Sections

Abnormal (Dysfunctional) Uterine Bleeding

Sections Abnormal (Dysfunctional) Uterine Bleeding
Overview
Presentation
DDx
Workup
Treatment
Medication
Questions & Answers
Tables
References

Workup

Laboratory Studies

Laboratory studies for patients with abnormal uterine bleeding (AUB) may include human chorionic gonadotropin (HCG), complete blood count (CBC), Pap smear, endometrial sampling, thyroid functions and prolactin, liver functions, coagulation studies/factors, and other hormone assays as indicated.^[43]

Human chorionic gonadotropin

The most common cause of abnormal uterine bleeding during the reproductive years is abnormal pregnancy. Rule out threatened abortion, incomplete abortion, and ectopic pregnancy.

Complete blood count

Document blood loss. Charting the number of menstrual pads used per day, or keeping a menstrual calendar is helpful.

Obtain a baseline CBC count for hemoglobin and hematocrit to evaluate for anemia. Obtain a differential with platelet count if hematologic disease is suspected.

Pap smear

Pap smear should be up to date. Cervical cancer still is the most common gynecologic cancer affecting women of reproductive age in the world population.

Endometrial sampling

Perform a biopsy to rule out endometrial hyperplasia or cancer in high-risk women aged ≥45 years and in younger women at extreme risk for endometrial hyperplasia/carcinoma due to unopposed estrogen (PCOS, obesity), failed medical management, and persistent AUB. Women with chronic eugonadal anovulation, obesity, hirsutism, diabetes, or chronic hypertension are at particular risk.

Most biopsies will confirm the absence of secretory endometrium.

Thyroid and liver function tests

Perform thyroid function tests and prolactin because hyperthyroidism, hypothyroidism, and hyperprolactinemia are associated with ovulatory dysfunction. Identify and treat these conditions.

Obtain liver function tests if alcoholism or hepatitis is suspected. Any condition affecting liver metabolism of estrogen can be associated with abnormal uterine bleeding.

Coagulation factors

Von Willebrand disease and factor XI deficiency initially might manifest during adolescence.

Primary or secondary thrombocytopenia can be factors in the mature patient.

Tailor the choice of laboratory tests to the presenting clinical situation. Generally speaking, when coagulopathies are present, heavy bleeding is regular and associated with ovulation.

Other hormone assays

For the patient with recurrent anovulatory bleeding, the mainstay of management is treatment of correctable disease.

Obtain a hormonal complete evaluation in women with signs of hyperandrogenism, such as those with polycystic ovarian syndrome, 21 hydroxylase deficiency, or ovarian or adrenal tumors, as dictated by their respective conditions.

Women in menopausal transition usually can be followed without an extensive hormonal evaluation.

Imaging Studies

Generally, patients with abnormal uterine bleeding can be managed appropriately without the use of expensive imaging studies.

Ultrasonography, especially saline infusion sonography, can be used to examine the status of the endometrium, myometrium, and ovaries. Endometrial hyperplasia, endometrial carcinoma, endometrial polyps, uterine fibroids, and ovarian cysts/masses can be suspected or diagnosed with this technology.

Procedures

Rule out endometrial carcinoma in all patients at high risk for the condition, including patients with the following characteristics:

Morbid obesity
Diabetes or chronic hypertension
Age >45 years
Longstanding, chronic eugonadal anovulation

Traditionally, carcinoma was ruled out by endometrial sampling via dilation and curettage (D&C). More recently, endometrial sampling in the office via aspiration, curetting, or hysteroscopy has become popular and is also relatively accurate.

Saline infusion sonography can be helpful in distinguishing individuals who have bleeding with thick endometrium from those with thin, denuded endometrium, endometrial polyps, uterine fibroids, or other uterine pathology.

Most endometrial biopsy specimens will show proliferative or dyssynchronous endometrium.

