAPRTCS. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/viewer.html?pdfurl=https%3A%2F%2Fwww.naprtcs.org%2Fsystem%2Ffiles%2F2008_Annual_CKD_Report.pdf&clen=2915899. Accessed February 24, 2021.Google Scholar,8Harambat J. Van Stralen K.J. Kim J.J. Tizard E.J. Epidemiology of chronic kidney disease in children.Pediatr Nephrol. 2012; 27: 363-373https://doi.org/10.1007/s00467-011-1939-1Crossref PubMed Scopus (487) Google ScholarCKD in the female population is often accompanied by abnormal uterine bleeding, sexual dysfunction, reduced fertility, and higher risk pregnancies.9Dumanski S.M. Ahmed S.B. Fertility and reproductive care in chronic kidney disease.J Nephrol. 2019; 32: 39-50https://doi.org/10.1007/s40620-018-00569-9Crossref PubMed Scopus (10) Google Scholar,10Wiles K.S. Nelson-Piercy C. Bramham K. Reproductive health and pregnancy in women with chronic kidney disease.Nat Rev Nephrol. 2018; 14: 165-184https://doi.org/10.1038/nrneph.2017.187Crossref PubMed Scopus (42) Google Scholar Commonly used immunosuppressive medications (e.g., cyclophosphamide, mycophenolate mofetil) for autoimmune glomerular disorders, which disproportionately affect females, have important implications for uterine bleeding, fertility, and the potential for fetal malformations.11Leroy C. Rigot J.-M. Leroy M. et al.Immunosuppressive drugs and fertility.Orphanet J Rare Dis. 2015; 10: 136https://doi.org/10.1186/s13023-015-0332-8Crossref PubMed Scopus (93) Google Scholar According to the North American Pediatric Renal Trials and Collaborative Studies database, adolescents represent the largest group of pediatric kidney transplant recipients.12Shapiro R. Sarwal M.M. Pediatric kidney transplantation.Pediatr Clin North Am. 2010; 57: 393-400https://doi.org/10.1016/j.pcl.2010.01.016Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Although CKD is associated with increased abnormal uterine bleeding,13Lim V.S. Henriquez C. Sievertsen G. Frohman L.A. Ovarian function in chronic renal failure: evidence suggesting hypothalamic anovulation.Ann Intern Med. 1980; 93: 22-27Crossref Scopus (170) Google Scholar, 14Holley J.L. Schmidt R.J. Bender F.H. et al.Gynecologic and reproductive issues in women on dialysis.Am J Kidney Dis. 1997; 29: 685-690https://doi.org/10.1016/s0272-6386(97)90120-7Abstract Full Text PDF PubMed Google Scholar, 15Chakhtoura Z. Meunier M. Caby J. et al.Gynecologic follow up of 129 women on dialysis and after kidney transplantation: a retrospective cohort study.Eur J Obstet Gynecol Reprod Biol. 2015; 187: 1-5https://doi.org/10.1016/j.ejogrb.2015.01.004Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar kidney transplantation, at least in the adult population, may restore uterine bleeding.15Chakhtoura Z. Meunier M. Caby J. et al.Gynecologic follow up of 129 women on dialysis and after kidney transplantation: a retrospective cohort study.Eur J Obstet Gynecol Reprod Biol. 2015; 187: 1-5https://doi.org/10.1016/j.ejogrb.2015.01.004Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar,16Filocamo M.T. Zanazzi M. Li Marzi V. et al.Sexual dysfunction in women during dialysis and after renal transplantation.J Sex Med. 2009; 6: 3125-3131https://doi.org/10.1111/j.1743-6109.2009.01400.xAbstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar Kidney transplantation guidelines17Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work GroupKDIGO clinical practice guideline for the care of kidney transplant recipients.Am J Transplant. 2009; 9: S1-S155https://doi.org/10.1111/j.1600-6143.2009.02834.xCrossref PubMed Scopus (12) Google Scholar,18EBPG Expert Group on Renal TransplantationEuropean best practice guidelines for renal transplantation. Section IV: long-term management of the transplant recipient. IV.10. Pregnancy in renal transplant recipients.Nephrol Dial Transplant. 2002; 17: 50-55Google Scholar discourage pregnancy in females for the first year post-transplant owing to risk of allograft rejection and pregnancy complications. Finally, pregnancy itself can have a detrimental and permanent impact on kidney function.19Piccoli G.B. Cabiddu G. Attini R. et al.Risk of adverse pregnancy outcomes in women with CKD.J Am Soc Nephrol. 