Medical Care:
Oral contraceptives
Oral contraceptive pills (OCPs) suppress endometrial development, reestablish predictable bleeding patterns, decrease menstrual flow, and lower the risk of iron deficiency anemia.
Acute episodes of heavy bleeding suggest an environment of prolonged estrogenic exposure and buildup of the lining.
Bleeding usually is controlled within the first 24 hours, as the overgrown endometrium becomes pseudodecidualized. Seek alternate diagnosis if flow fails to abate in 24 hours.
Estrogen
Estrogen alone, in high doses, is indicated in certain clinical situations.
Prolonged uterine bleeding suggests the epithelial lining of the cavity has become denuded over time. In this setting, a progestin is unlikely to control bleeding. Estrogen alone will induce return to normal endometrial growth rapidly.
Hemorrhagic uterine bleeding requires high-dose estrogen therapy. If bleeding is not controlled within 12-24 hours, a D&C is indicated.
Beginning progestin therapy shortly after initiating estrogen therapy to prevent a subsequent bleeding episode from treatment with prolonged unopposed estrogen is wise.
Progestins
Chronic management of DUB requires episodic or continuous exposure to a progestin. In patients without contraindications, this is best accomplished with an oral contraceptive given the many additional benefits, including decreased dysmenorrhea, decreased blood loss, ovarian cancer prophylaxis, and decreased androgens.
In patients with a pill contraindication, cyclic progestin for 12 days per month using medroxyprogesterone acetate (10 mg/d) or norethindrone acetate (2.5-5 mg/d) provides predictable uterine withdrawal bleeding, but not contraception. Cyclic natural progesterone (200 mg/d) may be used in women susceptible to pregnancy, but may cause more drowsiness and does not decrease blood loss as much as a progestin.
In women who are unable to tolerate systemic progestins/progesterone, a progestin secreting IUD may be considered that controls the endometrium via a local release of levonorgestrel, avoiding systemic levels.
On rare occasions, a young patient with anovulatory bleeding also might have a bleeding disorder. Desmopressin, a synthetic analog of arginine vasopressin, has been used as a last resort to treat abnormal uterine bleeding in patients with documented coagulation disorders. Treatment is followed by a rapid increase in von Willebrand factor and factor VIII, which lasts about 6 hours.
Surgical Care: Most cases of DUB can be treated medically. Surgical measures are reserved for situations when medical therapy has failed or is contraindicated.
D&C is an appropriate diagnostic step in a patient who fails to respond to hormonal management.
The addition of hysteroscopy will aid in the treatment of endometrial polyps or the performance of directed uterine biopsies.
As a rule, apply D&C rarely for therapeutic use in DUB because it has not been shown to be very efficacious.
Abdominal or vaginal hysterectomy might be necessary in patients who have failed or declined hormonal therapy, have symptomatic anemia, and who experience a disruption in their quality of life from persistent, unscheduled bleeding.
Endometrial ablation is an alternative for those who wish to avoid hysterectomy or who are not candidates for major surgery.
Ablation techniques are varied and can employ laser, rollerball, resectoscope, or thermal destructive modalities. Most of these procedures are associated with high patient satisfaction rates.
Pretreat the patient with an agent, such as leuprolide acetate, medroxyprogesterone acetate, or danazol, to thin the endometrium.
The ablation procedure is more conservative than hysterectomy and has a shorter recovery time.
Some patients may have persistent bleeding and require repeat procedures or move on to hysterectomy. Rebleeding following ablation has raised concern about the possibility of an occult endometrial cancer developing within a pocket of active endometrium. Few reported cases exist, but further studies are needed to quantify this risk.
Endometrial ablation is not a form of contraception. Some studies report up to a 5% pregnancy rate in postablation procedures.
DRUG TREATMENT : Estrogens, progestins, androgens, nonsteroidal anti-inflammatory drugs (NSAIDs), ergot derivatives, antifibrinolytics, and gonadotropin-releasing hormone (GnRH) agonists have been used to treat DUB. 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 DUB 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 e-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.
1. OESTROGENS -- 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 DUB 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 )
2. PROGESTINS : 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
3. COMBINATION ORAL CONTRACEPTIVES : Contraceptive pills containing estrogen and progestin have been advocated for nonsmoking patients with DUB 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 DUB, combination oral contraceptives are very effective
- ETHINYL ESTRADIOL & PROGESTIN DERIVATIVE ( OVRAL, ORTHO-NOVUM )
4. NSAIDS : 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 DUB.
- NAPROXEN
5. GONADOTROPIN RELEASING HORMONE AGONISTS : 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, 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
6. ARGININE VASOPRESSIN DERIVATIVES : INDICATED IN PATIENTS WITH THROMBOEMBOLIC DISORDERS.
- DESMOPRESSIN ACETATE - Has been used to treat abnormal uterine bleeding in patients with coagulation defects. Transiently elevates factor VIII and von Willebrand factor.
ALTERNATIVE DRUGS :
. Progesterone:
. 100 mg IM progesterone in oil (an alternate to oral medroxyprogesterone). This works well for active bleeding. Not appropriate for cyclic therapy.
. Vaginal suppositories due to leakage and uncertain amount of effective medication should not be used
. Natural progesterone lozenges (sublingual/oral) have not be adequately studied for use with DUB and
have questionable safety.
. Danazol (Danocrine) [unlabeled use]: 200-400 mg/day. Much more expensive and may cause masculinization. Usually reserved for women planning to undergo endometrial ablation soon.
PATIENT MONITORING : All women treated for DUB with estrogens should maintain a menstrual calendar to document the pattern of bleeding abnormalities and their relation to therapy
POSSIBLE COMPLICATIONS :
β’ Anemia
β’ Adenocarcinoma of the uterus if prolonged unopposed estrogen stimulation in women with intact uterus
β’ Significant side effects of individual preparations.
EXPECTED COURSE/PROGNOSIS :
β’ Varies with pathophysiologic process
β’ In young women, most anovulatory cycles can be treated confi dently and successfully with physiologically
sound therapeutic regimens, without surgical intervention