Family Medicine 17: 55-year-old postmenopausal female

with vaginal bleeding

User: hyunsoo Ellis
Email: helli6925@ung.edu
Date: November 25, 2020 3:44AM

Learning Objectives

The student should be able to:

Define menopause and discuss common symptoms and treatment options.

Develop a differential for postmenopausal bleeding.
Counsel a patient regarding the differential, workup, and follow-up plan for postmenopausal bleeding.
Discuss risk factors for osteoporosis and the recommended screening for osteoporosis.
Counsel patients regarding osteoporosis prevention/treatment.
Discuss the recommended cancer screening for a 50-plus-year-old female.
Describe the risks/benefits of hormone therapy in the postmenopausal female.

Knowledge

Definition of Menopause

Menopause is a normal process that occurs as the ovaries are depleted of follicles and produce less estrogen. It is thought to be
primarily the lack of estrogen that leads to the majority of postmenopausal symptoms.

This happens in the U.S. at a median age of 51.3 years, between 40 and 58 years of age for most patients.

The natural process leading up to menopause may take several years. During the transition, it can be difficult to make a firm
diagnosis. National guidelines define menopause as 12 months without a cycle.

Symptoms of Menopause

Hot flashes or vasomotor symptoms are the most common symptoms of menopause and are present in up to 82% of menopausal
patients. Many patients will also experience symptoms of atrophic vaginitis, which can lead to vaginal dryness and dyspareunia
(pain during intercourse), and urinary symptoms. Since menopause can be associated with a variety of additional problems—
including sexual dysfunction, sleep disturbance, mood disturbance, and concentration difficulties—it can significantly affect a
patient's daily functioning and quality of life.

Initial History for Vaginal Bleeding in Postmenopausal Patients

Detailed description of recent bleeding and any associated symptoms

Last menstrual period
Other gynecological problems or bleeding problems
Family history of cancer or bleeding problems
Detailed medication history, including as-needed medications and/or supplements
Review health maintenance

Screening for Females in Their 50s Without Risk Factors

Mammogram

There are some conflicting recommendations for breast cancer screening at this time:

U.S. Preventive Service Task Force (USPSTF)

Recommends biennial screening mammography for patients with breasts aged 50–74 and that starting screening mammography
prior to 50 years of age should be a decision that is individualized for each patient. (They found insufficient evidence to assess the
benefits and harms for those over age 75.)

The USPSTF recognizes that patients with a first degree relative with a history of breast cancer are at higher risk for breast cancer.
This group may benefit more from screening mammograms in their 40s than those at average risk.

The American Cancer Society (ACS)

Recommends yearly screening mammograms starting at age 45. At age 55 a person can continue to have yearly mammograms or
transition to biennial mammograms.

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 For people between 40 and 44, the ACS recommends having an informed discussion of risks and benefits with the patient.

Mammograms should continue until the patient’s life expectancy is less than 10 years.

The American College of Obstetricians and Gynecologists (ACOG)

Recent ACOG updates in 2017 highlight shared decision-making.

Patients should be offered mammograms starting at age 40 annually or biennially.

Mammograms for screening should be initiated no later than age 50.

Continue mammograms through age 75, then make decisions with consideration for overall health and longevity.

As shared decision making is increasingly highlighted in guidelines, risk assessment tools can be helpful in individualizing
recommendations.

Colon cancer screening

The USPSTF recommends colon cancer screening to begin at age 50 for the average risk patient, irrespective of gender. This
should continue through age 75. The USPSTF recommends against routine screening between ages 76 to 85, but the decision on
whether to screen should be individualized. They recommend against (D grade) screening after the age of 85. The USPSTF has
submitted for comment a new “B” grade recommendation to screen adults age 45-59. This is expected to become official in the
spring of 2021.

In response to increasing rates of colon and rectal cancer at younger ages in people born after 1980, the American Cancer Society
gave a qualified recommendation in 2018 to start colon cancer screening at age 45.

Pap test

Regular screening with Pap tests (cytology) has been very effective at reducing mortality from cervical cancer in screened
populations. Extensive research and newer technologies have allowed for more precise guidelines for cervical cancer screening in
patients of average risk. Recent recommendations from the American Society for Colposcopy and Cervical Pathology and the
USPSTF call for Pap test screening to start at age 21 and continue every three years until age 30. Preferred screening from age 30
to 65 is with HPV testing in addition to the cytology test (Pap) every five years or HPV testing alone every five years.

