Once a diagnosis of either anovulatory or ovulatory dysfunctional uterine bleeding is made, either tentatively or more definitively, treatment is tailored to the individual circumstances of the case. These include a host of factors, including the degree of ongoing bleeding and the presence or absence of hemodynamic stability, whether or not causes of bleeding other than dysfunctional uterine bleeding are also present, and future fertility considerations. The focus of the treatment modalities discussed here is those for dysfunctional uterine bleeding, but many of these same modalities may be indicated for other causes of abnormal bleeding. For example, many of the treatments effective in cases of ovulatory dysfunctional uterine bleeding can also be applied successfully in cases of VWD.
For women with apparent anovulatory dysfunctional uterine bleeding, following initial diagnostic measures, the first goal of therapy is to stop the acute bleeding episode. This can nearly always be accomplished without surgical intervention. If uterine curettage is performed, this by itself does provide a substantial acute therapeutic effect, although in general there is no reason not to start medical therapy immediately after endometrial sampling of any kind. In most cases of anovulatory dysfunctional uterine bleeding, the bleeding can be stopped with the administration of a progestin. A typical progestin regimen is medroxyprogesterone acetate (MPA), 10-20 mg orally once daily for 10 days. This will usually stop the bleeding during the time it is being administered followed by more or less orderly withdrawal bleeding starting immediately after the MPA is discontinued. This sequence of events is similar to that of the secretory phase of the normal cycle. It is important to advise the patient at risk for pregnancy that occasionally ovulation will occur as a result of progestin administration and that she should expect to have bleeding after it has been stopped.
Another therapeutic option useful in stopping acute anovulatory dysfunctional uterine bleeding involves oral contraceptives (oral contraceptives), each containing 30-35 µg of ethinyl estradiol and a progestin. A variety of regimens may be used, including, for example, having the patient take 2-4 pills daily for five days, which will often bring the bleeding to a halt within one or two days, followed by another 21 days of one pill daily, after which withdrawal bleeding can be expected. For the patient who has been bleeding heavily for a prolonged period of time, with little residual endometrial tissue, it may be best to initially use high-dose estrogen therapy, for example conjugated estrogens (Premarin), 25 mg by intravenous bolus every 4 hours for two or three doses. The immediate improvement with such therapy is due more to a pharmacologic effect of estrogen on small vessel hemostasis than to estrogen’s ability to cause proliferation and healing of endometrial tissue. Once the bleeding has stopped in response to such treatment, in general an oral contraceptive regimen should be started.
Patients diagnosed as having anovulatory dysfunctional uterine bleeding, but not responsive to the regimens outlined above, require additional evaluation. This may include endometrial sampling if not previously performed, SSH, or hysteroscopy.
Once the acute episode of anovulatory dysfunctional uterine bleeding has been treated, attention is directed towards the possible need for long-term treatment. For the patient who is usually ovulatory, for whom it is thought that the bleeding episode just treated is unlikely to recur, a period of observation may be all that is necessary. On the other hand, some form of chronic therapy is indicated for patients whose anovulatory state responsible for the dysfunctional uterine bleeding is unlikely to abate spontaneously. The goals of this long-term therapy, which must include a progestin component, are to prevent recurrences of the unpredictable bleeding episodes, prevent endometrial hyperplasia, and lower the patient’s risk for endometrial cancer. Iron supplementation should be started at this time, if indicated.
Long-term treatment with oral contraceptives in the usual cyclic fashion is the best treatment for most patients with anovulatory dysfunctional uterine bleeding, although some patients may prefer extended-cycle oral contraceptives. Treatment with oral contraceptives is particularly useful for those women who occasionally undergo spontaneous ovulation and need birth control, as well as those with polycystic ovarian syndrome, because of amelioration of the associated hyperandrogenism. Patients who are not candidates for oral contraceptive use may be treated with cyclic progestin treatment, for example, MPA, 10 mg orally once daily the first 10-14 days of each month, or even every second or third month. Anovulatory women with dysfunctional uterine bleeding who desire pregnancy should of course have an appropriate hormonal evaluation followed by initiation of ovulation induction therapy.
