Dysfunctional Uterine Bleeding

What is coagulopathy (C)?

The term coagulopathy is used to encompass the spectrum of systemic disorders of hemostasis. Such disorders are identifiable in up to 24 percent of women with the symptom of HMB, most commonly mild von Willebrand disease.

What is not otherwise classified (N)?

There exist a number of additional entities that may contribute to or cause AUB in a given individual. These have either been poorly defined, inadequately examined, and/or are extremely rare. Collectively, these entities, those known now or to be discovered in the future, have been placed in a category AUB-N for "not otherwise classified." Examples include arteriovenous malformation and AUB in the context of a uterine isthmocele secondary to a lower segment cesarean section.

What are important components of the physical examination for a patient with AUB?

Vital signs should be assessed and a complete pelvic examination should be performed, with a particular focus on: 1) Potential sites of bleeding from the vulva, vagina, cervix, urethra, anus, or perineum. 2) Any abnormal findings along the genital tract (eg, mass, laceration, ulceration, friable area, vaginal or cervical discharge, foreign body). 3) Size and contour of the uterus -Limited uterine mobility should be noted 4) Current uterine bleeding 5) Presence of an adnexal mass or tenderness

How should you treat patients with AUB and dysmenorrhea or pelvic pain?

Women with adenomyosis or uterine leiomyomas may present with AUB and dysmenorrhea and pelvic pain/pressure. The optimal approach in these patients is to address both issues with one type of treatment. Progestin-based treatments have the potential to address both AUB and dysmenorrhea. Use of the levonorgestrel-releasing (20 mcg/day) intrauterine device (LNg52/5 IUD; Mirena or Liletta) has been found to reduce pain and AUB in women with adenomyosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) are another useful option. Women with fibroids may experience symptoms due to pressure on surrounding viscera, including abdominal or pelvic discomfort, urinary frequency, or constipation. Only treatments that remove or reduce the size of the leiomyomas can simultaneously treat both the pressure and bleeding symptoms. These treatments include gonadotropin-releasing hormone agonists, uterine fibroid embolization, myomectomy, and hysterectomy.

What are indications for treatment of AUB?

Heavy menstrual bleeding (HMB) - HMB is ovulatory (cyclic), heavy bleeding. HMB should be treated when it interferes with quality of life or causes anemia. Intermenstrual bleeding Ovulatory dysfunction (AUB-O) - AUB-O is irregular, nonovulatory (noncyclic) bleeding. Other bleeding patterns

When is surgical treatment indicated for HMB?

Heavy menstrual bleeding (HMB) due to structural lesions (leiomyomas, adenomyosis) is typically the main indication for surgery. The etiologies of ovulatory dysfunction (AUB-O) are medical and are generally treated pharmacologically. The exception to this is patients with AUB-O who desire hysterectomy as definitive treatment.

What are high-dose oral progestins?

High-dose oral progestin formulations are generally used to treat AUB in women who have contraindications to or prefer to avoid estrogen or women who are trying to conceive a pregnancy. Examples of oral progestin regimens used to treat AUB include: ●Norethindrone acetate 5 mg tablets one to three tablets daily ●Medroxyprogesterone acetate 5 to 30 mg daily The contraceptive efficacy of these regimens has not been evaluated, and contraception is required if needed. High-dose progestin formulations (eg, norethindrone 5 mg) may cause progestin-related side effects, including dysphoria, bloating, and an increased appetite.

What is a hysterectomy?

Hysterectomy represents definitive treatment for uterine bleeding. This procedure has a high rate of patient satisfaction because it is curative, is frequently performed after medical management has failed, is not associated with drug-related side effects, and does not require repeated procedures or prolonged follow-up. On the other hand, hysterectomy has a risk of perioperative complications and, depending on the operative approach, a prolonged recovery.

What is a hysteroscopy?

Hysteroscopy provides direct visualization of the endometrial cavity. Diagnostic hysteroscopy can be performed in an office setting. In an operative setting, hysteroscopy allows targeted biopsy or excision of lesions identified during the procedure

When are saline infusion sonohysterography or hysteroscopy indicated?

If intracavitary pathology (lesions that protrude into the uterine cavity [ie, endometrial polyps, submucosal myomas, intramural myomas with an intracavitary component]) is suspected based upon the initial ultrasound, the patient may be evaluated with either saline infusion sonohysterography or hysteroscopy.

