Version July 2025
INTRODUCTION —
Menstrual disorders and abnormal uterine bleeding are among the most frequent gynecologic concerns in adolescents. Anovulatory uterine bleeding is a subset of abnormal uterine bleeding and is a diagnosis of exclusion. Anovulatory uterine bleeding is characterized by noncyclic menstrual blood flow that occurs when sex steroid production is not synchronized. It can present with either oligomenorrhea or amenorrhea or with prolonged bleeding. Immaturity of the hypothalamic-pituitary-ovarian (HPO) axis is the most common cause of anovulatory uterine bleeding in adolescents (figure 1) [1-3].
The management of prolonged, moderate to heavy anovulatory uterine bleeding in otherwise healthy adolescents is the focus of this topic review. The normal menstrual cycle, evaluation of abnormal uterine bleeding in adolescents, and evaluation and management of other causes of abnormal uterine bleeding are discussed separately:
●(See "Abnormal uterine bleeding in adolescents: Evaluation and approach to diagnosis".)
●(See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management".)
The management of abnormal uterine bleeding in adolescents with chronic disease, underlying coagulation disorders, and those receiving a hematopoietic stem cell transplantation or undergoing chemotherapy should be conducted in collaboration with the appropriate subspecialist. (See "von Willebrand disease (VWD): Gynecologic and obstetric considerations" and "Management of menorrhagia during chemotherapy".)
PRETREATMENT EVALUATION —
Prior to initiating treatment for acute anovulatory uterine bleeding, the following should be addressed:
●Exclude pregnancy and pelvic infections [2]
●Evaluate for other causes of abnormal uterine bleeding (table 1) (see "Abnormal uterine bleeding in adolescents: Evaluation and approach to diagnosis")
●If a bleeding disorder evaluation is indicated, obtain required blood samples before administration of blood products or estrogen (exogenous estrogen may elevate von Willebrand factor into the normal range) [4,5]
BLEEDING SEVERITY CLASSIFICATION —
Selection of the acute management regimen depends upon the severity of anovulatory bleeding, which we classify as follows:
●Mild [6]
•Slightly or moderately increased menstrual flow (table 2)
•Menstrual flow >7 days or day one of cycles occurs <24 days apart for ≥2 months
•Hemoglobin is usually normal (≥12 g/dL) but may be mildly decreased (10 to 12 g/dL)
●Moderate [2,6]
•Moderate to heavy menstrual flow
•Menstrual flow >7 days or cycles occur every one to three weeks
•Hemoglobin is usually ≥10 g/dL and <12 g/dL
●Severe [2,6]
•Heavy menstrual flow that may or may not cause hemodynamic instability
•Menstrual flow >7 days
•Hemoglobin is usually <10 g/dL
Quantifying menstrual blood flow is challenging. Indicators of heavy menstrual flow include passing blood clots larger than 2.5 cm (1 inch) in diameter, bleeding through clothes, and needing to change sanitary protection during the night. Heavy blood flow interferes with activities and/or physical, emotional, or social quality of life.
MANAGEMENT OF MILD TO MODERATE ANOVULATORY UTERINE BLEEDING
Mild bleeding — Most patients with mild bleeding do not require hormonal therapy and can be managed with observation [7,8].
For patients whose quality of life is impacted or who desire contraception for current or anticipated sexual activity, we use the same hormonal therapy regimens as for patients who have moderate bleeding without active bleeding. (See 'Not currently bleeding' below.)
Some patients with mild bleeding have mild anemia (hemoglobin between 10 to 12 g/dL). The decision to initiate hormonal therapy or observe is individualized according to patient and caregiver preferences. These patients should receive iron supplementation. (See "Iron requirements and iron deficiency in adolescents".)
We encourage patients with mild anovulatory uterine bleeding to keep a menstrual calendar (paper (figure 2) or mobile phone application [app] [9]) to monitor the frequency and flow of menses and the response to hormonal therapy.
We schedule a follow-up visit three to six months after the initial visit to assess menstrual patterns and the effectiveness of hormonal therapy (if started). Once the patient's menstrual pattern is stable, we schedule follow-up visits annually and advise patients to call for an urgent visit if the flow, frequency, or volume of menses increases at any point.
Moderate bleeding — Most adolescents with moderate anovulatory uterine bleeding respond to hormonal therapy [4,10]. However, there is no consensus about the optimal approach. Doses of estrogen, type of progestin, and schedule of administration vary widely.
The hormonal therapy regimen that we use depends upon whether the patient is currently bleeding [11].
We advise all patients to use a paper menstrual calendar (figure 2) or one of several freely available smart phone apps [9,12] to monitor subsequent episodes of anovulatory uterine bleeding. A menstrual calendar may also serve as a reminder of when to take hormonal medication.
Iron therapy to treat anemia should be initiated. (See "Iron requirements and iron deficiency in adolescents".)
Not currently bleeding — Decisions regarding management in patients who are not actively bleeding are individualized according to the preferences of the patient and caregiver and whether contraception is desired for current or anticipated sexual activity.
If contraception is not desired, progestin-only and combined estrogen-progestin regimens are equally appropriate choices. There have been no trials comparing the effectiveness of combined estrogen-progestin regimens with progestin-only regimens for the treatment of anovulatory bleeding in adolescents. However, a trial among 40 adults demonstrated a marginally (but not statistically significant) increased response rate to combined oral contraceptive (COC) pills versus progestin-only pills (88 versus 76 percent; relative risk [RR] 1.1, 95% CI 0.8-1.8) [13].