Treatment & Management

Munro MG, Critchley HO, Fraser IS. The FIGO classification of causes of abnormal uterine bleeding: Malcolm G. Munro, Hilary O.D. Crithcley, Ian S. Fraser, for the FIGO Working Group on Menstrual Disorders. Int J Gynaecol Obstet. 2011 Apr. 113 (1):1-2. [QxMD MEDLINE Link].
Munro MG, Critchley HO, Broder MS, Fraser IS, FIGO Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011 Apr. 113 (1):3-13. [QxMD MEDLINE Link].
Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med. 2011 Sep. 29 (5):383-90. [QxMD MEDLINE Link].
Shapley M, Jordan K, Croft PR. An epidemiological survey of symptoms of menstrual loss in the community. Br J Gen Pract. 2004 May. 54 (502):359-63. [QxMD MEDLINE Link]. [Full Text].
Frick KD, Clark MA, Steinwachs DM, et al. Financial and quality-of-life burden of dysfunctional uterine bleeding among women agreeing to obtain surgical treatment. Womens Health Issues. 2009 Jan-Feb. 19 (1):70-8. [QxMD MEDLINE Link].
[Guideline] Committee on Practice Bulletins—Gynecology. Practice bulletin no. 128: diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol. 2012 Jul. 120 (1):197-206. [QxMD MEDLINE Link].
Lieng M, Istre O, Qvigstad E. Treatment of endometrial polyps: a systematic review. Acta Obstet Gynecol Scand. 2010 Aug. 89 (8):992-1002. [QxMD MEDLINE Link].
Lieng M, Qvigstad E, Sandvik L, Jørgensen H, Langebrekke A, Istre O. Hysteroscopic resection of symptomatic and asymptomatic endometrial polyps. J Minim Invasive Gynecol. 2007 Mar-Apr. 14 (2):189-94. [QxMD MEDLINE Link].
Yu O, Schulze-Rath R, Grafton J, Hansen K, Scholes D, Reed SD. Adenomyosis incidence, prevalence and treatment: United States population-based study 2006-2015. Am J Obstet Gynecol. 2020 Jul. 223 (1):94.e1-94.e10. [QxMD MEDLINE Link].
Clarke MA, Long BJ, Del Mar Morillo A, Arbyn M, Bakkum-Gamez JN, Wentzensen N. Association of endometrial cancer risk with postmenopausal bleeding in women: a systematic review and meta-analysis. JAMA Intern Med. 2018 Sep 1. 178 (9):1210-22. [QxMD MEDLINE Link]. [Full Text].
Clarke MA, Long BJ, Sherman ME, et al. Risk assessment of endometrial cancer and endometrial intraepithelial neoplasia in women with abnormal bleeding and implications for clinical management algorithms. Am J Obstet Gynecol. 2020 Oct. 223 (4):549.e1-549.e13. [QxMD MEDLINE Link]. [Full Text].
Seravalli V, Linari S, Peruzzi E, Dei M, Paladino E, Bruni V. Prevalence of hemostatic disorders in adolescents with abnormal uterine bleeding. J Pediatr Adolesc Gynecol. 2013 Oct. 26 (5):285-9. [QxMD MEDLINE Link].
Shankar M, Lee CA, Sabin CA, Economides DL, Kadir RA. von Willebrand disease in women with menorrhagia: a systematic review. BJOG. 2004 Jul. 111 (7):734-40. [QxMD MEDLINE Link].
Jones K, Sung S. Anovulatory bleeding. StatPearls [Internet]. 2022 Jan. [QxMD MEDLINE Link]. [Full Text].
Kannar V, Lingaiah HK, Sunita V. Evaluation of endometrium for chronic endometritis by using syndecan-1 in abnormal uterine bleeding. J Lab Physicians. 2012 Jul. 4 (2):69-73. [QxMD MEDLINE Link]. [Full Text].
Melnikow J, Henderson JT, Burda BU, et al. Screening for Cervical Cancer With High-Risk Human Papillomavirus Testing: A Systematic Evidence Review for the US Preventive Services Task Force. Evidence Synthesis No. 158. AHRQ publication 15-05224-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2018.
Cepni I, Ocal P, Erkan S, et al. Comparison of transvaginal sonography, saline infusion sonography and hysteroscopy in the evaluation of uterine cavity pathologies. Aust N Z J Obstet Gynaecol. 2005 Feb. 45 (1):30-5. [QxMD MEDLINE Link].