How should you treat patients with AUB who are anticoagulated?

In anticoagulated women, neither estrogen-progestin combination contraceptives nor progestin-only methods appears to increase risk of recurrent venous thrombosis. However, because the procoagulant effects of combination contraceptives may persist for up to six weeks after stopping them, it is important to discontinue the contraceptive prior to stopping anticoagulation. Accordingly, in women with a history of VTE on warfarin anticoagulation, we prefer progestin-only therapies, specifically LNg52/5 or DMPA, for treatment of AUB as well as for contraception

What are endometrial causes (E)?

In women with predictable and cyclic menses suggestive of normal ovulation who have AUB, particularly the symptom of HMB but can also include intermenstrual bleeding, and absent other definable causes, the patient is classified as having AUB-E. Most often, the cause of such bleeding is a primary disorder of the endometrium.

What is intermenstrual bleeding?

Intermenstrual bleeding is often due to conditions of the cervix, including cervical cancer, cervical polyps, cervicitis, or ectropion.

What is irregular bleeding (ovulatory dysfunction)?

Irregular uterine bleeding is most commonly associated with ovulatory dysfunction (AUB-O). Women may either have anovulation, which refers to the absence of ovulatory cycles, or oligo-ovulation, in which they shift between ovulatory cycles and anovulation. AUB-O should be suspected in women with an irregular bleeding pattern, particularly those at the extremes of reproductive age (postmenarchal and in the menopausal transition). If a patient has a bleeding pattern consistent with AUB-O, subsequent evaluation is directed toward identifying the cause. In addition, women with prolonged amenorrhea due to ovulatory dysfunction are exposed to unopposed estrogen and are at risk of endometrial hyperplasia or cancer, and endometrial sampling may be required.

What are leiomyomas (L)?

Leiomyomas of the uterus (also referred to as myomas or uterine fibroids) are benign neoplasms of smooth muscle. While the diagnosis of leiomyomas can be suggested by pelvic examination, pelvic imaging is necessary for a more accurate diagnosis.

What is the initial therapy for HMB?

Medical therapy is appropriate initial treatment for most women. For most women with HMB, we suggest estrogen-progestin contraceptives or the LNg52/5 as first-line therapy rather than other medications. Both estrogen-progestin contraceptives and the LNg52/5 are effective treatments for HMB. Both provide effective contraception. Both are well tolerated and have a low risk of adverse effects. The choice between the two depends upon several factors. Estrogen-progestin contraceptives are not an option in patients with a contraindication to estrogen (eg, hypertension or an increased risk of thrombosis). For other patients, the choice depends upon patient preference.

What laboratory values should be assessed in patients with AUB?

Most reproductive-age women with AUB should be evaluated initially with the following tests: 1) Human chorionic gonadotropin (hCG) to exclude pregnancy. -Pregnancy test — Pregnancy should be excluded in all reproductive-age women with AUB. 2) Complete blood count, hemoglobin, and/or hematocrit along with a ferritin level to assess for anemia; the exception to this are patients who do not have heavy or frequent bleeding. -Coagulation disorders typically present as heavy bleeding at menarche or in women in their later reproductive years. For von Willebrand disease, decreasing estrogen levels during the menopausal transition impact von Willebrand factor synthesis.

What is a myomectomy?

Myomectomy is an option for women with uterine leiomyomas. If one or two intracavitary myomas are present, a hysteroscopic myomectomy is minimally invasive and may resolve AUB symptoms. Women with fibroids at other sites that result in AUB may be initially treated with medical therapy. However, laparoscopic or open myomectomy is required if medical management fails and if the patient desires to preserve her fertility. Patients considering myomectomy should be counseled that this surgery may commit them to cesarean delivery for subsequent pregnancies.

What is the role of NSAIDs in the treatment of HMB?

NSAIDs are a nonhormonal, noncontraceptive option for treatment of HMB. NSAIDs used to treat HMB include ibuprofen, naproxen, and mefenamic acid. These drugs are not typically used to treat AUB-O. NSAIDs reduce the volume of menstrual blood loss by causing a decline in the rate of prostaglandin (PGE2 and PGF2 alpha) synthesis in the endometrium, leading to vasoconstriction and reduced bleeding. Advantages of NSAIDs include: ●Do not increase risk of thrombosis ●Low risk of adverse effects ●Reduction of dysmenorrhea ●Low cost and often available over the counter ●Unlike most hormonal therapies, they do not need to be taken daily

What are noncontraceptive estrogen-progestin formulations?