If contraception is desired and estrogen is not contraindicated, we suggest a combined estrogen-progestin contraceptive. The contraceptive patch or vaginal ring are acceptable alternatives for patients who prefer a contraceptive option that does not require daily use. If estrogen is contraindicated (eg, migraine with aura, systemic lupus erythematosus with positive or unknown antiphospholipid antibodies, arterial or venous thromboembolic disease, estrogen-dependent tumors, and hepatic dysfunction or disease), we use a daily progestin-only contraceptive regimen. A hormonal intrauterine device (IUD) or depot medroxyprogesterone are alternative options for these patients or for those who do not want to take a pill every day. (See "Contraception: Overview of issues specific to adolescents", section on 'Long-acting reversible methods'.)
●Estrogen-containing oral option – We prescribe monophasic oral contraceptive pills with an ethinyl estradiol dose of 30 to 35 mcg. This dose provides a sufficient amount of estrogen to minimize breakthrough bleeding and maintain bone health (table 3) [1].
We instruct patients to take one pill every day and use all of the pills in the package, including the placebo pills.
We advise against the use of continuous hormonally active pills because this is commonly associated with breakthrough bleeding. The patient is likely to interpret the breakthrough bleeding as a failure of therapy, which may lead to discontinuation.
●Oral progestin-only options
•Daily options with contraceptive efficacy
-Norethindrone 0.35 mg once daily; effective for contraception when taken consistently
-Drospirenone 4 mg once daily for 24 days followed by an inactive pill once daily for four days
We advise patients that irregular spotting and bleeding is not uncommon, particularly if pills are missed, but if heavy vaginal bleeding occurs, they should schedule a follow-up visit to reevaluate treatment options.
•Cyclic options (no proven contraceptive efficacy) (table 4)
-Norethindrone acetate 5 mg daily for the first 5 to 10 days of each calendar month
-Micronized progesterone 200 mg daily for the first 12 days of each calendar month
-Medroxyprogesterone acetate 10 mg daily for the first 10 days of each calendar month
Norethindrone acetate helps to stabilize the endometrium and, in our experience, is usually effective within one to two days for most patients. Oral micronized progesterone is chemically identical to endogenous progesterone for those patients who prefer a more bioidentical approach. Medroxyprogesterone is another commonly used option but is less effective than norethindrone acetate. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management", section on 'Oral progestins'.)
Scheduling pills to start on the first day of each calendar month is easier for the patient to remember than an every-four-week schedule.
We advise patients who do not desire contraception to continue their progestin-only method for at least six months.
The first follow-up visit is scheduled approximately three months after the initial episode of bleeding to assess bleeding patterns and response to hormonal therapy. Once the bleeding pattern is stable, patient follow-up visits are scheduled annually.
Currently bleeding — For patients who are actively bleeding, we suggest combined estrogen-progestin oral contraceptives as first-line therapy because the estrogen component may provide greater hemostasis than progestin alone.
Progestin-only therapy is an alternative for patients who cannot tolerate or have a contraindication to estrogen (eg, migraine with aura, systemic lupus erythematosus, hepatic dysfunction or disease) [14,15].
We counsel patients that cyclic oral progestin-only regimens do not provide contraception. However, the 52 mg levonorgestrel (LNG) IUD provides both contraception and stabilization of bleeding. Many gynecologists, family medicine providers, and adolescent medicine providers offer the 52 mg LNG IUD for immediate management of acute bleeding. However, few pediatric offices have providers who can perform same-day IUD placement. (See "Contraception: Overview of issues specific to adolescents", section on 'Long-acting reversible methods'.)
Treatment with tranexamic acid (TXA) is an option for patients who decline all hormonal treatments.
●Estrogen-containing oral option – We prescribe a monophasic oral contraceptive pill with an ethinyl estradiol dose of 30 to 35 mcg. This dose provides a sufficient amount of estrogen to prevent breakthrough bleeding and maintain bone health (table 3) [1].
No trials have evaluated the treatment of anovulatory uterine bleeding in adolescents. However, in a meta-analysis of two trials (363 adults) comparing the effect of COCs with placebo for the treatment of heavy menstrual bleeding, the response rate was higher in the COC group than the placebo group (42 versus 3 percent; odds ratio 22, 95% CI 4-111) [16].
We use the following tapering regimen (hormonally active pills only); other tapering regimens have been described [2,17-21]:
•One pill every eight hours until the bleeding stops (usually within 48 hours), then
•One pill every 12 hours for two days, then
•One pill daily for 21 days, followed by seven days of one hormonally inactive pill daily to induce a withdrawal bleed
A planned withdrawal bleed allows for the shedding of what may be a dyssynchronous proliferated endometrium. Following the withdrawal bleed, we advise patients to continue cycles of 21 days of hormonally active pills with 7 days of inactive pills until the first follow-up visit.
Close follow-up is essential until the patient is taking only one pill per day.
We recommend that patients and caregivers receive written instructions detailing the steps of the taper that they can refer to as needed. We include instructions on when to go to the emergency department (eg, fainting, shortness of breath, light-headedness) and how to contact the office (with phone numbers) during clinic hours and after hours.
