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Abnormal (Dysfunctional) Uterine Bleeding Medication

  • Author: Millie A Behera, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
 
Updated: Nov 15, 2015
 

Medication Summary

Estrogens, progestins, androgens, nonsteroidal anti-inflammatory drugs (NSAIDs), ergot derivatives, antifibrinolytics, and gonadotropin-releasing hormone (GnRH) agonists have been used to treat abnormal uterine bleeding (AUB). More recently, desmopressin has been used to control bleeding when associated with diagnosed bleeding disorders that do not respond entirely to traditional management.

Ergot derivatives are not recommended for treatment of AUB because they have been shown to be effective rarely in clinical studies and have many side effects.

At the onset of menses, secretory endometrium contains a high concentration of plasminogen activator. A reduction in menstrual blood loss has been demonstrated in some ovulatory patients taking ε -aminocaproic acid (EACA) or aminomethylcyclohexane-carboxylic acid (AMCHA) tranexamic acid, both potent antifibrinolytics. However, this therapeutic effect was no greater than that seen with oral contraceptive therapy. Antifibrinolytics are associated with significant side effects, such as severe nausea, diarrhea, headache, and allergic manifestations, and cannot be used in patients with renal failure. Because of the high side-effect profile and expense, these agents rarely are used today for this indication.

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Estrogens

Class Summary

Very effective in controlling acute, profuse bleeding. Exerts a vasospastic action on capillary bleeding by affecting the level of fibrinogen, factor IV, and factor X in blood, as well as platelet aggregation and capillary permeability. Estrogen also induces formation of progesterone receptors, making subsequent treatment with progestins more effective.

Most AUB is secondary to anovulation. In these patients, endometrium continues to proliferate with asynchronous development. As blood supply is outgrown, irregular shedding occurs. Bleeding might be controlled acutely with high-dose estrogen for a short period of time. Several hours are required to induce mitotic activity, so most regimens require 48 h of therapy before continued bleeding is ruled a treatment failure.

Estrogen therapy only controls bleeding acutely and does not treat underlying cause. Appropriate long-term therapy can be administered once the acute episode has passed.

Conjugated equine estrogen (Premarin)

 

Women in perimenopause generally are estrogen deficient and might experience bouts of estrogen withdrawal bleeding. Many of these patients will recover regular menses and develop an improved sense of well-being with the initiation of hormonal replacement therapy, including estrogen and a progestin.

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Progestins

Class Summary

Occasional anovulatory bleeding that is not profuse or prolonged can be treated with progestins. Progestins inhibit estrogen receptor replenishment and activate 17-hydroxysteroid dehydrogenase in endometrial cells, converting estradiol to the less active estrone. Medroxyprogesterone acetate (Provera) is the most commonly used progestin in this country, but other types, including norethindrone acetate (Aygestin) and norethindrone (Micronor), are equally efficacious. In some patients in which systemic progestins are intolerable due to side effects, a progestin secreting IUD (Mirena) may be considered.

Synthetic progestins have an antimitotic effect, allowing the endometrium to become atrophic if administered continuously. These drugs are very effective in cases of endometrial hyperplasia. In patients with chronic eugonadal anovulation who do not desire pregnancy, treatment with a progestin for 10-12 d/mo will allow for controlled, predictable menses and will protect the patient against the development of endometrial hyperplasia.

Some perimenopausal patients will not respond well to progestin therapy because of an inherent estrogen deficiency. Also, patients with thin, denuded endometrium occurring after several days of chronic bleeding might require induction of new endometrial proliferation by estrogen therapy first.

Avoid synthetic progestins in early pregnancy. They induce an endometrial response that is different from normal preimplantation secretory endometrium. Also, several reports suggest an association between intrauterine exposure to synthetic progestins in the first trimester of pregnancy and genital abnormalities in male and female fetuses. The risk of hypospadias, 5-8 per 1000 male births, might be doubled with early in-utero exposure to these drugs. Some synthetic progestins might cause virilization of female external genitalia in utero.