For people with a cervix with possible gynecologic pathology or certain risk factors—such as HIV, immunosuppression, DES
exposure (while in utero), or history of cervical cancer—more frequent Pap tests may be indicated. These guidelines do not
currently prohibit testing more often if the clinician feels it is indicated, or if the patient requests more frequent screening.
However, insurance coverage for more frequent tests in average risk patients will likely end once these new guidelines are
accepted.

Pap tests are not indicated for patients who have had a hysterectomy, including complete removal of the cervix for noncancer
reasons and do not have a history of CIN2 or greater lesions.

Physical Examination for Abnormal Uterine Bleeding

Pelvic exam: Look for vulvar or vaginal lesions, signs of trauma, and cervical polyps or dysplasia. On bimanual examination,
assess the size and mobility of her uterus, as a firm, fixed uterus would be concerning for uterine cancer.

Neck exam: Thyroid exam to look for goiter or nodules, as thyroid disease is one of several systemic diseases that can cause
dysfunctional uterine bleeding.

Skin exam: Look for evidence of bleeding disorders, like bruises. Also, jaundice on skin exam and hepatomegaly on abdominal
exam might signify an underlying acquired coagulopathy from liver disease.

Symptoms and Findings of Atrophic Vaginitis

Symptoms: Vaginal dryness, dyspareunia, urinary symptoms, and vaginal pruritis.

Urinary symptoms: Recurrent urinary tract infections, urinary frequency, and dysuria. Local estrogen may help patients
with urge incontinence and recurrent urinary tract infections. We're not sure if estrogen helps with overactive bladder, and
there is conflicting evidence about its effect on stress incontinence.
Vaginal pruritis: Local symptoms are usually best treated with topical estrogen in the form of either a vaginal cream or an
estrogen ring, which is an estrogen impregnated ring inserted into the vagina.

Physical exam findings: Smoother vaginal mucosa and cervix, related to postmenopausal changes from decreased estrogen
levels.

Risk Factors for Endometrial Cancer

The following increase the amount of unopposed estrogen and thereby increase the risk for endometrial cancer:

Unopposed estrogen therapy

Tamoxifen (Nolvadex)—Often used in patients with breast cancer or are at high risk for breast cancer and has an estrogenic
effect on the genital tract.
Obesity
Anovulatory cycles
Estrogen-secreting neoplasms
Early menarche (before age 12)
Late menopause (after age 52)
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 Menstrual cycle irregularities
Nulliparity

Conversely, smoking seems to decrease estrogen exposure, thereby decreasing the cancer risk, and oral contraceptive use
increases progestin levels, thus providing protection.

Other risk factors for endometrial cancer include: hypertension, diabetes, hypothyroidism, and breast or colon cancer.

Age is also a risk factor for endometrial cancer: The incidence of endometrial cancer more than doubles from 2.8 cases per
100,000 in those aged 30 to 34 years to 6.1 cases per 100,000 in those aged 35 to 39 years. Thus, the American College of
Obstetricians and Gynecologists recommends endometrial evaluation in patients aged 35 years and older who have abnormal
uterine bleeding.

When to Screen for Osteoporosis

The United States Preventive Services Task Force recommends osteoporosis screening for all females over the age of 65 and for
younger patients who have increased risk of a major osteoporotic fracture (MOF). The FRAX score is a commonly used tool to
assess risk. A ten-year risk of MOF above ~9% may be used to indicate increased risk.

While the USPSTF found insufficient evidence to recommend screening in men, the FRAX includes calculations for men and may
provide useful information about their fracture risk.

Osteoporosis Risk Factors

Corticosteroid use
Family history of osteoporosis, especially if a first-degree relative has fractured a hip
Previous fragility fracture defined as a low-impact fracture
Smoking
Heavy alcohol use
Lower body weight (weight < 70 kg) is the single best predictor of low bone mineral density
In epidemiological studies, African American patients demonstrate higher bone density than White patients at all ages.
White race, therefore, is frequently cited as a risk factor for osteoporosis, and the FRAX tool includes a patient’s race in its
calculations. Students should remember that there is no viable biological definition of race. The observed variations in bone
density may be explained by social determinants of health, and a patient’s family history (i.e., heredity) is a more important
risk factor than their race. Furthermore, there are clear racial disparities in screening, diagnosis, and treatment of
osteoporosis that negatively affect African American patients.