We instruct the patient and caregivers to contact the provider if nausea occurs so that an antiemetic can be prescribed. The high doses of estrogen used during the taper often cause nausea, which may lead to decreased adherence if not treated [2]. We use either ondansetron 4 to 8 mg orally or promethazine 12.5 to 25 mg orally or per rectum. The antiemetic should be taken one hour before each dose of hormone.
We further instruct the patient and caregiver to call the provider if bleeding increases or recurs during the taper. If bleeding recurs or increases, we temporarily increase the total daily dose (ie, number of pills per day) to the lowest dose that controls bleeding [11].
We schedule the first follow-up visit approximately one to three months after the initial episode of bleeding to assess bleeding patterns, response to hormonal therapy, and initiation of maintenance therapy. For patients who have established a cyclic menstrual pattern with reduced flow, monthly cycles are continued with yearly follow-up.
Alternatively, the patient may prefer to use continuous hormonally active pills for ongoing menstrual suppression. If so, it is important to help the patient understand the difference between the breakthrough bleeding that occurs during continuous pill use and the abnormal bleeding they experienced prior to oral contraceptive use.
If a cyclic pattern has not been established or flow is not reduced, we change the progestin to one that has more progestational activity (eg, norgestrel or LNG) or increase the number of COC pills per day to the lowest dose that controls bleeding. Follow-up visits continue every three to six months until the menstrual pattern is stable and are then scheduled yearly.
If the menstrual pattern has not improved because the patient has difficulty taking a daily pill, we discuss the 52 mg LNG IUD or depot medroxyprogesterone acetate (DMPA) as possible options. (See "Contraception: Overview of issues specific to adolescents".)
●Progestin-only options – We prescribe 5 to 10 mg of oral norethindrone acetate daily until the bleeding stops and hemoglobin is ≥12 g/dL. Among the oral progestin-only regimens (table 4), we prefer norethindrone acetate because it provides enough estrogenic activity to minimize irregular and unpredictable bleeding but not enough to stimulate endometrial bleeding. We educate patients that continuous norethindrone acetate has not been proven to be an effective contraceptive. Alternatively, a 52 mg LNG IUD can be placed if the adolescent prefers and if a trained provider is available.
We counsel patients that irregular spotting may occur initially. However, if they have heavy or prolonged vaginal bleeding, they should contact our office to schedule an urgent follow-up visit to consider a dose increase and/or the addition of TXA.
Once the bleeding is controlled, we advise a five- to seven-day pause of hormones to permit the shedding of the endometrium. If this causes heavy or prolonged bleeding, an urgent follow-up visit should be scheduled.
Once endometrial shedding has occurred and if the patient desires a cyclic bleed or needs contraception, we transition to a cyclic oral progestin-only regimen or a daily oral progestin-only contraceptive, respectively (table 4).
•Cyclic options (no proven contraceptive efficacy)
-Norethindrone acetate 5 mg daily for the first 5 to 10 days of each calendar month
-Micronized progesterone 200 mg daily for the first 12 days of each calendar month
-Medroxyprogesterone acetate 10 mg orally for the first 10 days of each calendar month
Scheduling pills to start on the first day of each calendar month is easier for the patient to remember than an every-four-week schedule.
•Daily options with contraceptive efficacy
-Norethindrone 0.35 mg once daily; effective for contraception when taken consistently
-Drospirenone 4 mg once daily for 24 days followed by inactive pill once daily for four days
We advise patients who do not desire contraception to continue their progestin-only method for at least six months.
Follow-up is scheduled one to three months after the initial bleeding episode to assess response to therapy. Follow-up visits continue every three to six months until bleeding stabilizes and are then scheduled annually.
If the patient prefers a longer-acting method or prefers not to take a daily pill, we discuss additional options, including long-acting reversible contraceptive (LARC) methods or injectable depot medroxyprogesterone. (See "Contraception: Overview of issues specific to adolescents".)
●TXA – We reserve treatment with cyclic TXA for patients who are unable to take or who decline hormonal options and do not have risk factors for thromboembolism [17]. The dose is 1300 mg orally, and it is taken up to three times per day during the first one to five days of each menstrual bleed. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management", section on 'Tranexamic acid' and "Managing an episode of acute uterine bleeding", section on 'Tranexamic acid'.)
No evidence is available to guide the duration of cyclic TXA therapy for adolescents with heavy menstrual bleeding.
We schedule an initial follow-up visit in one to three months to monitor hemoglobin. The addition of hormonal therapy may be necessary if hemoglobin continues to decline or fails to stabilize.
If hemoglobin is still low at the initial follow-up visit, we continue to schedule visits every one to three months until the anemia resolves. Once the anemia resolves, we follow up every 6 to 12 months. If the patient decides to discontinue TXA, we follow up in six months to ensure that the hemoglobin remains stable.
Although further research is warranted, evidence supports the very low risk of thromboembolism in patients who are taking concurrent COCs and TXA [22,23].
Cyclic TXA does not regulate menstrual cycles. However, in a small pilot study, it appeared to be as effective as combined estrogen-progestin in reducing menstrual blood loss and improving quality of life in adolescents with heavy menstrual bleeding [24]. A network meta-analysis found moderate quality evidence that antifibrinolytics probably reduce menstrual blood loss in patients with heavy menstrual bleeding [25].
If the patient's bleeding does not respond to hormonal therapy and/or TXA, an alternative diagnosis (eg, bleeding disorder, polycystic ovary syndrome, infection, uterine pathology) should be considered. Additional evaluation and consultation may be necessary [11]. (See "Abnormal uterine bleeding in adolescents: Evaluation and approach to diagnosis".)