Off-label use of ultra-low estrogen dose formulations marketed for the treatment of menopausal symptoms may be useful in selected women with AUB who have relative contraindications to contraceptive doses of estrogen (eg, older patients who are obese, hypertensive, diabetic, or smokers). Postmenopausal hormone therapy preparations have doses lower than the typical OC dose (20 to 35 mcg ethinyl estradiol). These are not proven as effective contraceptives, and contraception is required if needed (eg, barrier contraceptives). Examples of patients in whom these types of formulations may be useful include women in their late 30s or 40s with: ●AUB-O as well as obesity and/or hypertension ●HMB and uterine leiomyomas as well as obesity and/or hypertension

How is dysfunctional uterine bleeding treated?

Oral contraceptives and NSAIDs

What is ovulatory dysfunction (O)?

Ovulatory dysfunction occurs when a woman is not ovulating, has infrequent ovulation, or, especially in the late reproductive years, experiences luteal out-of-phase events. A luteal out-of-phase event occurs when there is early, luteal phase recruitment of a follicle that then matures precociously, resulting in high circulating levels of estradiol and associated increased menstrual volume. Women with AUB-O typically experience some combination of irregularity of bleeding and a variable volume. While there is often no identifiable cause, ovulatory dysfunction can be related to psychological stress; weight loss or gain; excessive exercise; medications that affect dopamine metabolism; or an endocrine abnormality that impacts the hypothalamic-pituitary-ovarian axis, such as hyperprolactinemia, thyroid disease, and polycystic ovary syndrome.

How does secondary dysmenorrhea present clinically?

Pain with menstruation begins mid-cycle and increases in severity until end. Common women age (20-40's).

How does dysfunctional uterine bleeding present clinically?

Polymenorrhea, menorrhagia and/or metrorrhagia. Unremarkable physical exam.

What are uterine polyps (P)?

Polyps are localized epithelial tumors that include those in the endometrial cavity and the cervical canal. For the present, FIGO categorizes polyps as either being present or absent as defined by hysterosonography (such as saline infusion sonography) and/or hysteroscopic imaging with or without histopathology.

How is dysmenorrhea diagnosed?

Pregnancy testing and pelvic ultrasonography.

What is dysmenorrhea?

Refers to uterine pain around the time of menses, which can either be primary or secondary. Reserved for women whose pain prevents normal activity and requires medication, whether an over-the-counter or a prescription drug. Pain occurs with menses or precedes menses by 1 to 3 days. Pain tends to peak 24 h after the onset of menses and subside after 2 to 3 days.

What is saline infusion sonohysterography?

Saline infusion sonography (also called sonohysterography) is a technique in which sterile saline is instilled into the endometrial cavity and a transvaginal ultrasound examination is performed. This procedure allows for an architectural evaluation of the uterine cavity to detect lesions (eg, polyps or small submucous fibroids) that may be missed or poorly defined by transvaginal sonography alone. SIS is also useful in evaluating AUB associated with cesarean scar defects. Compared with hysteroscopy, the major advantage of SIS is that it can assess the depth of extension of leiomyomas into the myometrium or serosal surface

Who is most likely to be affected by primary dysmenorrhea?

Teens-early 20s, declines with age, no associated pelvic pathology. Risk factors include menarche before age 12, nulliparity, smoking, family history, obesity.

What are iatrogenic causes (I)?

The AUB-I category includes AUB due to medical devices, mainly intrauterine contraception systems, or pharmaceutical therapy. Medications that may cause AUB-I include: -Gonadal steroids (eg, estrogens, progestins, androgens). -Gonadal steroid-related therapy (eg, gonadotropin-releasing hormone analogues, aromatase inhibitors, selective estrogen receptor modulators, selective progesterone receptor modulators). -Anticoagulants. -Systemic agents that contribute to disorders of ovulation, for example, those that interfere with dopamine metabolism or cause hyperprolactinemia. -Intrauterine devices - Bleeding disturbances associated with these devices are recorded as AUB-I. Such systems may be inert, are frequently composites of copper and plastic, or take the form of a local progestogen-releasing system.

What is the Levonorgestrel intrauterine device?