Patients diagnosed as having ovulatory dysfunctional uterine bleeding can be treated successfully with several different regimens, both hormonal and nonhormonal in nature. These include oral contraceptives or a nonsteroidal anti-inflammatory drug (NSAID) regimen, such as ibuprofen, 400 mg orally every 6 hours, starting on cycle day 1 and continuing through cessation of menses. Both of these treatments not only decrease the amount of bleeding, but also address the often associated problem of dysmenorrhea. The mechanism by which NSAIDs work is not entirely clear, but appears to involve a disproportionate reduction in the uterine concentrations of vasodilatory prostaglandins as compared to that of the prostaglandin F2alpha, a potent vasoconstrictor.
Another possible treatment modality for ovulatory dysfunctional uterine bleeding is an antifibrinolytic agent, such as epsilon aminocaproic acid. In particular, there is strong evidence that the antifibrinolytic agent tranexamic acid is very effective, but unfortunately this agent is not generally available in the United States. Still another option is danazol, for example, 200 mg orally daily. Most patients taking such a dose continue to experience regular menses, and androgenic side effects may be a problem. Furthermore, barrier contraception is needed if the patient is sexually active.
An option for ovulatory dysfunctional uterine bleeding that may be underutilized in the United States is the Mirena levonorgestrel-releasing intrauterine system (levonorgestrel intrauterine system). The levonorgestrel intrauterine system is an intrauterine device designed to release 20 µg of the progestin levonorgestrel daily over a period of 5 years. Although only approved in this country as a birth control measure, many studies have shown the levonorgestrel intrauterine system to be highly effectively for ovulatory dysfunctional uterine bleeding, with large reductions (greater than 80%) of blood loss, and overall outcomes comparable to those achieved with endometrial ablation. The effects seen are primarily on the basis of local endometrial effects, as a substantial majority of ovulatory women using the levonorgestrel intrauterine system continue to ovulate regularly. Interestingly, despite continued ovulation, women with endometriosis and ovulatory dysfunctional uterine bleeding have reduced dysmenorrhea symptoms after levonorgestrel intrauterine system insertion. Furthermore, women with abnormal bleeding attributed to myomas also experience decreased bleeding after levonorgestrel intrauterine system insertion, and the device provides effective treatment for endome-trial hyperplasia. For women with ovulatory dysfunctional uterine bleeding, the most common side effect is breakthrough bleeding, and there is an increased risk of functional cyst formation.
At times, patients with either anovulatory or ovulatory dysfunctional uterine bleeding have a consistently poor response to the long-term medical options described, or unacceptable side effects. In that situation, consideration may be given to treatment with a long-acting gonadotropin releasing hormone (GnRH) agonist, such as leuprolide acetate, to induce a menopause-like state. Long-term treatment with a gonadotropin releasing hormone agonist for most patients is problematic, however, because of the adverse effects on bone density as well as vasomotor symptoms. Thus in general, a patient with dysfunctional uterine bleeding failing to respond to the regimens described is best treated surgically, particularly if the patient is older and future fertility is not a concern.
Long-term surgical options for dysfunctional uterine bleeding include hysterectomy and endometrial ablation. Both can be performed using several different approaches. Hysterectomy is clearly the most definitive treatment for dysfunctional uterine bleeding and can be done by laparotomy, laparoscopically, or vaginally, with the best approach for a given patient determined by the individual circumstances involved. The ovaries may be preserved. In general, hysterectomy is associated with more complications than ablation procedures but also higher long-term patient satisfaction rates and substantially lower rates of the need for repeat surgery. Furthermore women at increased risk for endometrial hyperplasia or adenocarcinoma are not good candidates for ablation.
For many patients, however, despite the advantages of hysterectomy, endometrial ablation may be a better choice, particularly if the goal is not amenorrhea. This may be because of medical reasons, such as surgical risks for hysterectomy, or personal preference, such as the desire to avoid a more major surgery. Generally about 40% of women experience amenorrhea after ablation, and a similar proportion experience significantly reduced bleeding. There are now many options available for ablation, both hysteroscopic and nonhysteroscopic, as recently reviewed by Shirk. If a nonhysteroscopic approach is used, in general a diagnostic hysteroscopy should be done beforehand. This primarily has to do with not missing lesions such as carcinomas or submucosal myomas.