MANAGEMENT OF SEVERE ANOVULATORY UTERINE BLEEDING —
Control of severe anovulatory uterine bleeding generally requires hormonal therapy at a minimum. It may also require hemostatic agents and (rarely) surgical intervention. Iron therapy to treat anemia should be initiated as soon as possible and is available as an intravenous (IV) infusion and oral tablets. (See "Iron requirements and iron deficiency in adolescents".)
Indications for hospitalization — Indications for hospitalization include [2,7,26,27]:
●Hemodynamic instability (eg, tachycardia, hypotension, orthostatic vital signs)
●Hemoglobin concentration <7 g/dL or <10 g/dL with active heavy bleeding
●Symptomatic anemia (eg, fatigue, lethargy)
●Need for IV conjugated estrogen (eg, cannot take oral medications, continued heavy bleeding after 24 hours of oral estrogen-progestin combination therapy) (see 'Preferred' below and 'Alternatives' below)
●Need for surgical intervention (see 'Management of refractory uterine bleeding' below)
Hospital discharge may be considered once the patient is hemodynamically stable, has a hemoglobin concentration ≥7 g/dL, and bleeding has been controlled. We schedule the first follow-up visit for two weeks after discharge.
Bleeding disorder evaluation — Patients who require hospitalization for anovulatory uterine bleeding require an evaluation for a bleeding disorder because bleeding disorders are more commonly the etiology when bleeding is severe. A hematology consult is also helpful. (See "Abnormal uterine bleeding in adolescents: Evaluation and approach to diagnosis", section on 'Heavy menstrual bleeding'.)
Blood samples for the laboratory evaluation of bleeding disorders should ideally be obtained before the administration of blood products or estrogen. Exogenous estrogen may elevate von Willebrand factor into the normal range, disguising the underlying diagnosis [4,5]. (See 'Pretreatment evaluation' above and "von Willebrand disease (VWD): Gynecologic and obstetric considerations", section on 'Heavy menstrual bleeding'.)
Hormonal therapy — We suggest hormonal therapy as the initial intervention for patients with severe anovulatory uterine bleeding, whether they are hospitalized or treated as outpatients. Hormonal therapy generally suppresses severe bleeding rapidly enough that hemostatic agents and/or surgical intervention are not required [16].
Venous thromboembolism risk — Although most adolescents have a low baseline risk for venous thromboembolism (VTE), ethinyl estradiol is associated with a small increase in risk from baseline. Patients with certain chronic or inherited medical conditions (table 5) should avoid using ethinyl estradiol because their baseline risk for VTE is higher.
The VTE risk associated with ethinyl estradiol appears to be dose-dependent. Consequently, the doses required to manage severe anovulatory uterine bleeding may markedly increase adolescents' risk for VTE compared with baseline. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Venous thromboembolism'.)
Choice of therapy
Preferred — We suggest combined oral contraceptive (COC) pills as the first line of hormonal therapy for severe bleeding because the estrogen component provides hemostasis and bleeding usually subsides within 48 hours [16].
Progestin-only therapy and IV conjugated estrogen are potential alternatives for patients who cannot take COC pills. (See 'Alternatives' below.)
We start with a monophasic COC containing 30 to 35 mcg of ethinyl estradiol and either 0.3 mg norgestrel or 0.4 to 1 mg norethindrone (table 3). This combination promotes rapid control of bleeding.
We use the following tapering regimen (hormonally active pills only); other tapering regimens have been described [2,17-21]:
●One pill every four to six hours until the bleeding subsides (usually within 24 hours), then
●One pill every eight hours for three days, then
●One pill every 12 hours for up to two weeks, then
●One pill once per day until maintenance therapy is initiated (see 'Maintenance therapy once bleeding is controlled' below)
During the tapering regimen, the hormonally active pills are taken continuously to avoid withdrawal menses, and we instruct the adolescent to discard the pills that do not contain hormone (ie, placebo pills).
No trials have evaluated the treatment of anovulatory uterine bleeding in adolescents. However, in a meta-analysis of two trials (363 adults) comparing the effect of COCs with placebo for the treatment of heavy menstrual bleeding, the response rate was higher in the COC group than the placebo group (42 versus 3 percent; odds ratio [OR] 22, 95% CI 4-111) [16].
Close follow-up is essential until the patient is taking only one pill per day. The patient should be instructed to call if bleeding is not well controlled.
We recommend that patients and caregivers receive written instructions detailing the steps of the taper that they can refer to as needed. We include instructions on when to go to the emergency department (eg, fainting, shortness of breath, light-headedness) and how to contact the office (with phone numbers) during clinic hours and after hours.
If bleeding recurs during the taper, we temporarily increase the total daily dose of hormone (ie, number of pills per day) to the lowest dose that controls bleeding.
High-dose estrogen therapy often causes nausea, which may result in decreased adherence [2]. If nausea occurs, we prescribe either ondansetron 4 to 8 mg orally or promethazine 12.5 to 25 mg orally or per rectum. The antiemetic should be taken one hour before each dose of hormone.