The LNg52/5 is a highly effective and easy to use treatment option for AUB. It may be used as a first-line option for treatment of HMB in women who do not desire pregnancy. In women with AUB-O, use of this IUD does not result in regular bleeding; however, it decreases the risk of hemorrhage and provides protection against endometrial hyperplasia and cancer. Most women using the LNg52/5 develop scant bleeding or amenorrhea. Several considerations apply to use of the LNg52/5 in treating HMB, including the expulsion rate in women with uterine fibroids and the frequency of replacing the device.

What determines the surgical options for patients with HMB?

The choice of whether to proceed with surgery and the type of procedure depends upon plans for fertility. For women who desire future childbearing, surgical options are limited. Myomectomy for women with fibroids is the only fertility-preserving surgical option. For women with intracavitary fibroids, a myomectomy may reduce bleeding and also improve fertility. For women who do not desire to preserve fertility, a minimally invasive option may be appropriate. Procedures include endometrial ablation or uterine artery embolization. Hysterectomy is appropriate for women who have failed other surgical treatments and/or who desire definitive treatment.

When are imaging and hysteroscopy indicated in patients with AUB?

The choice to do imaging is guided by several factors: 1) If the abdominal and/or bimanual pelvic examination findings include an enlarged or globular uterus or adnexal mass, imaging is appropriate to evaluate for leiomyomas, adenomyosis, and adnexal pathology. Imaging may also be useful when ovulatory dysfunction is suspected, as ovarian morphology and dimensions may help establish the diagnosis of polycystic ovarian syndrome. 2) If the pelvic examination is normal, imaging is also appropriate if symptoms persist despite treatment.

What are the most common etiologies of HMB?

The most common etiologies of HMB are: 1) Uterine leiomyomas - HMB associated with uterine leiomyomas is most likely to occur with submucosal leiomyomas, but leiomyomas at other sites may also cause AUB. 2) Adenomyosis - This condition is often accompanied by dysmenorrhea or chronic pelvic pain. 3) Cesarean scar defect - Some two-thirds of women who have had one or (in particular) multiple cesarean births may have a cesarean scar defect, and approximately one-third of women with this condition experience cyclical, postmenstrual bleeding. 4) Bleeding disorder. Others: -Endometrial hyperplasia or carcinoma -IUD -Endometrial polyps, endometritis or PID -Congenital or acquired enhanced myometrial vascularity

How is primary dysmenorrhea treated?

NSAIDs and oral contraceptive pills.

What is primary dysmenorrhea?

No organic cause. Painful uterine muscle activity due to an excess of prostaglandins (F2a).

How does primary dysmenorrhea present clinically?

Pain with menstruation, lower abdominal, intermittent, "labor-like" on days 1-3. Nausea, vomiting, diarrhea (smooth muscle contraction), headache. Normal pelvic exam

What is secondary dysmenorrhea?

Painful menstruation caused by clinically identifiable cause. Etiology: Endometriosis, adenomyosis, polyps, fibroids, PID, IUD, tumors, adhesions, cervical stenosis/lesions, psych.

How does a typical dysmenorrhea patient present?

Patient will present as → a 19-year-old nulligravid college female who complains of dull, throbbing, cramping lower abdominal pain during menses for the past three years. She reports nausea and vomiting during menses but denies irregular or heavy periods, pain with intercourse, or abdominal pain outside of menses. Pain tends to peak 24 h after the onset of menses and subsides after 2 to 3 days. A pelvic exam is normal.

What is the first-line imaging study in women with AUB?

Pelvic ultrasound is the first-line imaging study in women with AUB. Transvaginal examination should be performed, unless there is a reason to not perform the vaginal study (eg, patient declines). Ultrasound is effective at characterizing anatomic as well as vascular uterine pathology and adnexal lesions.

Bonus: What is the average age of menarche?

The average age of menarche is 12 years.

Bonus: What is the average age of menopause?

The average age of menopause is 51 years. Menopause is defined as 12 months of amenorrhea in the absence of other biological or physiological causes. This is typically preceded by several years of irregular uterine bleeding and menopausal symptoms (eg, hot flushes).

What is PALM-COEIN?

The classification system is stratified into nine basic categories that are arranged according to the acronym PALM-COEIN: -Polyp -Adenomyosis -Leiomyoma -Malignancy and hyperplasia -Coagulopathy -Ovulatory dysfunction -Endometrial dysfunction -Iatrogenic -"Not otherwise classified"

When approaching a patient with AUB, what are the most common diagnoses to keep in mind?