2015; 26: 2011-2022https://doi.org/10.1681/asn.2014050459Crossref PubMed Scopus (0) Google Scholar,20Hladunewich M.A. Melamed N. Bramham K. Pregnancy across the spectrum of chronic kidney disease.Kidney Int. 2016; 89: 995-1007https://doi.org/10.1016/j.kint.2015.12.050Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar Taken together, these multiple factors underscore the critical value of providing reproductive care to all females living with CKD, including adolescents who require individualized care during this phase of physiological and social transition. This narrative review will broadly summarize female reproductive and gynecologic considerations in the care of the adolescent and young adult populations with CKD.MethodsFor the purpose of providing a summary on female reproductive and gynecologic health among adolescents with CKD, the first author (DHC) searched 2 electronic sources, MEDLINE and Google Scholar. The terms “reproductive health” or “gynecology” in combination with “chronic kidney disease,” “chronic renal insufficiency,” “end-stage kidney disease,” “chronic renal failure,” “dialysis,” “transplant,” and “nephrology” and other related terms helped identify relevant literature. The terms “contraception,” “menstruation,” “sexual dysfunction,” and “adolescent” in combination with the same Medical Subject Headings were also searched in MEDLINE. These searches were completed by May 2021. Reference lists from relevant articles were hand-searched, and the search was further supplemented by key articles from nephrologists with expertise in women’s health (SBA and SMD). Priority for inclusion in this review was given to original articles reporting original data (i.e., observational studies as randomized control trials were lacking), clinical practice guidelines, and systematic reviews.Kidney Disease and the Menstrual CycleThe menstrual cycle encompasses the time between the first day of uterine bleeding to the next first day of uterine bleeding,21Welt C.K. Physiology of the normal menstrual cycle.https://www.uptodate.com/contents/physiology-of-the-normal-menstrual-cycle?search=menstrual%20cycle&source=search_result&selectedTitle=1∼150&usage_type=default&display_rank=1Google Scholar and a healthy menstrual cycle lasts 24 to 38 days with bleeding occurring for ≤8 days (on average, 5 days).22Hoffman B.L. Schorge J.O. Halvorson L.M. et al.Chapter 8: abnormal uterine bleeding.in: Williams Gynecology. 4th ed. McGraw-Hill Education LLC, 2020Google Scholar Details regarding the healthy menstrual cycle are outlined elsewhere.21Welt C.K. Physiology of the normal menstrual cycle.https://www.uptodate.com/contents/physiology-of-the-normal-menstrual-cycle?search=menstrual%20cycle&source=search_result&selectedTitle=1∼150&usage_type=default&display_rank=1Google Scholar,23The Society of Obstetricians and Gynaecologists of CanadaNormal periods—menstrual cycle basics. The Society of Obstetricians and Gynaecologists of Canada.https://www.yourperiod.ca/normal-periods/menstrual-cycle-basics/Google ScholarIn CKD, disruption of the hypothalamic-pituitary-ovarian axis results in an abnormal reproductive hormone profile, where the degree of disruption increases with CKD progression (Figure 1).13Lim V.S. Henriquez C. Sievertsen G. Frohman L.A. Ovarian function in chronic renal failure: evidence suggesting hypothalamic anovulation.Ann Intern Med. 1980; 93: 22-27Crossref Scopus (170) Google Scholar,14Holley J.L. Schmidt R.J. Bender F.H. et al.Gynecologic and reproductive issues in women on dialysis.Am J Kidney Dis. 1997; 29: 685-690https://doi.org/10.1016/s0272-6386(97)90120-7Abstract Full Text PDF PubMed Google Scholar,24Cochrane R. Regan L. Undetected gynaecological disorders in women with renal disease.Hum Reprod. 1997; 12: 667-670https://doi.org/10.1093/humrep/12.4.667Crossref PubMed Scopus (47) Google Scholar As such, those with kidney failure are believed to have the most severe hormonal disruptions, and most studies have been conducted in this population.13Lim V.S. Henriquez C. Sievertsen G. Frohman L.A. Ovarian function in chronic renal failure: evidence suggesting hypothalamic anovulation.Ann Intern Med. 1980; 93: 22-27Crossref Scopus (170) Google Scholar,24Cochrane R. Regan L. Undetected gynaecological disorders in women with renal disease.Hum Reprod. 