Alternatives
●Oral progestin-only therapy – Oral progestin-only therapy is an alternative for patients in whom estrogen is contraindicated (eg, migraine with aura, systemic lupus erythematosus with positive or unknown antiphospholipid antibodies, arterial or venous thromboembolic disease, estrogen-dependent tumors, and hepatic dysfunction or disease) [14,15,19,26] or who experience severe nausea with COC pills. We counsel patients that cyclic oral progestin-only regimens do not provide contraception. If these patients are also unable to swallow pills or desire contraception, depot medroxyprogesterone may be tried or the 52 mg levonorgestrel (LNG) intrauterine device (IUD) may be placed.
Among the oral progestin-only alternatives (table 4), we prefer norethindrone acetate to treat acute heavy bleeding because it provides enough estrogenic activity to minimize breakthrough bleeding but not enough to stimulate endometrial bleeding.
The norethindrone dose required to control bleeding ranges from 5 to 10 mg, and it can be administered up to four times per day.
Once bleeding subsides, the number of tablets can be tapered over several days. The same strength of pill that was required to control the bleeding is used for the taper. Two commonly used tapering regimens are provided below [13,15]:
•One tablet twice per day for seven days, followed by one tablet daily until maintenance therapy is initiated (see 'Maintenance therapy once bleeding is controlled' below)
•One tablet three times per day for three days, followed by one tablet twice per day for seven days, followed by one tablet daily until maintenance therapy is initiated (see 'Maintenance therapy once bleeding is controlled' below)
●52 mg LNG IUD – The 52 mg LNG IUD provides both contraception and stabilization of heavy uterine bleeding. Many gynecologists, family medicine providers, and adolescent medicine providers offer the 52 mg LNG IUD as first-line management for acute bleeding. However, few pediatric offices have providers who can perform same-day IUD placement. (See "Contraception: Overview of issues specific to adolescents", section on 'Long-acting reversible methods'.)
In observational studies, the 52 mg LNG IUD was associated with a reduction in menstrual bleeding and resolution of anemia among adolescents with heavy menstrual bleeding and bleeding disorders [28-30]. In an electronic survey of providers, almost all of the 312 respondents considered an LNG IUD to be safe and effective for adolescents with heavy menstrual bleeding [31].
●IV estrogen – IV conjugated estrogen therapy is reserved for patients with severe anovulatory uterine bleeding who are unstable and cannot take oral medications or whose heavy bleeding continues after 24 hours of oral estrogen-progestin combination therapy [18]. (See "Managing an episode of acute uterine bleeding", section on 'Alternative: High-dose intravenous estrogen'.)
We administer 25 mg of IV conjugated estrogen every 4 to 6 hours for 24 hours. Bleeding usually subsides within 4 to 24 hours of initiating IV estrogen [26]. Thromboembolism is a potential complication [32], and no more than six doses should be administered. (See 'Venous thromboembolism risk' above and "Combined estrogen-progestin contraception: Side effects and health concerns".)
Antiemetic therapy (eg, promethazine 12.5 to 25 mg orally, IV, or per rectum) may be required due to the high dose of estrogen used. A dose of antiemetic one hour before each dose of IV estrogen may alleviate the side effects of nausea and vomiting.
Once bleeding subsides, we begin a dose taper using an oral combination monophasic contraceptive pill that contains 30 to 35 mcg of estradiol, as follows (table 3):
•One pill every four to six hours for four days, then
•One pill every eight hours for three days, then
•One pill every 12 hours for two weeks, then
•One pill once per day until initiation of maintenance therapy (see 'Maintenance therapy once bleeding is controlled' below)
Multiple alternative tapering regimens are described in the literature [2,18-20].
The hormonally active pills are taken continuously to avoid withdrawal menses, and we instruct the adolescent to discard the pills that do not contain hormone (ie, placebo pills).
Close follow-up is essential until the patient is taking only one pill per day.
We recommend that patients and caregivers receive written instructions detailing the steps of the taper that they can refer to as needed. We include instructions on when to go to the emergency department (eg, fainting, shortness of breath, light-headedness) and how to contact the office (with phone numbers) during clinic hours and after hours.
If bleeding recurs during the taper, we temporarily increase the total daily dose of hormone (ie, number of pills per day) to the lowest dose that controls bleeding.
Antiemetic therapy may need to be continued while patients are taking more than one pill per day. Provided that hemostasis is maintained, the treatment regimen may be altered as necessary to prevent or minimize the side effects of high-dose estrogen.
Inadequate response to IV estrogen therapy or presence of platelet dysfunction — We add hemostatic therapy when severe anovulatory uterine bleeding does not improve after 24 hours of IV estrogen therapy or when patients have platelet dysfunction [33]. We also add oral progestin to stabilize the endometrium (table 4). Oral progestin should be discontinued when the transition to oral contraceptive pills occurs [2,34].
Hemostatic therapies include tranexamic acid (TXA) and aminocaproic acid [27,35-39]. We prefer TXA unless the patient has increased risks for thromboembolism [40]. (See "Managing an episode of acute uterine bleeding", section on 'Tranexamic acid'.)
●TXA is administered orally: 1300 mg three times per day for up to five days
●Aminocaproic acid may be administered orally or IV as follows:
•Aminocaproic acid 5 g orally during the first hour, followed by a continuous dose of 1 to 1.25 g per hour; treatment is continued for approximately eight hours or until the bleeding has been controlled, or
•Aminocaproic acid 4 to 5 g IV during the first hour of treatment, followed by a continuous infusion at a rate of 1 g per hour; treatment is continued for approximately eight hours or until the bleeding has been controlled
Aminocaproic acid should not be used in patients with kidney function impairment.