Champaneria R, Abedin P, Daniels J, Balogun M, Khan KS. Ultrasound scan and magnetic resonance imaging for the diagnosis of adenomyosis: systematic review comparing test accuracy. Acta Obstet Gynecol Scand. 2010 Nov. 89 (11):1374-84. [QxMD MEDLINE Link].
Timmermans A, Opmeer BC, Khan KS, et al. Endometrial thickness measurement for detecting endometrial cancer in women with postmenopausal bleeding: a systematic review and meta-analysis. Obstet Gynecol. 2010 Jul. 116 (1):160-7. [QxMD MEDLINE Link].
Dijkhuizen FP, Mol BW, Brölmann HA, Heintz AP. The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer. 2000 Oct 15. 89 (8):1765-72. [QxMD MEDLINE Link].
Dumesic DA, Lobo RA. Cancer risk and PCOS. Steroids. 2013 Aug. 78 (8):782-5. [QxMD MEDLINE Link].
WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017 May 27. 389 (10084):2105-16. [QxMD MEDLINE Link]. [Full Text].
Zimmermann A, Bernuit D, Gerlinger C, Schaefers M, Geppert K. Prevalence, symptoms and management of uterine fibroids: an international internet-based survey of 21,746 women. BMC Womens Health. 2012 Mar 26. 12:6. [QxMD MEDLINE Link]. [Full Text].
Nijkang NP, Anderson L, Markham R, Manconi F. Endometrial polyps: Pathogenesis, sequelae and treatment. SAGE Open Med. 2019. 7:2050312119848247. [QxMD MEDLINE Link]. [Full Text].
Garcia L, Isaacson K. Adenomyosis: review of the literature. J Minim Invasive Gynecol. 2011 Jul-Aug. 18 (4):428-37. [QxMD MEDLINE Link].
Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003 Jan. 188 (1):100-7. [QxMD MEDLINE Link].
El Andaloussi A, Al-Hendy A, Ismail N, Boyer TG, Halder SK. Introduction of Somatic Mutation in MED12 Induces Wnt4/β-Catenin and Disrupts Autophagy in Human Uterine Myometrial Cell. Reprod Sci. 2020 Mar. 27 (3):823-32. [QxMD MEDLINE Link]. [Full Text].
[Guideline] American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice. Uterine Morcellation for Presumed Leiomyomas: ACOG Committee Opinion, Number 822. Obstet Gynecol. 2021 Mar 1. 137 (3):e63-e74. [QxMD MEDLINE Link].
DeMulder D, Ascher SM. Uterine Leiomyosarcoma: Can MRI Differentiate Leiomyosarcoma From Benign Leiomyoma Before Treatment?. AJR Am J Roentgenol. 2018 Dec. 211 (6):1405-15. [QxMD MEDLINE Link].
[Guideline] Practice Bulletin No. 149: Endometrial cancer. Obstet Gynecol. 2015 Apr. 125 (4):1006-26. [QxMD MEDLINE Link].
Deligeoroglou E, Karountzos V. Abnormal Uterine Bleeding including coagulopathies and other menstrual disorders. Best Pract Res Clin Obstet Gynaecol. 2018 Apr. 48:51-61. [QxMD MEDLINE Link].
Nurden AT, Nurden P. Congenital platelet disorders and understanding of platelet function. Br J Haematol. 2014 Apr. 165 (2):165-78. [QxMD MEDLINE Link].
[Guideline] Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004 Jan. 81 (1):19-25. [QxMD MEDLINE Link].
Krassas GE, Pontikides N, Kaltsas T, et al. Disturbances of menstruation in hypothyroidism. Clin Endocrinol (Oxf). 1999 May. 50 (5):655-9. [QxMD MEDLINE Link].
Kulshreshtha B, Pahuja I, Kothari D, et al. Menstrual Cycle Abnormalities in Patients with Prolactinoma and Drug-induced Hyperprolactinemia. Indian J Endocrinol Metab. 2017 Jul-Aug. 21 (4):545-50. [QxMD MEDLINE Link]. [Full Text].
Livingstone M, Fraser IS. Mechanisms of abnormal uterine bleeding. Hum Reprod Update. 2002 Jan-Feb. 8 (1):60-7. [QxMD MEDLINE Link].
Hickey M, Fraser IS. A functional model for progestogen-induced breakthrough bleeding. Hum Reprod. 2000 Aug. 15 Suppl 3:1-6. [QxMD MEDLINE Link].
Hill GA, Wheeler JM. Incidence of breakthrough bleeding during oral contraceptive therapy. J Reprod Med. 1991 Apr. 36 (4 Suppl):334-9. [QxMD MEDLINE Link].