1997; 12: 667-670https://doi.org/10.1093/humrep/12.4.667Crossref PubMed Scopus (47) Google Scholar In kidney failure, the pulsatile release of gonadotropin-releasing hormone is impaired, resulting in a lack of follicle-stimulating hormone and luteinizing hormone cyclicity.13Lim V.S. Henriquez C. Sievertsen G. Frohman L.A. Ovarian function in chronic renal failure: evidence suggesting hypothalamic anovulation.Ann Intern Med. 1980; 93: 22-27Crossref Scopus (170) Google Scholar Consequently, estradiol levels stay relatively low, inhibiting the surge and ovulation of the luteinizing hormone. Elevated prolactin levels owing to reduced clearance and increased production also contribute to anovulation.13Lim V.S. Henriquez C. Sievertsen G. Frohman L.A. Ovarian function in chronic renal failure: evidence suggesting hypothalamic anovulation.Ann Intern Med. 1980; 93: 22-27Crossref Scopus (170) Google Scholar,24Cochrane R. Regan L. Undetected gynaecological disorders in women with renal disease.Hum Reprod. 1997; 12: 667-670https://doi.org/10.1093/humrep/12.4.667Crossref PubMed Scopus (47) Google Scholar,25Sievertsen G.D. Lim V.S. Nakawatase C. Frohman L.A. Metabolic clearance and secretion rates of human prolactin in normal subjects and in patients with chronic renal failure.J Clin Endocrinol Metab. 1980; 50: 846-852Crossref PubMed Google Scholar A possible mechanism of hormonal abnormalities in kidney failure is that high prolactin levels negatively feed back into the hypothalamic-pituitary-ovarian axis and inhibit gonadotropin-releasing hormone secretion, thus preventing gonadotropin release and resulting in abnormal uterine bleeding.26Ahmed S.B. Ramesh S. Sex hormones in women with kidney disease.Nephrol Dial Transplant. 2016; 31: 1787-1795https://doi.org/10.1093/ndt/gfw084Crossref PubMed Scopus (39) Google Scholar, 27Ginsburg E.S. Owen W.F. Reproductive endocrinology and pregnancy in women on hemodialysis.Semin Dial. 2007; 6: 105-116https://doi.org/10.1111/j.1525-139x.1993.tb00273.xCrossref Google Scholar, 28Palmer B.F. Clegg D.J. Gonadal dysfunction in chronic kidney disease.Rev Endocr Metab Disord. 2017; 18: 117-130https://doi.org/10.1007/s11154-016-9385-9Crossref PubMed Scopus (36) Google Scholar In a prospective study of 57 female adolescents with stage 4 CKD and kidney failure treated with hemodialysis and peritoneal dialysis, 49% had hyperprolactinemia.29Serret-Montaya J. Zurita-Cruz J.N. Villasís-Keever M.A. et al.Hyperprolactinemia as a prognostic factor for menstrual disorders in female adolescents with advanced chronic kidney disease.Pediatr Nephrol. 2020; 35: 1041-1049https://doi.org/10.1007/s00467-020-04494-7Crossref PubMed Scopus (1) Google Scholar When comparing participants with and without menstrual disturbances, prolactin levels were higher in those with menstrual disturbances.29Serret-Montaya J. Zurita-Cruz J.N. Villasís-Keever M.A. et al.Hyperprolactinemia as a prognostic factor for menstrual disorders in female adolescents with advanced chronic kidney disease.Pediatr Nephrol. 2020; 35: 1041-1049https://doi.org/10.1007/s00467-020-04494-7Crossref PubMed Scopus (1) Google ScholarKidney Disease and Age of MenarcheMenarche is the first occurrence of uterine bleeding and the beginning of the female reproductive lifespan. Among healthy adolescents, the median age of menarche is approximately 12 to 13 years.30Chumlea W.C. Schubert C.M. Roche A.F. et al.Age at menarche and racial comparisons in US girls.Pediatrics. 2003; 111: 110-113https://doi.org/10.1542/peds.111.1.110Crossref PubMed Scopus (488) Google Scholar,31Diaz A. Laufer M.R. Breech L.L. et al.Menstruation in girls and adolescents: using the menstrual cycle as a vital sign.Pediatrics. 2006; 118: 2245-2250https://doi.org/10.1542/peds.2006-2481Crossref PubMed Scopus (302) Google Scholar Multiple factors are associated with the onset of menarche in the general population. An inverse association between body mass index,32Ramezani Tehrani F. Mirmiran P. Gholami R. Moslehi N. Azizi F. Factors influencing menarcheal age: results from the cohort of Tehran lipid and glucose study.Int J Endocrinol Metab. 