Strategies to Prevent Osteoporosis

Smoking cessation. Smoking increases the risk of osteoporosis.

Adequate intake of calcium and vitamin D are essential to normal human physiology including bone health. A number of
organizations have recommended routine supplementation of these nutrients for a variety of reasons including the prevention of
osteoporosis. However, this recommendation is now being questioned.

The USPSTF concludes that current evidence is insufficient to assess the balance of benefits and harms of daily
supplementation with > 400 IU of vitamin D3 and 1,000 mg of calcium for the primary prevention of fractures in
noninstitutionalized postmenopausal patients. It recommends against daily supplementation with lower doses for the
primary prevention of fractures because there is no demonstrated benefit at this dose and supplementation increases the
risk of nephrolithiasis.
The USPSTF does not address daily dietary requirements of these nutrients; only the use of these supplements to
prevent osteoporosis and certain cancers. It does illuminate the risk of the widespread calcium and vitamin D
supplementation and the relative lack of good research demonstrating benefit for osteoporosis.
Pending further evidence, it is reasonable to encourage otherwise healthy patients at risk for osteoporosis to consume
adequate amounts of calcium and vitamin D. Typical doses would include 1,200 mg of calcium and 800 to 1,000 IU of
vitamin D daily. People of this age typically only consume about 600 to 700 mg of calcium and 156 IU vitamin D daily, in
their diet. Increasing dietary intake of these nutrients should be the first line approach, but supplements may be needed
when adequate dietary intake cannot be achieved and when Vitamin D deficiency is demonstrated. Vitamin D plays a major
role in calcium absorption, bone health, muscle performance, balance, and risk of falling. Chief dietary sources of vitamin D
include fortified milk and cereals, egg yolks, salt-water fish, and liver.
Overuse of calcium and vitamin D can be harmful and patients should be advised against taking high doses of these
supplements, especially without a thoughtful review of their diet and medical history. Unfortunately, patients may get
conflicting information. Approximately 5% of women over 50 exceed the recommended upper intake level of 2,500 mg per
day for calcium. The upper intake level for vitamin D in healthy adults is currently listed as 4,000 IU per day, but that
amount is subject to change as more information becomes available. Students are encouraged to follow emerging research
and recommendations for these nutrients.

Lifelong weight-bearing exercise (bones and muscles work against gravity as the feet and legs bear the body's weight) and
muscle strengthening can improve agility, strength, posture, and balance, which may reduce the risk of falls. It may also modestly
increase bone density. Examples of weight bearing exercise include walking, jogging, Tai Chi, stair climbing, dancing, and tennis.

Osteoporosis: Consequences, Fall Prevention, and Diagnosis

Consequences

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 Patients with osteoporosis can suffer a fracture following even minimal trauma. These fractures are most commonly of the
vertebrae, the hip, distal radius and proximal humerus. The lifetime risk of fracture for a 50-year-old female exceeds her risk of
developing endometrial or breast cancer. Fractures secondary to osteoporosis place an enormous burden on the elderly
personally, medically, and economically. Patients with hip fractures have an average one-year mortality rate of 20–25%. Hip
fractures are associated with significant loss of independence, with 15–25% of previously independent patients requiring nursing
home placement for at least one year, and less than 30% of patients regaining their prefracture level of function.

Fall Prevention

Strategies to reduce falls include: checking and correcting vision and hearing, evaluating any neurological problems, reviewing
prescription medications for side effects affecting balance, and providing a checklist for improving safety at home.

Diagnosis

A DEXA scan is a bone densitometry study that usually looks at the lumbar spine and hip density to determine if someone has
osteoporosis. This is done based on a T-score. A T-score of -1.0 to -2.5 is consistent with decreased bone density or osteopenia.
Osteopenia is not a clinical diagnosis and just indicates the degree of bone decline since peak bone mass. It is usually not an
indication for treatment aside from lifestyle. A T-score of less than -2.5 indicates osteoporosis. Based on the patient's risk for
fracture and their T-score, we can then make recommendations for treatment of osteoporosis.

