What is Anovulatory Bleeding (Abnormal Uterine Bleeding)?
When a woman experiences unpredictable, extended, and often heavy menstrual bleeding, it could be due to a condition known as abnormal uterine bleeding associated with ovulatory dysfunction or anovulatory bleeding. This condition can cause irregular menstrual cycles and is common among young girls just starting their periods and older women nearing menopause. However, it can happen at any age during women’s reproductive years.
This condition is one of the main reasons for abnormal uterine bleeding, a problem that affects up to a third of women who are of childbearing age. It’s often the major concern discussed at doctor’s appointments. It’s important to rule out other structural and physiological causes of abnormal bleeding with medical exams, lab tests, or imaging before determining that anovulatory bleeding is the cause.
What Causes Anovulatory Bleeding (Abnormal Uterine Bleeding)?
Abnormal uterine bleeding during ovulation (AUB-O) is thought to be caused by an imbalance in the body’s hormonal system, particularly in the connections between the brain and the ovaries. It often happens when people begin their reproductive life, as the hormonal system is not yet fully matured. It can also happen near menopause because the process of egg maturation can happen too early, increasing estrogen levels and leading to heavier periods. Abnormal uterine bleeding can also occur during breastfeeding.
A medical condition, such as polycystic ovarian syndrome (PCOS), can also cause AUB-O. Other related factors include changes in body weight, emotional stress, heavy exercise, and medicines that affect the body’s dopamine metabolism, a chemical involved in sending signals in the brain.
Here are some common reasons for lack of ovulation (anovulation):
* High level of male hormones (such as with PCOS, certain adrenal gland disorders, or when a tumor is producing these hormones).
* High levels of prolactin, the hormone that helps women produce milk.
* Extreme weight-loss from disorders like anorexia.
* Strenuous exercise.
* Stress.
* Disorders of the thyroid gland.
* Pituitary gland disorders (the pituitary is a small gland at the base of the brain).
* Early ovarian failure.
* Medications.
Certain drugs, especially ones used to treat epilepsy like valproate and lamotrigine, and antipsychotic medicines, may contribute to problems with ovulation. It’s worth noting that traditional antipsychotic drugs are more likely than modern ones to cause high prolactin levels and consequent AUB-O.
Risk Factors and Frequency for Anovulatory Bleeding (Abnormal Uterine Bleeding)
Abnormal uterine bleeding, or AUB, is a common issue among women. In the United States, a study reported that 53 out of every 1,000 women of reproductive age experience AUB each year. AUB that is caused by a lack of ovulation, known as AUB-O, can happen at any point in a woman’s reproductive life. After a woman starts having regular periods, AUB-O becomes the main cause of AUB. Depending on the diagnostic criteria used in a study, between 3.4% to 18.6% of women who are menstruating were found to have anovulation, or a lack of ovulation.
It is most common in the following groups:
- Women around the time they start having periods
- Women around the time they stop having periods
- Obese women, as obesity may be a risk factor for lack of ovulation
- Women with a very low body mass index (BMI), such as those with anorexia or athletes who don’t consume enough energy for the amount they use in their sport
Signs and Symptoms of Anovulatory Bleeding (Abnormal Uterine Bleeding)
When diagnosing Abnormal Uterine Bleeding (AUB), detailed conversations about symptoms and physical exams can narrow down potential causes and help decide on the correct tests. For teenage patients, it’s important to talk both with and without the parents present, as the patient may be more honest about their symptoms and sexual behavior when their parents aren’t there. AUB often includes periods of not menstruating for months, followed by heavy bleeding or spotting, while typical premenstrual symptoms might not be present. Women at extreme ages of their reproductive years, who experience irregular bleeding, are often suspected of having AUB.
When determining a patient’s history and conducting exams, these are the key areas to consider:
- Bleeding History:
- Frequency, consistency, and length of bleeding
- The amount of blood loss, assessed by questions like the frequency of changing tampons or pads, passing blood clots, the level of saturation, and needing to change sanitary protection overnight.
- Presence or absence of bleeding after sexual intercourse
- Bleeding with stools, which can suggest a gastrointestinal issue
- Associated Symptoms: Such as fevers, chills, pelvic pain, odd vaginal discharge, and problems with bowel or bladder function
- Signs/symptoms Associated with Known Causes: For example, Polycystic Ovarian Syndrome (PCOS) can cause obesity, excessive body hair, acne; thyroid issues can cause heart palpitations, intolerance to hot/cold, fatigue, weight gain; Hyperprolactinemia can cause unexpected lactation; coagulopathy can cause easy bruising, petechiae.
- Sexual History: Including details of last intercourse, number of partners, contraception use, history of Sexually Transmitted Infections (STIs), and screening results for cervical cancer
- Medication History: Current medications including dietary supplements
- Surgical History:
- Family History: Such as the menstrual history of close relatives, history of coagulopathies, hormone-sensitive cancers.
The physical examination should focus on:
- Vital signs
- General appearance and Body Mass Index (BMI)
- Examination of eyes and mouth for signs of anemia, thyroid check
- Abdomen examination for tenderness, lumps, or swelling
- Pelvic examination: checking for anomalies in the vulva, vagina, speculum exam, pap smear, and taking cervical cultures for STI if needed. A rectal exam may also be conducted if there’s a suspicion of rectal bleeding.