A hematology consult is advised for patients with an inadequate response to IV estrogen because these patients are more likely to have an underlying bleeding disorder.
Management of refractory uterine bleeding — In the rare cases in which treatment with hormones and antifibrinolytics agents fail, additional evaluation (eg, examination under anesthesia, endometrial sampling, pelvic ultrasound) may be necessary to evaluate for other causes of abnormal uterine bleeding. In particular, the presence of clots within the uterus may hamper uterine contractions and require evacuation.
Suction curettage/dilation and curettage (D&C) may be used as a therapeutic intervention. However, a therapeutic D&C procedure is rarely required in adolescents with anovulatory uterine bleeding. It should be reserved as a last resort for the rare patient who continues to have life-threatening bleeding despite other therapies [41]. If a D&C is performed in an adolescent, care must be taken to prevent scarring of the endometrial lining (Asherman syndrome). Thus, suction curettage is preferred to sharp curettage. (See "Intrauterine adhesions: Clinical manifestation and diagnosis", section on 'Etiology and risk factors' and "Dilation and curettage", section on 'Indications'.)
These patients should also have a hematology consult to evaluate for an underlying bleeding disorder.
Maintenance therapy once bleeding is controlled — Once the acute episode of anovulatory bleeding is controlled and the initial course of hormonal therapy is complete, management decisions depend upon:
●Initial hormonal regimen
●Status of anemia
●Patient's desire for contraception
We advise all patients to use a paper menstrual calendar (figure 2) or one of several freely available smart phone applications (apps) [9,12] to monitor subsequent episodes of anovulatory uterine bleeding. A menstrual calendar may also serve as a reminder of when to take hormonal medication (or schedule an injection).
We schedule follow-up visits monthly until menstrual patterns and hormonal treatments are stable and hemoglobin is >10 g/dL. For patients who require hospitalization, we schedule the first follow-up visit two weeks after discharge.
The maintenance regimen is determined based on the regimen that was chosen to stabilize the patient's acute bleeding.
●Bleeding controlled with estrogen-containing method – For patients with anovulatory uterine bleeding that was initially controlled with an estrogen-containing regimen (IV or oral), our suggested oral contraceptive regimens below are determined by the severity of anemia.
•Hemoglobin <10 g/dL – For patients whose hemoglobin remains <10 g/dL, we continue daily monophasic COCs with 30 to 35 mcg of ethinyl estradiol (table 3) until hemoglobin (monitored monthly) is ≥10 g/dL [2,11,18].
The hormonally active pills are taken continuously to avoid withdrawal menses. During continuous oral contraceptive therapy, it may be helpful to prescribe 21-day packages or to remove the placebo (hormone-free) pills from 28-day packages so the adolescent does not inadvertently take hormone-free pills [11].
We counsel patients that breakthrough bleeding is common during the first three months of continuous hormonal therapy and possibly for longer. If breakthrough bleeding is very heavy or lasts more than 10 to 14 days, we advise patients to resume twice-daily dosing. We advise them to continue the higher dose for two weeks (without use of hormone-free pills) and then attempt another taper to daily dosing.
Breakthrough bleeding may be caused by an excessively proliferated endometrium. Therefore, in hemodynamically stable patients, some clinicians discontinue hormones for at least three days to permit shedding of the endometrium. This may lead to very heavy bleeding; however, once the oral contraceptive pill is restarted, the bleeding should subside.
•Hemoglobin ≥10 g/dL – Once hemoglobin is ≥10 g/dL or for patients whose hemoglobin is ≥10 g/dL at the start of maintenance therapy, we first pause hormonal pills for seven days to induce a withdrawal bleed. This allows endometrial shedding of what may be a dyssynchronous proliferated endometrium. Cyclic bleeding is then established with monophasic COCs containing at least 30 mcg of ethinyl estradiol for six months.
When the adolescent begins cyclic therapy, we counsel that withdrawal bleeding typically begins two to four days after the last hormone-containing pills are taken. Although menstrual flow during the initial withdrawal period may be heavier than normal, it should not last longer than seven days [2,11].
The use of contraceptive patches or vaginal rings is also an acceptable approach in patients who prefer a nondaily contraceptive option.
We monitor hemoglobin every three to six months until it is >12 g/dL. Once anemia has resolved, use of COCs, patches, or rings can be discontinued after six months to determine whether a normal menstrual pattern has been established [42]. However, it is medically appropriate to continue hormonal therapy if an adolescent chooses to do so for contraception or ongoing cycle predictability.
If bleeding becomes severe or prolonged again, patients should be seen acutely. Once the patient is stable, we schedule annual follow-up visits.
●Bleeding controlled with progestin-only pills – For patients with anovulatory uterine bleeding that was initially controlled with progestin-only pills, our suggested progestin-only regimens are determined by the severity of anemia.
•Hemoglobin <10 g/dL – For patients whose hemoglobin remains <10 g/dL, we monitor hemoglobin monthly and continue norethindrone acetate 5 to 10 mg daily.
•Hemoglobin ≥10 g/dL – Once hemoglobin is ≥10 g/dL or for patients whose hemoglobin is ≥10 g/dL at the start of maintenance therapy, we first pause hormonal pills for seven days to induce a withdrawal bleed. This allows for endometrial shedding of what may be a dyssynchronous proliferated endometrium.