The T-score is a statistical measure that compares one person's bone mass density (BMD) in standard deviations to the average
peak bone mass density in a young healthy person. A zero value is the average BMD for a young healthy person and the T-score is
then the number of standard deviations from that mean. For instance, a T-score of -1.0 indicates a bone density that is one
standard deviation below the BMD of a young healthy person. This statistic is then used to classify the BMD of an individual into
normal (0 to -1), osteopenia (-1 to -2.5) and osteoporosis (below -2.5).

Clinical Skills

How to Perform a Pelvic Exam

In preparation for the pelvic exam, you elevate the head of the exam table to 30 to 45 degrees. You have the patient slide down on
the exam table and help her position her feet in the stirrups. You carefully cover her legs with a sheet and ask her to relax her
knees outward just beyond the angle of the stirrups.

You let the patient know you are about to begin the speculum exam. When she has acknowledged this, you insert a warm,
lubricated speculum. ​

You obtain a Pap test. You then remove the speculum and perform a bimanual exam.

How to Perform Endometrial Biopsy Procedure

Prior to the procedure, verify that the patient understands the procedure and the risks of (1) bleeding or (2) uterine perforation
(which is rare), and signs a consent form.

First, have the patient get into the lithotomy position and insert a speculum.
Use betadine solution to cleanse the cervix.
Then, use a tenaculum (forceps with a sharp hook at the end of each jaw used for grasping tissues in surgery) to grasp the
cervix on the superior/anterior portion.
Next, insert the pipelle into the os and obtain specimens from at least four different areas of the uterus.
Withdraw the pipelle and place the samples into the formalin. Remove the tenaculum and speculum.
The specimen is sent in formalin to the lab.

In-depth review of endometrial biopsy procedure

Management

Benefits and Risks of Menopausal Hormone Therapy

Benefits of menopausal hormonal therapy

The primary function of menopausal hormonal therapy (HT) is to treat the bothersome symptoms of menopause.

Systemic estrogen is the most effective treatment for hot flashes or vasomotor symptoms. Patients with an intact uterus
must also be treated with progesterone to decrease the risk of endometrial cancer related to unopposed estrogen.
Estrogen, especially when used topically, is also the most effective treatment for symptoms of atrophic vaginitis, including
vaginal dryness and dyspareunia, and may improve urinary symptoms such as urge incontinence and recurrent urinary
tract infections. Topical estrogens (available as an insert, cream, ring) are safe in low doses and in low doses probably do
not require coverage with progesterone even in patients with an intact uterus.
Menopausal hormonal therapy (HT), especially when started in the first five years after menopause, helps prevent
osteoporosis by maintaining bone density. For many years, HT was used extensively for this purpose. While osteoporosis
prevention may be a benefit of HT used to treat menopausal symptoms, it is not recommended as an agent for the purpose
of osteoporosis prevention. The USPSTF gives this a D rating for the average patient risk, as the harms outweigh the
benefits. It is still considered an option when the risk and benefit ratio favor it over other treatments.
Research on the use of HT for other quality of life issues, including cognitive and depressive symptoms, which commonly

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 occur in perimenopausal and postmenopausal patients, is less clear.

Risks of menopausal hormonal therapy

While the particular risks for groups of patients are still being defined, recent reviews of the available evidence have provided
some key practice recommendations including:

1. Combined estrogen and progestogen use beyond three years increases the risk of breast cancer.
2. Use of unopposed systemic estrogen in patients with a uterus increases endometrial cancer risk.
3. Beginning HT after age 60 increases the risk of coronary artery disease.
4. HT increases the risk of stroke at least for the first one to two years of use.
5. HT for menopausal symptoms should use the lowest effective doses for the shortest possible time.

Hormone therapy includes use of estrogen alone or use of estrogen combined with progesterone. It can improve health-related
quality of life by improving vasomotor and atrophic symptoms caused by menopause. Routine use of HT decreased when
research, including the Women's Health Initiative (WHI), revealed greater than expected risks associated with HT for the subjects
in their study. But it remains an acceptable consideration in younger patients before the age of 60 with few risk factors.