Testing for Anovulatory Bleeding (Abnormal Uterine Bleeding)
The first step in checking for AUB-O, abnormal bleeding in women not due to pregnancy, is a thorough examination. Depending on the person’s history or physical findings, doctors can decide to do specific tests. However, every patient should get a pregnancy test and a complete blood count (CBC). The CBC is particularly crucial if the patient is experiencing symptoms like heavy periods, breathlessness, dizziness, fatigue, or unusual cravings for non-food items as these can indicate conditions like anemia or low platelet count. For those who have recently been pregnant or had a miscarriage, measuring the level of beta-hCG hormone can help rule out certain pregnancy-related issues.
Once doctors confirm that the patient is not pregnant and does not have anemia (or the anemia has been addressed), the focus can shift to the patient’s history, physical findings, and family history to try and figure out the reason for the abnormal bleeding. Specific tests may be carried out based on these findings:
– If there’s concern about thyroid problems: A serum thyroid-stimulating hormone (TSH) test.
– If there’s concern about high prolactin levels: A serum prolactin test.
– If there’s suspicion of PCOS, a hormonal disorder: Tests for 17-OH-progesterone, total and free testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH).
– If there’s a concern about a bleeding disorder: Tests for CBC, prothrombin time (PT), partial thromboplastin time (PTT), von Willebrand factor (vWF) antigen test, factor VIII level, platelet aggregation studies.
Specific treatments can be given based on the results of these tests. If there are no unusual findings or positive tests, the medical team can start medical management.
There are also age-specific considerations. For younger patients (from puberty to 18 years), it would be quite unusual to see endometrial hyperplasia, a condition where the uterine lining becomes too thick. However, if unexplained anovulatory cycles persist for more than two years, a biopsy may be necessary. In this age group, heavy periods could indicate a bleeding disorder.
In women aged 19 to 39 years, a small percentage may have a condition called PCOS. If medical treatment doesn’t control the bleeding, doctors might carry out an endometrial biopsy.
For women aged 40 and older, an endometrial biopsy is typically done as a first test, especially if over 45, or if they have concerning personal or family histories.
In cases of acute AUB, sudden heavy bleeding that needs immediate medical attention, a doctor would first stabilize the patient. Then they would carry out a transvaginal ultrasound and a sonohysterography to check the uterus and endometrium (lining of the uterus).
Imaging, like hysteroscopy, transvaginal ultrasonography, MRI, and saline infusion sonohysterography, can be used initially if suggested by history or symptoms, or later on in patients who do not respond to initial medical treatments.
Treatment Options for Anovulatory Bleeding (Abnormal Uterine Bleeding)
In simple terms, the treatment for anovulatory abnormal uterine bleeding (AUB-O) depends on the cause of the anovulation and what the patient wants to achieve through therapy. If possible, any existing hormonal imbalances should be addressed. Treating problems like eating disorders or stress may help, though it can be hard. If medications are causing problems with ovulation, doctors should advise on the necessity of such drugs, the pros and cons of alternatives, and how to minimize the drug’s impact. The patient’s reproduction goals can heavily influence the treatment path. Over all, patient safety must always be a priority because anovulatory issues may lead to abnormal enlargement or cancer of the endometrium (lining of the uterus).
The primary treatment for AUB-O usually involves medications. These can either feature only progestin or a mixture of hormones. Progestin therapy is available in several forms including an intrauterine device, a muscle injection, and an oral pill. It can also be given non-contraceptively in a cycle to induce regular bleeding. The Levonorgestrel-releasing intrauterine device fits into treatment plans for all age groups. Combined hormonal contraceptives come in a variety of forms like pills, patches, and vaginal rings and these can all work in preventing endometrial hyperplasia or cancer. Both types may regularize patient’s bleeding if that’s preferred by the patient.
If a patient wants to conceive, contraceptives won’t help. They might be used temporarily until the patient is ready for pregnancy. Treatment of underlying disorders remains crucial. For instance, women with polycystic ovarian syndrome can lower their androgen levels by losing weight. Even a 5% body weight loss can restore normal menstruation. Certain weight loss medicines may also help improve ovarian function. In anovulatory patients aiming for pregnancy, medicines like letrozole or clomiphene citrate can initiate ovulation. Recent studies suggest that letrozole may be more effective than clomiphene in PCOS patients. Metformin, a drug that improves insulin sensitivity, can also be used in these patients, notably in overweight women, to increase pregnancy rates.
Surgical intervention for AUB-O is considered if medications don’t work or can’t be used due to medical contraindications. A procedure known as laparoscopic ovarian drilling may be an option for patients with PCOS who want to conceive but haven’t responded to medications like clomiphene citrate. However, research shows it doesn’t significantly enhance clinical pregnancy rates, live birth rates, or minimize miscarriage rates. It does lower the rate of multiple pregnancies, but long-term effects on ovarian function remain a concern. For severely overweight women with PCOS, gastric bypass surgery can normalize the reproductive and metabolic abnormalities.
