The Menstrual Cycle

Among women of childbearing age, there is an expected pattern of the menstrual cycle. The interplay of hormones, receptor sites, growth factors, inhibin, and activin with the granulosa and thecal cells in the ovary is complex. An over-simplified version is:

• Responding to low levels of estrogen, the hypothalamus sends a signal to the anterior pituitary gland to release follicle stimulating hormone (FSH). In addition to stimulating ovarian follicular growth, FSH also stimulates the granulosa cells of the follicle to produce gradually increasing amounts of estrogen. This estrogen has many effects, including stimulation of the endometrium glandular epithelium to proliferate (reproduce), creating an environment that will later prove hospitable for implantation of a fertilized ovum.
• As the estrogen production accelerates, it begins to inhibit FSH and at the same time stimulates luteinizing hormone (LH). This leads to a major surge in LH that peaks 12 to 24 hours before ovulation. This surge in LH is accompanied by a parallel surge in FSH and estrogen.
• After the peak of LH, FSH and estradiol, continuing secretion of LH causes the granulosa cells to produce progesterone. In the absence of pregnancy, the progesterone is produced for about 10 days. Then it and estrogen production rapidly decline, leading to a significant withdrawal of hormonal support from the endometrium. This provokes bleeding as the decidualized endometrium is shed, leaving only the endometrial basal layer of cells.
• Responding to the low levels of estrogen, the hypothalamus again causes release of FSH from the anterior pituitary, and the cycle begins again.

Normal Bleeding

• Occurs approximately once a month (every 26 to 35 days).
• Lasts a limited period of time (3 to 7 days).
• May be heavy for part of the period, but usually does not involve passage of clots.
• Often is preceded by menstrual cramps, bloating and breast tenderness, although not all women experience these premenstrual symptoms.

Abnormal Uterine Bleeding

Abnormal bleeding has a number of definitions, the simplest of which is, “all bleeding that is not normal.” Abnormal bleeding includes:

• Too frequent periods (more often than every 26 days).
• Heavy periods (with passage of large, egg-sized clots).
• Any bleeding at the wrong time, including spotting or pink-tinged vaginal discharge
• Any bleeding lasting longer than 7 days.
• Extremely light periods or no periods at all

Dysfunctional Uterine bleeding

Dysfunctional bleeding is another term with varying definitions. Some consider bleeding dysfunctional if there is any abnormal uterine bleeding in the absence of uterine pathology or medical illness. Others feel that drawing such a fine distinction is pointless as many medical illnesses (polycystic ovary syndrome, hypothyroidism, hyperthyroidism, adrenal hyperplasia) can create a pattern of bleeding that is clinically indistinguishable from the traditional “dysfunctional” uterine bleeding. Many gynecologists use the term abnormal uterine bleeding (AUB) and dysfunctional uterine bleeding (DUB) interchangeably.

Overview

Any woman complaining of abnormal vaginal bleeding should be examined. Occasionally, you will find a laceration of the vagina, a bleeding lesion, or bleeding from the surface of the cervix due to cervicitis. More commonly, you will find bleeding from the uterus coming out through the cervical os.

Excluding pregnancy, there are really only three reasons for abnormal uterine bleeding:

• Mechanical Problems
• Hormonal Problems
• Malignancy

The limited number of possibilities makes your caring for these patients very simple. If the bleeding is heavy, obtain a blood count and assess the rate of blood loss to determine how much margin of safety you have. Someone with a good blood count (hematocrit) and minimal rate of blood loss (less than a heavy period), can tolerate this rate of loss for many days to weeks before the bleeding itself becomes a threat. Determine whether the bleeding is significant enough to begin iron replacement therapy.

Pregnancy Problems

A variety of pregnancy problems can cause vaginal bleeding. These include:

• Abortion (threatened, incomplete, complete, missed, or inevitable)
• Ectopic Pregnancy
• Placental Abruption
• Placenta Previa

If the bleeding patient has a positive pregnancy test, a careful search should be made for each of these problems. However, if the pregnancy test is negative, pregnancy-related bleeding problems are effectively ruled out.

Mechanical Problems

Such problems as uterine fibroids or polyps are examples of mechanical problems inside the uterus.

Since mechanical problems have mechanical solutions, these patients will need surgery of some sort (Polypectomy, D&C, Hysteroscopy, Hysterectomy, Myomectomy, etc.) to resolve their problem.

Polyps visible protruding from the cervix are usually coming from the cervix and can be easily twisted off.

A simple ultrasound scan can reveal the presence of fibroids and their location. Those fibroids that are impinging on the endometrial cavity are the most likely to be responsible for abnormal bleeding.

Endometrial polyps can be identified with a fluid-enhanced ultrasound (sonohysterography), a simple office procedure. They can also be identified during hysteroscopy.