Risks and benefits of HRT

Combined estrogen/progesterone Estrogen alone

Harms per 10,000 person years Harms per 10,000 person years

Breast cancer 9 Dementia 12

CAD 8 Gallbladder disease 30

Dementia 22 Stroke 11

Gallbladder disease 21 DVT 11

Stroke 9 Incontinence 1,261

DVT 21

Incontinence 876

Benefits per 10,000 person years Benefits per 10,000 person years

Diabetes -7 Breast cancer -7

Fractures -53 Fractures -53

Colorectal cancer -19 Diabetes -19

Table adapted from: Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women. US Preventive
Services Task Force Recommendation Statement. JAMA. 2017;318(22):2224-2233. doi:10.1001/jama.2017.18261

How to Decide When to Use Hormonal Therapy

Hormone therapy can be helpful for the symptoms of hot flashes and it will help delay bone loss, but it can increase the risk of
breast cancer, heart attack, stroke, DVT, and incontinence.

Whether or not to use HT can be a difficult decision and must be individualized for each patient.

There is not a right answer for all patients, and our answers change as new evidence becomes available. Our role as providers is
to use the best evidence we have to help patients identify their own unique risks for adverse effects from HT. Then we can help
the patient weigh the potential benefits against her personal risks.

Risk factors to consider include:

Age
Family and personal history of heart disease, stroke, breast cancer, blood clots, or osteoporosis
Medications

Quality of life plays a large role in this decision.

How bothersome are the menopausal symptoms?

What are the patient's preferences in taking medication versus herbal preparations?
What are their fears?

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 Shared decision-making:

In these situations where there is no right answer, the role of the clinician is more of a counselor and to provide information. The
responsibility of decision-making shifts to the patient, as only they can balance their quality of life against the risks they are willing
to accept.

In general, HT for menopausal symptoms should use the lowest effective doses for the shortest possible time, which means we
should discuss the risks and benefits of continuing the therapy with patients frequently.

Osteoporosis Treatment

Biphosphonates are potent inhibitors of bone resorption and reduce bone turnover, resulting in increase in bone mineral
density. Bisphosphonates have been shown to decrease the risk of vertebral and nonvertebral fractures.

Alendronate (Fosamax) and risedronate (Actonel) are available in generic form, making them more affordable.
Ibandronate (Boniva) is only available by trade name and the cost may be prohibitive to some patients.
Zoledronic acid, an intravenous preparation, is given annually and can be used in patients who do not tolerate the oral
bisphosphonates.

Teriparatide (Forteo) is a parathyroid hormone analog and is approved by the FDA for those with osteoporosis at high risk
for fracture. It is given subcutaneously and has been shown to decrease fracture risk by 50% to 65%. It does not have
demonstrated efficacy and safety beyond two years and is quite costly.

Raloxifene is a selective estrogen receptor modulator (SERM) which is used if bisphosphonates are not tolerated, but only work to
prevent vertebral fractures.

Calcitonin has been shown to reduce vertebral fractures, but not hip or other fractures. For most patients, more effective
treatments are available.

Denosumab is an alternate second-line therapy for patients at high risk of osteoporotic fracture. It inhibits osteoclast formation
and survival thereby reducing bone resorption. It is administered in an IV infusion every 6 months and is very costly.

Management of Hot Flashes

Hormone therapy still has a role for the treatment of hot flashes and other menopausal symptoms in patients at low risk for
hormone-related diseases but should be used at the minimum effective dose for the least amount of time. Other prescription
medications, including the antidepressants SSRIs and SNRIs , and clonidine and gabapentin, although less effective than HT
for vasomotor symptoms, can be beneficial in selected patients.

The National Center for Complementary and Integrative Health (NCCIH) is the Federal Government's lead agency for scientific
research on the diverse medical and health care systems, practices, and products that are not generally considered part of
conventional medicine.

NCCIH identified some weak evidence to support the use of hypnotherapy and mindfulness for the management of menopausal
symptoms, but outlines specific concerns and recommends against the use of compounded hormones marketed as bioidentical
hormone replacement therapy and against the use of DHEA. Furthermore, natural medicines, such as phytoestrogens and
botanicals, have not been shown to be clearly safe and effective according to usual standards for prescription medications.

Information from The National Center for Complementary and Integrative Health (NCCIH) publication Menopausal Symptoms and
Complementary Health Practices:

Yoga, tai chi, qi gong, and acupuncture :

There is inconsistent evidence to support their effectiveness.

Phytoestrogens are found in certain plants such as soy and red clover:

There is inconsistent evidence to support their use and they may be harmful in certain patients, particularly those with cancer.
Products made from these plants can act like estrogen in the body, but more research needs to be done before they can be widely
recommended for the treatment of menopausal symptoms. They may not be safe for patients at risk for hormonally related
diseases.