In women older than 45 with AUB, or younger ones with a history of unopposed estrogen exposure, persistent abnormal bleeding or who haven’t responded to medical treatment, endometrial tissue sampling should be performed as a first test due to the risk of hyperplasia and cancer. The ultimate treatment for abnormal bleeding and the prevention of endometrial hyperplasia is hysterectomy, but it’s only for those who don’t intend to have more children. It works immediately and permanently.
Endometrial ablation is another surgical procedure for abnormal uterine bleeding. But it shouldn’t be done in patients with endometrial hyperplasia or cancer. Some patients have developed endometrial cancer after an ablation procedure, so it needs to be prescribed with caution. One study showed that at one year, around 88.3% patients treated with radiofrequency endometrial ablation and 81.7% patients treated with resectoscopic endometrial resection considered their treatment successful. In another study, about 13.4% of women who underwent endometrial ablation subsequently had to have a hysterectomy.
What else can Anovulatory Bleeding (Abnormal Uterine Bleeding) be?
Irregular period accompanied by unusual bleeding, due to issues with ovulation, is a diagnosis that needs careful examination. The medical community uses a classification system called PALM-COEIN to determine the common causes of abnormal uterine bleeding in women who are not pregnant. This system divides the causes into two groups: PALM, which includes physical problems usually treated by surgery, and COEIN, which includes non-physical causes generally treated with medication.
Each letter stands for:
- P: Polyp (abnormal tissue growth)
- A: Adenomyosis (inner lining of the uterus breaks through the muscle wall)
- L: Leiomyoma (non-cancerous growths in the uterus)
- M: Malignancy (cancer)
- C: Coagulopathy (bleeding disorder)
- O: Ovulatory dysfunction (problems with ovulation)
- E: Endometrial (relating to the inner lining of the uterus)
- I: Iatrogenic (caused by medication or treatment)
- N: Not yet classified (others still not yet identified)
When looking at ovulatory dysfunction, specific causes could include:
- Various stages of pregnancy
- The start of menstruation, nearing menopause, or premature ovarian failure
- Breastfeeding
- Hormonal diseases like thyroid problems, high prolactin levels, or pituitary disorder
- Use of certain medications, especially antipsychotics, antidepressants, heart medication verapamil, or anti-nausea drugs
Other, non-uterine reasons for vaginal bleeding can include inflammation of the vagina, injury to the genitals, foreign body, cancer in the outer part of the female genitals and cancer in the vagina.
What to expect with Anovulatory Bleeding (Abnormal Uterine Bleeding)
Generally, patients with AUB-O – abnormal uterine bleeding in ovulatory cycles – have a good overall outlook. Symptoms can typically be managed with medication, leading to a significant boost in the patient’s quality of life. But dealing with AUB-O can occasionally lead to complications, including abnormal growth of cells (hyperplasia) or even cancer.
However, even if it turns out to be endometrial cancer – a cancer that begins in the lining of the uterus – the outlook is relatively better compared to other types of cancers affecting the female reproductive system. Also, for patients who wish to have children, inducing ovulation can be highly successful. According to one study, letrozole and clomiphene citrate – medicines used to stimulate ovulation – achieved live birth rates of 27.5% and 19.1% respectively.
Possible Complications When Diagnosed with Anovulatory Bleeding (Abnormal Uterine Bleeding)
The most common issues resulting from anovulation, a condition where the ovaries don’t release an egg, are infertility and irregular menstrual cycles. Irregular periods can potentially be improved by hormonal birth control. However, if a woman wants to get pregnant, treatment with fertility drugs like clomiphene or letrozole might be appropriate. Depending on their expertise, the patient’s main doctor might need to refer them to a gynecologist for this treatment. Persistent anovulation and too much estrogen can result in endometrial hyperplasia (abnormal growth of the lining of the uterus) and cancer. Therefore, it’s crucial for women with irregular periods due to anovulation (AUB-O) to understand this risk when discussing different treatment options.
Iron-deficiency anemia, a condition characterized by a lack of healthy red blood cells to carry adequate oxygen to body tissues, is the most common complication of having heavy irregular periods. It can be treated with iron given orally or intravenously. Doctors might also suggest that women who are taking oral contraceptives and have symptomatic anemia, skip their placebo week to prevent menstrual bleeding and consequent blood loss.
Sheehan syndrome, a disease that affects the pituitary gland, is a potential risk of having endometrial ablation, a procedure that surgically destroys the lining of the uterus. Patients need to know about this risk before they decide to undergo this treatment.
Preventing Anovulatory Bleeding (Abnormal Uterine Bleeding)
It’s essential for patients to maintain a healthy body weight. Higher weight or obesity can lead to issues with regular ovulation.
Explaining how the female body naturally changes during times like puberty and menopause can help ease any worries related with symptoms of abnormal uterine bleeding during those transitional periods.
Helping patients understand the difference between normal and abnormal bleeding can guide them to know when it’s necessary to arrange a meeting to discuss their bleeding with a medical professional. Delays in spotting and managing any abnormality can result in increased complications related to abnormal uterine bleeding.