2014; 12: e16130https://doi.org/10.5812/ijem.16130Crossref PubMed Scopus (28) Google Scholar, 33Yermachenko A. Dvornyk V. 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Nongenetic determinants of age at menarche: a systematic review.BioMed Res Int. 2014; 2014: 371583https://doi.org/10.1155/2014/371583Crossref PubMed Scopus (99) Google Scholar onset of menarche. Urban residence and Black race/ethnicity have been associated with earlier menarche, although these differences may or may not be in part attributed to socioeconomic status.33Yermachenko A. Dvornyk V. Nongenetic determinants of age at menarche: a systematic review.BioMed Res Int. 2014; 2014: 371583https://doi.org/10.1155/2014/371583Crossref PubMed Scopus (99) Google Scholar,34Deardorff J. Abrams B. Ekwaru J.P. Rehkopf D.H. Socioeconomic status and age at menarche: an examination of multiple indicators in an ethnically diverse cohort.Ann Epidemiol. 2014; 24: 727-733https://doi.org/10.1016/j.annepidem.2014.07.002Crossref PubMed Scopus (50) Google Scholar,38Martinez G.M. Trends and patterns in menarche in the United States: 1995 through 2013–2017. Centers for Disease Control and Prevention.https://stacks.cdc.gov/view/cdc/93643Google Scholar,40Wu T. Mendola P. Buck G.M. Ethnic differences in the presence of secondary sex characteristics and menarche among US girls: the third National Health and Nutrition Examination Survey, 1988–1994.Pediatrics. 2002; 110: 752-757https://doi.org/10.1542/peds.110.4.752Crossref PubMed Scopus (276) Google Scholar Increasing reports reveal associations between both early and late menarche and adverse health outcomes, including risk of cardiovascular disease, CKD, and overall mortality.41Lakshman R. Forouhi N.G. Sharp S.J. et al.Early age at menarche associated with cardiovascular disease and mortality.J Clin Endocrinol Metab. 2009; 94: 4953-4960https://doi.org/10.1210/jc.2009-1789Crossref PubMed Scopus (326) Google Scholar, 42Noh J.H. Koo H. Older menarche age and short reproductive period linked to chronic kidney disease risk.Medicine. 2019; 98: e15511https://doi.org/10.1097/MD.0000000000015511Crossref PubMed Scopus (5) Google Scholar, 43Lee J.J. Cook-Wiens G. Johnson B.D. et al.Age at menarche and risk of cardiovascular disease outcomes: findings from the National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation.J Am Heart Assoc. 2019; 8e012406https://doi.org/10.1161/jaha.119.012406Crossref PubMed Scopus (0) Google ScholarGiven the multiple factors associated with onset of menarche, it is challenging to elucidate the association, if any, between CKD and onset of uterine bleeding. In a prospective cohort study of 57 female adolescents with stage 4 CKD and kidney failure treated with hemodialysis and peritoneal dialysis, Serret-Montaya et al.29Serret-Montaya J. Zurita-Cruz J.N. Villasís-Keever M.A. et al.Hyperprolactinemia as a prognostic factor for menstrual disorders in female adolescents with advanced chronic kidney disease.Pediatr Nephrol. 2020; 35: 1041-1049https://doi.org/10.1007/s00467-020-04494-7Crossref PubMed Scopus (1) Google Scholar reported a median age of menarche of 12 years after exclusion of participants with primary amenorrhea. The primary causes of CKD were glomerulonephritis (22.8%) and congenital abnormalities of the kidney and urinary tract (22.8%), and most participants had a healthy nutritional status. Although the median age of menarche was similar in those with and without abnormal uterine bleeding, information including estimated glomerular filtration rate, ethnicity, and socioeconomic status was not reported. In a cross-sectional study of 287 girls with CKD onset before menarche, the median age of menarche was 12 years, though 10% had delayed menarche (defined as menarche at ≥15 years), which was associated with African-American race, lower estimated glomerular filtration rate, corticosteroid use, and longer CKD duration, concluding delayed menarche may suggest a risk of short stature.44Kim H.S. Ng D.K. Matheson M.B. et al.Delayed menarche in girls with chronic kidney disease and the association with short stature.Pediatr Nephrol. 