The most common etiologies in nonpregnant women are structural uterine pathology (eg, fibroids, endometrial polyps, adenomyosis), ovulatory dysfunction, disorders of hemostasis, or neoplasia.

How should you treat patients with AUB who are trying to conceive a pregnancy?

When counseling a woman regarding treatment of AUB, it is important to ask whether she is planning on trying to conceive a pregnancy in the near future. Treatment of AUB is challenging in this setting. Experts advise that the best option is oral progestin therapy. For women with HMB, NSAIDs may be used but should be stopped upon conception, since they are associated with miscarriage and congenital anomalies.

What is abnormal uterine bleeding (AUB)?

AUB is the overarching term used to describe any symptomatic variation from normal menstruation (in terms of frequency, regularity, duration, or volume) and also includes intermenstrual bleeding. This term covers the full range of symptoms of abnormal bleeding.

What is heavy menstrual bleeding (HMB)?

Based upon current terminology, regular bleeding that is heavy or prolonged (referred to as heavy menstrual bleeding) refers only to cyclic (ovulatory) menses. This replaces the term menorrhagia, which was previously used to describe heavy or prolonged uterine bleeding.

What is the prevalence of AUB?

Chronic abnormal uterine bleeding (AUB), a term that refers to menstrual bleeding of abnormal quantity, duration, or schedule, is a common gynecologic problem, occurring in approximately 10 to 35 percent of women.

How is dysfunctional uterine bleeding diagnosed?

Diagnosis of exclusion, Uterine Dilation and Curettage is the gold standard diagnosis. Urinary β-hCG levels—r/o pregnancy. Labs: CBC, iron studies, PT, PTT, TSH, progesterone, prolactin, FSH, LFTs. Progestin trial—if the bleeding stops, anovulatory cycles confirmed. Ovulation journal, Pap smear. Pelvic U/S, endometrial biopsy, HSG, hysteroscopy.

What is the initial therapy for ovulatory dysfunction?

For women with AUB-O, estrogen-progestin contraceptives, oral progestin therapy, or the LNg52/5 are first-line treatment options, as these approaches reduce bleeding and decrease the risk of endometrial hyperplasia or cancer.

What are characteristics of "normal" menstrual bleeding?

Frequency - 24 to 38 days Duration - ≤8 days. Volume - Research definition is ≤80 mL vaginal "blood" loss per cycle.

What are important historical components to ask a patient who presents with AUB?

1) Is the uterus the source of the bleeding? -Women with AUB typically present with a complaint of vaginal bleeding.. 2) Is the patient premenarchal or postmenopausal? -All postmenopausal bleeding is abnormal, and requires evaluation for endometrial cancer. 3) Is the patient pregnant?

What are indications for endometrial sampling in women with AUB?

Age 45 years to menopause - In women who are ovulatory, any AUB, including intermenstrual bleeding. In any woman, bleeding that is frequent (interval between the onset of bleeding episodes is <21 days), heavy, or prolonged (>5 days). Younger than 45 years - In reproductive-age women, the majority of cases of endometrial neoplasia occur in the setting of ovulatory dysfunction due to estrogenic proliferation with absent or inadequate progestational protection. Endometrial sampling is indicated if AUB is persistent, occurs in the setting of a history of unopposed estrogen exposure (obesity, chronic ovulatory dysfunction) or failed medical management of the bleeding, or in women at high risk of endometrial cancer (eg, tamoxifen therapy, Lynch or Cowden syndrome).

What is Depot medroxyprogesterone acetate?

Depot medroxyprogesterone acetate (DMPA) is typically used for women with AUB who have contraindications to or prefer to avoid estrogen and/or if they prefer this method of contraception. DMPA is not an option for women who are trying to conceive or interested in conceiving in the next one to two years. The contraceptive effect persists for longer than the three-month dosing interval.

What is endometrial ablation?

Endometrial ablation is a minimally invasive option for treatment of heavy or prolonged uterine bleeding when medical therapy fails or in women who do not want to use chronic medical therapy. Pregnancy is contraindicated after endometrial ablation, but contraception is still required. -For women who do not wish to preserve fertility

What are malignancy and hyperplasia (M)?

Endometrial hyperplasia with cytological atypia and carcinoma, including endometrial stromal sarcomas, are epithelial neoplasms of the endometrium that are usually diagnosed with transcervical endometrial sampling.

What are common etiologies of intermenstrual bleeding?