Archer DF, Jensen JT, Johnson JV, Borisute H, Grubb GS, Constantine GD. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results. Contraception. 2006 Dec. 74 (6):439-45. [QxMD MEDLINE Link].
Rosenberg M, Waugh MS. Causes and consequences of oral contraceptive noncompliance. Am J Obstet Gynecol. 1999 Feb. 180 (2 Pt 2):276-9. [QxMD MEDLINE Link].
Soules MR, Sherman S, Parrott E, et al. Stages of Reproductive Aging Workshop (STRAW). J Womens Health Gend Based Med. 2001 Nov. 10 (9):843-8. [QxMD MEDLINE Link].
Hale GE, Zhao X, Hughes CL, Burger HG, Robertson DM, Fraser IS. Endocrine features of menstrual cycles in middle and late reproductive age and the menopausal transition classified according to the Staging of Reproductive Aging Workshop (STRAW) staging system. J Clin Endocrinol Metab. 2007 Aug. 92 (8):3060-7. [QxMD MEDLINE Link].
Deligeoroglou EK, Creatsas GK. Dysfunctional uterine bleeding as an early sign of polycystic ovary syndrome during adolescence. Minerva Ginecol. 2015 Aug. 67 (4):375-81. [QxMD MEDLINE Link].
Maslyanskaya S, Talib HJ, Northridge JL, Jacobs AM, Coble C, Coupey SM. Polycystic Ovary Syndrome: An Under-recognized Cause of Abnormal Uterine Bleeding in Adolescents Admitted to a Children's Hospital. J Pediatr Adolesc Gynecol. 2017 Jun. 30 (3):349-355. [QxMD MEDLINE Link].
Roach L. Uterine Bleeding: ACOG Updates Guidelines. Medscape Medical News. Jun 21 2013. Available at http://www.medscape.com/viewarticle/806735. Accessed: July 10, 2013.
Committee on Practice Bulletins—Gynecology. Practice bulletin no. 136: management of abnormal uterine bleeding associated with ovulatory dysfunction. Obstet Gynecol. 2013 Jul. 122 (1):176-85. [QxMD MEDLINE Link].
Hickey M, Higham JM, Fraser I. Progestogens with or without oestrogen for irregular uterine bleeding associated with anovulation. Cochrane Database Syst Rev. 2012 Sep 12. 9:CD001895. [QxMD MEDLINE Link].
Jick SS, Hernandez RK. Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data. BMJ. 2011 Apr 21. 342:d2151. [QxMD MEDLINE Link]. [Full Text].
Bennett AR, Gray SH. What to do when she's bleeding through: the recognition, evaluation, and management of abnormal uterine bleeding in adolescents. Curr Opin Pediatr. 2014 Aug. 26 (4):413-9. [QxMD MEDLINE Link].
Jain S, Vaid NB, Narang Y, Suneja A, Guleria K. A Randomised Controlled Trial Comparing the Efficacy and Side-Effects of Intravaginal Ring (Nuvaring(®)) With Combined Oral Hormonal Preparation in Dysfunctional Uterine Bleeding. J Clin Diagn Res. 2016 Mar. 10 (3):QC21-4. [QxMD MEDLINE Link]. [Full Text].
Teichmann A, Apter D, Emerich J, Greven K, Klasa-Mazurkiewicz D, Melis GB, et al. Continuous, daily levonorgestrel/ethinyl estradiol vs. 21-day, cyclic levonorgestrel/ethinyl estradiol: efficacy, safety and bleeding in a randomized, open-label trial. Contraception. 2009 Dec. 80(6):504-11. [QxMD MEDLINE Link].
Hokenstad AN, El-Nashar SA, Khan Z, Hopkins MR, Famuyide AO. Endometrial ablation in women with abnormal uterine bleeding related to ovulatory dysfunction: a cohort study. J Minim Invasive Gynecol. 2015 Nov-Dec. 22 (7):1225-30. [QxMD MEDLINE Link].
Vitagliano A, Bertin M, Conte L, et al. Thermal balloon ablation versus transcervical endometrial resection: evaluation of postoperative pelvic pain in women treated for dysfunctional uterine bleeding. Clin Exp Obstet Gynecol. 2014. 41(4):405-8. [QxMD MEDLINE Link].
Athanatos D, Pados G, Venetis CA, et al. Novasure impedance control system versus microwave endometrial ablation for the treatment of dysfunctional uterine bleeding: a double-blind, randomized controlled trial. Clin Exp Obstet Gynecol. 2015. 42 (3):347-51. [QxMD MEDLINE Link].