Patients at risk for conception can be treated safely with natural progesterone preparations. These preparations induce a normal secretory endometrium appropriate for implantation and subsequent growth of a developing conceptus.

Medroxyprogesterone acetate (Provera)

 

Short-acting synthetic progestin. Drug of choice for patients with anovulatory AUB. After acute bleeding episode is controlled, can be used alone in patients with adequate amounts of endogenous estrogen to cause endometrial growth. Progestin therapy in adolescents produces regular cyclic withdrawal bleeding until positive feedback system matures.

Stops endometrial cell proliferation, allowing organized sloughing of cells after withdrawal. Typically does not stop acute bleeding episode but produces a normal bleeding episode following withdrawal.

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Combination oral contraceptives

Class Summary

Contraceptive pills containing estrogen and progestin have been advocated for nonsmoking patients with AUB who desire contraception. Therapy also used to treat acute hemorrhagic uterine bleeding but is not as effective as regimens previously mentioned. Apparently takes longer to induce endometrial proliferation when progestin is present. In long-term management of AUB, combination oral contraceptives are very effective.

Ethinyl estradiol and a progestin derivative (examples: Ovral, Lo-Ovral, Ortho-Novum, Ovcon, Genora, Orthocyclen, and others)

 

Reduces secretion of LH and FSH from pituitary by decreasing amount of GnRH.

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Androgens

Class Summary

Certain androgenic preparations have been used historically to treat mild to moderate bleeding, particularly in ovulatory patients with abnormal uterine bleeding. These regimens offer no real advantage over other regimens and might cause irreversible signs of masculinization in the patient. They seldom are used for this indication today.

Use of androgens might stimulate erythropoiesis and clotting efficiency. Androgens alter endometrial tissue so that it becomes inactive and atrophic.

Danazol (Danocrine)

 

Isoxazole derivative of 12 alpha-ethinyl testosterone.

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Nonsteroidal anti-inflammatory drugs

Class Summary

Blocks formation of prostacyclin, an antagonist of thromboxane, which is a substance that accelerates platelet aggregation and initiates coagulation. Prostacyclin is produced in increased amounts in menorrhagic endometrium. Because NSAIDs inhibit blood prostacyclin formation, they might effectively decrease uterine blood flow. NSAIDs have been shown to treat menorrhagia in ovulatory cycles but generally are not effective for the management of AUB.

Naproxen (Anaprox, Naprelan, Naprosyn)

 

Used for relief of mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which is responsible for prostaglandin synthesis.

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GnRH agonists

Class Summary

Work by reducing concentration of GnRH receptors in the pituitary via receptor down regulation and induction of postreceptor effects, which suppress gonadotropin release. After an initial gonadotropin release associated with rising estradiol levels, gonadotropin levels fall to castrate levels, with resultant hypogonadism. This form of medical castration is very effective in inducing amenorrhea, thus breaking ongoing cycle of abnormal bleeding in many anovulatory patients. Because prolonged therapy with this form of medical castration is associated with osteoporosis and other postmenopausal side effects, its use is often limited in duration and add back therapy with a form of low-dose hormonal replacement is given. Because of the expense of these drugs, they usually are not used as a first line approach but can be used to achieve short-term relief from a bleeding problem, particularly in patients with renal failure or blood dyscrasia.

Depot leuprolide acetate (Lupron)

 

Suppresses ovarian steroidogenesis by decreasing LH and FSH levels.

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Arginine vasopressin derivatives

Class Summary

Indicated in patients with thromboembolic disorders.

Desmopressin acetate (DDAVP)

 

Has been used to treat abnormal uterine bleeding in patients with coagulation defects. Transiently elevates factor VIII and von Willebrand factor.

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Contributor Information and Disclosures
Author

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.

Coauthor(s)

Thomas Michael Price, MD Associate Professor, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, 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, Phi Beta Kappa, Society for Reproductive Investigation, Society for Reproductive Endocrinology and Infertility, American Society for Reproductive Medicine

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 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, Society of Family Planning, National Abortion Federation, Physicians for Reproductive Health

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.

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.

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