Endometrial polyps Unscheduled bleeding due to a contraceptive method Endometrial hyperplasia or carcinoma or, rarely, uterine sarcoma Endometritis or PID Endometrial abnormalities related to previous endometrial trauma

What are estrogen-progestin contraceptives?

Estrogen-progestin oral contraceptives (OCs) are first-line management for many women with AUB. The advantages of estrogen-progestin contraceptives are that they typically make bleeding more regular, lighter, and reduce dysmenorrhea, as well as provide contraception, if needed. OCs may be prescribed in a cyclic (with a monthly withdrawal bleed), extended (for instance, with a withdrawal bleeding every three months), or continuous (no withdrawal bleed) regimen. OCs are contraindicated in women who are at elevated risk for thrombosis.

What is dysfunctional uterine bleeding?

Excessive uterine bleeding and prolonged menses that is NOT caused by pregnancy or miscarriage, diagnosis of exclusion, look for an underlying endocrine disorder.

What typical bleeding patterns are often seen in AUB?

Heavy menstrual bleeding (HMB) Intermenstrual bleeding Irregular bleeding (ovulatory dysfunction)

What is uterine artery embolization?

Uterine artery embolization is an option for women with uterine leiomyomas. The safety of pregnancy after this procedure has not been established; therefore, it is usually reserved for women who are not contemplating future childbearing.

What is adenomyosis (A)?

Adenomyosis is the presence of endometrial-type glands and stroma within the myometrium, a diagnosis that traditionally requires a histopathologic diagnosis. However, it is now apparent that transvaginal ultrasound or magnetic resonance imaging (MRI) may be used to make a clinical diagnosis of adenomyosis. The role that adenomyosis plays in the genesis of AUB is poorly understood, as some studies have concluded that there is little if any role.

What is the PALM-COEIN classification of AUB?

A comprehensive but flexible classification system for underlying etiologies of AUB has been developed by the International Federation of Gynecology and Obstetrics Menstrual Disorders Committee (FIGO MDC). In general, the components of the PALM group are discrete ("structural") entities that are measurable visually using imaging techniques and/or with histopathology. Meanwhile, the COEI group is related to entities that are not defined by imaging or histopathology ("nonstructural").

What is the etiology of dysfunctional uterine bleeding?

AUB in the absence of an anatomic lesion, caused by a problem with the hypothalamic-pituitary-ovarian axis.

Bonus: What are the characteristics of "normal" menstrual bleeding?

Frequency every 24 to 38 days. Occurs at fairly regular intervals, with a variation from the interval from first day of bleeding of one cycle to the first day of the next of less than 7 to 9 days across cycles. Volume of blood ≥5 to ≤80 mL; clinically, excessive blood loss is defined as a volume that interferes with the woman's physical, emotional, social, and/or material quality of life. Duration is 4.5 to 8 days.

What is the proper history to obtain during an AUB workup?

Gynecologic and obstetric history including: -Menstrual history -Sexual history -History of obstetric or gynecologic surgery -Contraceptive history -Risk factors for endometrial cancer Chronic medical disorders including: -Bleeding disorders -Endocrine disease -Celiac disease Medications

How is secondary dysmenorrhea treated?

Treat underlying cause.

What conditions are treated by treating the primary etiology?

Treatment of certain underlying conditions before initiating other therapy may correct the bleeding or make further treatment more effective. These include structural lesions or etiologies that can be treated pharmacologically. This includes structural lesions. Submucosal fibroids and endometrial polyps can be resected via operative hysteroscopy. AUB due to infection in women with suspected or documented chronic endometritis often resolved following a course of antibiotics.

Which patients should NOT be treated with estrogen therapy?

Treatment with estrogens (ie, estrogen-progestin contraceptives) is contraindicated in women with an increased risk of venous or arterial thrombosis. In general, use of estrogen-progestin contraceptives should be avoided in women with the following characteristics: ●Age ≥35 years and smoking ≥15 cigarettes per day ●Multiple risk factors for arterial cardiovascular disease (such as older age, smoking, diabetes, and hypertension) ●Hypertension ●Venous thromboembolism ●Known thrombogenic mutations ●Known ischemic heart disease ●History of stroke ●Complicated valvular heart disease (pulmonary hypertension, risk for atrial fibrillation, history of subacute bacterial endocarditis) ●Systemic lupus erythematosus (positive or unknown antiphospholipid antibodies) ●Migraine with aura at any age