Media Gallery

of 0

Table. Physical Findings in AUB

Table. Physical Findings in AUB

Examination	Finding	Differential
Vital signs	Tachycardia	Anemia Hypovolemia
Weight	Obesity	PCOS, weight-related anovulation
Eyes	Exophthalmos Periorbital edema	Graves disease Hypothyroidism
Neck	Thyromegaly	Hypothyroidism
Breasts	Galactorrhea	Hyperprolactinemia
Skin	Increased skin tags Acanthosis nigricans Hirsutism Ecchymosis, purpura	PCOS Insulin resistance PCOS, CAH, Cushing syndrome, androgen-secreting tumor Bleeding disorder
Pelvic examination	Cervical polyp/cervicitis/cervical ectropion Globally enlarged uterus Irregular uterus Adnexal mass	Adenomyosis Fibroids Ovarian cyst or mass
AUB = abnormal uterine bleeding; CAH = congenital adrenal hyperplasia; PCOS = polycystic ovary syndrome.

Back to List

Author

Thomas Michael Price, MD Professor Emeritus, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Former Director of Reproductive Endocrinology and Infertility Fellowship Program, Duke University Medical Center

Thomas Michael Price, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Phi Beta Kappa, Society for Reproductive Endocrinology and Infertility, Society for Reproductive Investigation

Disclosure: Received research grant from: Insigtec Inc<br/>Received consulting fee from Clinical Advisors Group for consulting; Received consulting fee from MEDA Corp Consulting for consulting; Received consulting fee from Gerson Lehrman Group Advisor for consulting; Received honoraria from ABOG for board membership.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Frances E Casey, MD, MPH Associate Professor, Director of Family Planning Services, Department of Obstetrics and Gynecology, VCU Medical Center

Frances E Casey, MD, MPH is a member of the following medical societies: American College of Obstetricians and Gynecologists, Association of Reproductive Health Professionals, National Abortion Federation, Physicians for Reproductive Health, Society of Family Planning

Disclosure: Nothing to disclose.

Chief Editor

Richard Scott Lucidi, MD, FACOG Associate Professor of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine

Richard Scott Lucidi, MD, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Anthony Charles Sciscione, DO Professor, Department of Obstetrics and Gynecology, Drexel University College of Medicine; Director, Maternal and Fetal Medicine, Christiana Care Health System; Director, Delaware Center for Maternal and Fetal Medicine

Anthony Charles Sciscione, DO is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association

Disclosure: Nothing to disclose.

Millie A Behera, MD Assistant Professor (Adjunct), Division of Reproductive Endocrinology and Fertility, Department of Obstetrics and Gynecology, Duke University Medical Center; Medical Director, Bloom Reproductive Institute

Millie A Behera, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, AAGL

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Drugs & Diseases gratefully acknowledge the contributions of previous author John T Queenan, Jr, MD, to the development and writing of this article.