An endometrial biopsy can be useful in ruling out malignancy or premalignant changes among women over age 40. It can also be useful in younger women in identifying the hormonally confused endometrium of anovulatory bleeding, and will sometimes pick up a small piece of endometrial polyp.

Another form of mechanical problem is an IUD causing abnormal bleeding. These should always be removed.

Hormonal Problems

Hormonal causes for abnormal bleeding include anovulation leading to an unstable uterine lining, breakthrough bleeding associated with birth control pills, and spotting at midcycle associated with ovulation. Some of these cases will be related to an underlying medical abnormality, such as polycystic ovary syndrome, hyper or hypothyroidism, adrenal hyperplasia, and pituitary adenoma. Rarely, this may be due to a hormone secreting neoplasm of the ovary.

The solution to all of these problems is to find and treat those underlying medical abnormalities that exist, and/or take control of the patient hormonally and insist (through the use of BCPs) that she have normal, regular periods.

• Thyroid disease can be ruled out clinically or through laboratory testing (TSH)
• Adrenal hyperplasia can be ruled out clinically or through laboratory testing (DHEAS, 17 hydroxyprogesterone, ACTH stimulation test)
• Prolactin-secreting pituitary adenoma can be ruled out clinically or through laboratory testing (serum prolactin)
• Hormone-secreting ovarian neoplasms can be ruled out clinically or through laboratory testing (ultrasound, estradiol, testosterone)
• Anovulation can be confirmed through the use of endometrial biopsy, although for women under age 40, biopsy is only infrequently utilized.

If the abnormal bleeding is light and the patient’s blood count good, starting low-dose BCPs at the next convenient time will usually result in effective control within a month or two.

If the bleeding is quite heavy or her blood low, then it is best to have the patient lie still while you treat her with birth control pills. Some gynecologists have used 4 BCPs per day initially to stop the bleeding, and then taper down after several days to three a day, then two a day and then one a day. If you abruptly drop the dosage, you may provoke a menstrual flow, the very thing you didn’t want.

Alternatively, particularly for those with intractable anovulatory bleeding, plain estrogen in doses of 2.5 up to 25 mg a day can be effective in promoting endometrial proliferation, stopping the bleeding. After the bleeding is initially controlled with estrogen, progesterone is added to stabilize the endometrium, leading up to a hormonal withdrawal flow a week or two later. Two drawbacks to this approach are the nausea that frequently accompanies such large doses of estrogen, and the theoretical risk of thromboembolism among women exposed to large amounts of estrogen while on bed rest.

Giving iron supplements is a good idea (FeSO4 325 mg TID PO or its’ equivalent) for anyone who is bleeding heavily.

Malignancy

Abnormal bleeding can also be a symptom of malignancy, from the vagina, cervix or uterus.

Cancer of the vagina is extraordinarily rare and will present with a palpable, visible, bleeding lesion on the vaginal wall. Cancer of the cervix is more common but a normal Pap smear and normal exam will effectively rule that out. Should you find a bleeding lesion in either the vagina or on the cervix, these should be biopsied.

Factors that increase the risk for endometrial carcinoma include:

• Increased estrogen exposure (exogenous or endogenous)
• Diabetes
• Overweight (through increased conversion of androstenedione to estrone by body fat cells)
• Chronic, untreated anovulation (many years)

Cancer of the uterus (endometrial carcinoma) occurs most often in the older population (post-menopausal) and is virtually unknown in patients under age 35. For those women with abnormal bleeding over age 40, an endometrial biopsy is a wise precaution during the evaluation and treatment of abnormal bleeding.

In evaluating abnormality, you have a number of Diagnostic and Therapeutic Options

 Obtain a Pregnancy test .

 Examine the patient

 Make sure the Pap smear is up to date.

 Biopsy any visible lesions of the cervix or vagina.

 Perform an Endometrial biopsy for women over age 40.

 A Pelvic ultrasound scan can identify fibroids, and a Sonohysterogram can identify intracavitary lesions.

 A Blood count can sometimes be revealing if bleeding has been heavy and prolonged.

 Correct any underlying medical problems

 Begin OCPs to control abnormal bleeding due to hormonal causes. Continuous birth control pills can suppress menstruation completely.

 Depo Provera can be used to suppress ovulation and menstruation .

 D&C (with or without hysteroscopy) can remove endometrial polyps

 If bleeding is intractable and the patient desires to preserve childbearing, consider myomectomy if submucous fibroids are contributing to the bleeding. Sometimes, this can be done hysteroscopically.

 If bleeding is intractable and the patient has completed childbearing, consider balloon or roller-ball ablation of the endometrium, or even hysterectomy.