If the withdrawal bleed is heavy or prolonged, we ask the patient to contact us to schedule an urgent follow-up visit.
Once endometrial shedding has occurred, we transition patients to cyclic maintenance therapy or a daily progestin-only contraceptive for at least six months (table 4). A quarterly contraceptive injection is a reasonable alternative, as is a long-acting reversible contraceptive (LARC). (See "Contraception: Overview of issues specific to adolescents", section on 'Long-acting reversible methods'.)
Daily oral progestin-only options with contraceptive efficacy include:
-Norethindrone 0.35 mg once daily; effective for contraception when taken consistently
-Drospirenone 4 mg once daily for 24 days followed by inactive pill once daily for four days
Cyclic oral progestin-only options (no proven contraceptive efficacy) include:
-Norethindrone acetate 5 mg daily for the first 5 to 10 days of each calendar month
-Micronized progesterone 200 mg daily for the first 12 days of each calendar month
-Medroxyprogesterone acetate 10 mg orally for the first 10 days of each calendar month
Scheduling pills to start on the first day of each calendar month is easier for the patient to remember than using an every-four-week schedule.
We advise patients that bleeding associated with cyclic progestins usually begins two to three days after the last dose but may be delayed for up to one week. If bleeding begins while the patient is taking maintenance progestin, we advise them to discontinue the remaining doses for that month, allow menses to occur, and then resume hormonal therapy.
We counsel adolescents that cyclic oral progestins are not methods of contraception. If they desire contraception, they will need to change their hormonal therapy to a method that controls anovulatory bleeding and prevents pregnancy. If they have unprotected sexual intercourse while using progestin-only therapy, emergency contraception should be offered. (See "Contraception: Counseling and selection" and "Emergency contraception" and "Contraception: Overview of issues specific to adolescents", section on 'Factors to consider'.)
We schedule follow-up visits every three to six months. After 6 to 12 months of cycle control, hormonal therapy can be discontinued to determine whether a normal menstrual pattern has been established [42]. However, it is medically appropriate to continue hormonal therapy if an adolescent chooses to do so for contraception or ongoing cycle predictability.
If bleeding becomes severe or prolonged again, patients should be seen acutely. Once stable, patients should receive annual follow-up visits. (See 'Long-term monitoring' below.)
●Long-acting progestin-only options that provide contraception – For patients who do not want to take a daily pill, are unable to take pills effectively, or cannot use estrogen but desire contraception, the 52 mg LNG-releasing IUD may be preferred and can be placed at any time [25,43]. Additionally, the etonogestrel implant can be placed once the acute phase of bleeding has been stabilized. As with most progestin-only hormonal contraceptives, these longer-acting methods may be associated with unpredictable bleeding for up to six months and sometimes longer.
The LNG IUD and etonogestrel implant provide effective LARC (failure rates <1 percent).The use of these methods is discussed separately. (See "Intrauterine contraception: Background and device types", section on 'Levonorgestrel IUDs' and "Contraception: Etonogestrel implant", section on 'Side effects' and "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration", section on 'Adolescents'.)
LONG-TERM MONITORING —
Long-term monitoring and follow-up are necessary to prevent the potential sequelae of anovulatory uterine bleeding (eg, chronic anemia, endometrial cancer). If hormonal therapy is discontinued after establishing regular menstrual cycles and periods occur at intervals greater than three months (and pregnancy test is negative), patients should undergo an endocrine evaluation to rule out other causes of anovulation (including polycystic ovary syndrome) and receive progesterone to induce withdrawal bleeding [34].
●Endocrine evaluation – The endocrine evaluation typically includes early-morning (7 to 9 AM) follicle-stimulating hormone, luteinizing hormone, prolactin, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, total testosterone, and thyroid-stimulating hormone to evaluate for potential disorders of the hypothalamic-pituitary-ovarian (HPO) axis and polycystic ovary syndrome. (See "Abnormal uterine bleeding in adolescents: Evaluation and approach to diagnosis".)
●Induction of withdrawal bleeding – To induce withdrawal bleeding, we use oral micronized progesterone 200 mg nightly for 12 days per month.
Alternative regimens include medroxyprogesterone 10 mg nightly for 10 days per month and norethindrone acetate 5 mg nightly for 5 to 10 days per month.
We instruct the adolescent to induce menses at least every three months or to restart combined hormonal contraception [34].
●Prevention of endometrial hyperplasia – Chronic anovulation (greater than two to three years in duration) is associated with endometrial hyperplasia and increased risk for endometrial carcinoma [44]. Body mass index (BMI) ≥30 kg/m2 promotes peripheral conversion of androgens to estrogens, further enhancing endometrial growth.
Endometrial biopsy may be warranted in adolescents who have a history of two to three years of untreated anovulatory bleeding, particularly if they have a BMI ≥30 kg/m2 or have a family history of endometrial, ovarian, breast, or colon cancer [18]. (See "Endometrial carcinoma: Epidemiology, risk factors, and prevention", section on 'Risk factors'.)