2020; 35: 1471-1475https://doi.org/10.1007/s00467-020-04559-7Crossref PubMed Scopus (7) Google ScholarFrom the perspective of nephrologists, being aware of age of menarche is an important consideration as the American Academy of Pediatrics has suggested that the menstrual cycle is a vital sign in female patients.31Diaz A. Laufer M.R. Breech L.L. et al.Menstruation in girls and adolescents: using the menstrual cycle as a vital sign.Pediatrics. 2006; 118: 2245-2250https://doi.org/10.1542/peds.2006-2481Crossref PubMed Scopus (302) Google Scholar Nevertheless, in a study of 75 nephrologists (95% pediatric, 5% adult) practicing in the United States and Puerto Rico, Vasylyeva et al.45Vasylyeva T.L. Page-Hefley S. Almaani S. et al.Evaluation of the reproductive care provided to adolescent patients in nephrology clinics: a pediatric nephrology research consortium study.Kidney Int Rep. 2021; 6: 1411-1415https://doi.org/10.1016/j.ekir.2021.02.007Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar reported that 17% never/rarely documented the age of menarche of adolescent patients and more than a third never/rarely documented the date of the patient's last menstrual period. This discrepancy highlights the need for nephrologists to take comprehensive menstrual histories, including age of menarche, to consider this sex-specific factor in the care of adolescents living with kidney disease.Kidney Disease and Abnormal Uterine BleedingAbnormal uterine bleeding is defined as any disruption of a healthy menstrual cycle in terms of the volume of blood loss, duration, frequency, and regularity of menses.22Hoffman B.L. Schorge J.O. Halvorson L.M. et al.Chapter 8: abnormal uterine bleeding.in: Williams Gynecology. 4th ed. McGraw-Hill Education LLC, 2020Google Scholar Abnormal uterine bleeding, particularly irregular or long (≥40 days) menstrual cycles, has been associated with premature mortality in comparison to regular or short cycles in the general population.46Wang Y.X. Arvizu M. Rich-Edwards J.W. et al.Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study.BMJ. 2020; 371: m3464https://doi.org/10.1136/bmj.m3464Crossref PubMed Scopus (16) Google Scholar Abnormal uterine bleeding is also associated with absenteeism in school and work.47Sharma P. Malhotra C. Taneja D.K. Saha R. Problems related to menstruation amongst adolescent girls.Indian J Pediatr. 2008; 75: 125-129https://doi.org/10.1007/s12098-008-0018-5Crossref PubMed Scopus (71) Google Scholar, 48Lee L.K. Chen P.C. Lee K.K. Kaur J. Menstruation among adolescent girls in Malaysia: a cross-sectional school survey.Singapore Med J. 2006; 47: 869-874PubMed Google Scholar, 49Tanaka E. Momoeda M. Osuga Y. et al.Burden of menstrual symptoms in Japanese women: results from a survey-based study.J Med Econ. 2013; 16: 1255-1266https://doi.org/10.3111/13696998.2013.830974Crossref PubMed Scopus (33) Google Scholar In the general population of reproductive-aged women, the estimated prevalence of abnormal uterine bleeding is at least 10% to 30%,50Liu Z. Doan Q.V. Blumenthal P. Dubois R.W. A systematic review evaluating health-related quality of life, work impairment, and health-care costs and utilization in abnormal uterine bleeding.Value Health. 2007; 10: 183-194https://doi.org/10.1111/j.1524-4733.2007.00168.xAbstract Full Text PDF PubMed Scopus (179) Google Scholar whereas heavy menstrual bleeding affects 30% of women throughout their reproductive lifespan.51Market Opinion and Research International (MORI). Women’s Health in 1990. [Research study conducted on behalf of Parke-Davis Laboratories]. MORI. Published 1990.Google Scholar Heavy menstrual bleeding is defined as the loss of ≥80 ml of blood on each menstrual cycle, which is clinically indicated by 1 or more of the following factors: bleeding that lasts >7 days, bleeding that soaks through ≥1 menstrual products every hour for several hours, bleeding that requires simultaneous use of multiple menstrual products to manage flow, bleeding that requires a change of menstrual product during the night, or the pr
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