Botanicals such as black cohosh, dong quai, and kava:

Black cohosh (Actaea racemosa, Cimicifuga racemosa): A 2012 Cochrane review found no benefit from the use of
black cohosh for treating hot flashes.
Dong quai (Angelica sinensis): A single randomized trial of dong quai for menopausal symptoms failed to show any
benefit compared to placebo.

Bioidentical hormone replacement therapy and DHEA:

Bioidentical hormone replacement therapy is a marketing term for hormone containing medicines prepared in special pharmacies.
Their content isn't regulated in the way that prescription medications are, and they have not been tested or approved by the FDA.
Their safety cannot be assumed and they lack clear prescribing guidelines.

DHEA is sold as a dietary supplement and is metabolized into estrogen and testosterone in the body. It has not been proven to be
safe or effective and may increase the risk of hormone-related diseases.

Studies

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 Evaluation of Postmenopausal Abnormal Bleeding

Transvaginal ultrasound (TVUS)

TVUS may be the most cost-effective initial test in patients at low risk for endometrial cancer who have abnormal uterine
bleeding. It will tell us the thickness of the endometrium. If the endometrium is less than 4 mm (some sources say < 5 mm) on
ultrasound, it is reassuring and more workup may not be necessary unless the bleeding continues. Besides endometrial
thickening, transvaginal ultrasonography may reveal leiomyoma (fibroids) or focal uterine masses, and may also reveal ovarian
pathology. Although this imaging modality may miss endometrial polyps and submucosal fibroids, it is highly sensitive for the
detection of endometrial cancer (96%) and endometrial abnormality (92%).

Endometrial biopsy

Office-based sampling using the Pipelle device has a sensitivity for detecting endometrial cancer in postmenopausal women as
high as 99%. An endometrial biopsy will obtain a tissue sample that will be sent to Pathology to look for evidence of endometrial
hyperplasia or endometrial cancer.

Complete blood count

A complete blood count might be helpful to demonstrate the absence of anemia and thrombocytopenia. An abnormal result would
trigger further systemic evaluation.

Thyroid-stimulating hormone level

Thyroid disorders may cause abnormal uterine bleeding and are associated with an increased risk for endometrial cancer. We
assess thyroid function via the thyroid-stimulating hormone (TSH). This is an inexpensive test.

Clinical Reasoning

Differential of Abnormal Uterine Bleeding

Most Important / Most Likely Diagnoses

Most common in postpartum and perimenopausal patients ; rare in premenstrual and

Cervical postmenopausal patients.
polyps Although cervical polyps are rare in post-menopausal patients, they can occur and if present, can cause
vaginal bleeding.

With or without atypia can cause bleeding.

Endometrial Simple hyperplasia progresses to cancer in less than 5% of patients; atypical complex hyperplasia is a
hyperplasia premalignant lesion that has a 25% probability of progressing to cancer. Therefore, careful
monitoring and treatment is important with this disorder.

Rare

Hormone- Most ovarian cancers do not cause postmenopausal bleeding or other significant symptoms, but
producing postmenopausal bleeding is one of several symptoms associated with a higher risk for ovarian
ovarian cancer (6.6 fold increased risk).
tumors
Other possible symptoms of ovarian cancer include pelvic or abdominal pain, increase in abdominal size or
bloating, and difficulty eating or feeling full.

The fourth most common cancer in patients with uteri , and the main diagnosis that must be
considered in such patients presenting with postmenopausal bleeding.
Endometrial
Also must be considered in patients over the age of 35 with symptoms suggestive of anovulatory bleeding
cancer
(spotting, menorrhagia, metrorrhagia).

Ninety percent of patients with endometrial cancer have abnormal vaginal bleeding.

Normal response to estrogen stimulation in premenopausal patients.

Proliferative Occasionally postmenopausal patients, particularly those in higher estrogen states, can produce a similar
endometrium endometrial response.

On biopsy, this condition may be hard to differentiate from simple hyperplasia.

Other possible causes of abnormal uterine bleeding

Other possible causes of abnormal uterine bleeding across the age spectrum are: medications (including anticoagulants, selective
serotonin reuptake inhibitors, antipsychotics, corticosteroids, and hormonal medications) and disorders involving the thyroid,
hematologic, hepatic, adrenal, pituitary, and hypothalamic systems.

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