PROGNOSIS —
Anovulatory uterine bleeding generally resolves with maturation of the hypothalamic-pituitary-ovarian (HPO) axis. The duration of time that it takes the HPO axis to attain maturity (regular, ovulatory cycles) varies depending on age at menarche. Following the first menses, 50 percent of cycles are ovulatory by [45]:
●One year when menarche occurs at <12 years of age
●Three years when menarche occurs between 12 and 13 years of age
●Four and a half years when menarche occurs at >13 years of age
Patients with a long history of anovulatory cycles and anovulatory uterine bleeding, particularly those with polycystic ovary syndrome, have an increased risk of later infertility and endometrial carcinoma [46]. (See "Female infertility: Causes", section on 'Ovulatory disorders' and "Endometrial carcinoma: Epidemiology, risk factors, and prevention", section on 'Risk factors'.)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Abnormal uterine bleeding".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)
●Basics topics (see "Patient education: Absent or irregular periods (The Basics)" and "Patient education: Heavy periods (The Basics)")
●Beyond the Basics topics (see "Patient education: Absent or irregular periods (Beyond the Basics)" and "Patient education: Abnormal uterine bleeding (Beyond the Basics)" and "Patient education: Heavy periods (Beyond the Basics)")
PATIENT PERSPECTIVE TOPIC —
Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: von Willebrand disease".)
SUMMARY AND RECOMMENDATIONS
●Terminology and etiology – Anovulatory uterine bleeding is characterized by noncyclic menstrual blood flow and is a diagnosis of exclusion. Noncyclic menstrual blood flow occurs when sex steroid production is not synchronized. Immaturity of the hypothalamic-pituitary-ovarian (HPO) axis is the most common cause of anovulatory uterine bleeding in adolescents (figure 1). (See 'Introduction' above.)
●Pretreatment evaluation – It is important to exclude pregnancy and pelvic infection before initiating treatment for anovulatory uterine bleeding. If not already assessed, an evaluation for other causes of abnormal uterine bleeding should be conducted (table 1). (See 'Pretreatment evaluation' above and "Abnormal uterine bleeding in adolescents: Evaluation and approach to diagnosis", section on 'Approach to diagnosis'.)
●Management of mild to moderate anovulatory uterine bleeding – The acute management of mild to moderate anovulatory uterine bleeding depends upon bleeding severity, patient and caregiver preferences, and desire for contraception:
•Mild bleeding – Mild anovulatory uterine bleeding is characterized by slightly or moderately increased menstrual flow and longer-than-normal menses or shortened cycles for more than two months. Hemoglobin is usually normal (≥12 g/dL) but may be mildly decreased (10 to 12 g/dL). (See 'Bleeding severity classification' above.)
Most patients with mild bleeding do not require treatment and can be managed with observation unless they desire contraception or menstrual regulation. (See 'Mild bleeding' above.)
•Moderate bleeding – Moderate anovulatory uterine bleeding is characterized by moderately or severely increased menstrual flow and prolonged or frequent menses occurring every one to three weeks. Hemoglobin is usually ≥10 g/dL and <12 g/dL. (See 'Bleeding severity classification' above and 'Moderate bleeding' above.)
-In patients with moderate anovulatory uterine bleeding who are not actively bleeding, we suggest either combined estrogen-progestin oral contraceptives or progestin-only hormone therapy rather than an intrauterine device (IUD) or other agents for initial management (Grade 2C).
-In patients with moderate anovulatory uterine bleeding who are actively bleeding, we suggest combined estrogen-progestin oral contraceptives rather than progestin-only therapy or other options for initial management (Grade 2C). A combined estrogen-progestin method is preferred because the estrogen component may provide better hemostasis.
Progestin-only options are acceptable alternatives for patients who have a contraindication to estrogen use.
●Management of severe bleeding – Severe anovulatory uterine bleeding is characterized by prolonged, heavy menstrual flow that may or may not cause hemodynamic instability. Hemoglobin is usually <10 g/dL. (See 'Bleeding severity classification' above and 'Management of severe anovulatory uterine bleeding' above.)
•Indications for hospitalization in patients with severe anovulatory uterine bleeding include hemodynamic instability, hemoglobin concentration <7 g/dL or <10 g/dL with active heavy bleeding, symptomatic anemia, need for intravenous (IV) conjugated estrogen, or need for surgical intervention. (See 'Indications for hospitalization' above.)
•In patients with severe anovulatory uterine bleeding, we suggest combined estrogen-progestin with 30 to 35 mcg of ethinyl estradiol as the initial intervention rather than other medical therapies or surgery (Grade 2C). Hormonal therapy generally suppresses severe bleeding rapidly enough that hemostatic agents and/or surgical intervention, which carry higher risk, are not required. (See 'Hormonal therapy' above.)
Oral progestin-only and IV estrogen are reasonable alternatives. (See 'Alternatives' above.)
●Anemia – Anemia is common in patients with anovulatory uterine bleeding and should be treated with iron supplementation. (See "Iron requirements and iron deficiency in adolescents".)
●Long-term monitoring – Long-term monitoring and follow-up are necessary to prevent the potential sequelae of untreated anovulatory uterine bleeding (eg, chronic anemia, endometrial cancer). If hormonal therapy is discontinued after establishing regular menstrual cycles, it can be restarted if anovulatory uterine bleeding recurs.
If hormonal therapy is discontinued and menses occur at intervals greater than three months (and pregnancy test is negative), patients should undergo an endocrine evaluation and receive a course of progestin to induce withdrawal bleeding. (See 'Long-term monitoring' above.)
ACKNOWLEDGMENT —
The editorial staff at UpToDate, Inc. acknowledges Dr. Robert Zurawin, who contributed to an earlier version of this topic review.
