Prepubertal girls lack estrogenization of the vagina and may have poor hygiene, both of which can predispose them to vulvovaginal issues [2]. Prepubertal or pediatric cases of vaginal bleeding are most often caused by either a foreign body (usually toilet paper) or a vulvovaginal irritation or infection [3]. In some cases, the presence of a foreign body will result in a bloody, foul-smelling vaginal discharge. There may be a reactive, irritated area of vaginal mucosa even if the foreign body is no longer retained [2].

Vaginal Streptococcus pyogenes (group A, beta-hemolytic streptococci) can result in vaginal bleeding and may or may not be associated with a nasopharyngeal, perianal, or skin infection or psoriasis [50]. Inspection of the vulva and perianal skin can show a beefy, bright red appearance [3]. Shigella infection can also cause a bloody vaginal discharge that is not necessarily associated with diarrhea [2]. Candida albicans infections are rare in prepubertal girls, given their poorly estrogenized tissues; however, it should be considered if the patient in question has recently taken antibiotics or is diabetic, immunosuppressed, or still in diapers [3].

In reproductive-age women, trauma to the vulva (e.g., straddle injury, sexual trauma) can certainly produce vaginal or vulvar bleeding. A thorough pelvic examination is in order.

The only vulvar lesion of an STI that bleeds easily is the ulcer of granuloma inguinale (donovanosis), caused by Klebsiella granulomatis (previously known as Calymmatobacterium granulomatis). Other ulcerating STIs, such as herpes simplex and syphilis, do not often have bleeding as a primary complaint; however, any bleeding lesion must be evaluated and tested [2]. Gonorrheal infections (Neisseria gonorrhoeae) can produce abnormal vaginal bleeding. Bleeding is usually not seen with chlamydial infections (Chlamydia trachomatis), but any patient with unusual bleeding should be evaluated for cervicitis [2].

Malignant lesions are also a concern in women of childbearing age. Cervical intraepithelial neoplasia (CIN) and cervical carcinoma can present with bleeding, particularly postcoital bleeding [4]. The median age for diagnosis of cervical cancer is 50 years, and the incidence rate is nearly twice as high for women older than 50 years of age as younger women [22]. However, the prevalence of CIN is highest among women in their 20s and 30s [30].

The first concern with postmenopausal bleeding is to rule out uterine adenocarcinoma, as will be addressed later in this course. One of the most common causes of vaginal or vulvar bleeding in a postmenopausal woman is simply atrophy of the vulvovaginal tissues, resulting in bleeding with manipulation or sex. Pruritus is another common complaint in postmenopausal women whose vulvar tissues are lacking in estrogen support [2]. All women with vulvar bleeding should be evaluated for vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, carcinoma, and benign skin lesions such as lichen sclerosus and lichen planus. A vulvar biopsy is usually necessary and is considered the criterion standard to obtain a precise diagnosis [2].

Treatment of any pertinent infection or dermatologic condition should resolve vaginal bleeding in prepubertal patients. Group A streptococcus is treated with penicillin, Shigella with trimethoprim/sulfamethoxazole (if species known; not for empiric therapy), Candida with an antifungal cream, pinworm with oral mebendazole, and gonorrhea with azithromycin (to cover for antibiotic resistant strains and chlamydia) if the child's weight is equal to or greater than 45 kg [2,31,46]. Gonococcal infection in children with body weight less than 45 kg should be treated with erythromycin or ethyl succinate.

Improving hygiene and avoiding irritants will resolve most cases of irritative vulvovaginitis. Lichen sclerosus is treated by removing irritants, using a soothing ointment to protect and heal affected skin, avoiding bicycle riding and other straddle sports, and short-term steroid ointment for persistent cases. Cases that resist these treatments will usually improve or resolve at puberty [2].

The most effective treatment for bleeding resulting from vulvovaginal atrophy is local estrogen replacement. Estrogen may be applied topically as a cream or inserted vaginally as a suppository or ring. Soothing ointments, available over the counter, may be used if the woman does not desire local hormonal treatment. Certain dermatoses, such as lichen sclerosus or lichen planus, may require treatment with a high-potency topical steroid ointment [2].

Ultrasonography is the first-line imaging technique for viewing any structural pathology of the uterus and ovaries [7]. Sonohysterography (or saline infusion hysterography) involves the installation of saline into the uterine cavity, followed by ultrasound exam. This helps to elucidate any intracavitary structural elements, such as polyps or fibroids [7]. Magnetic resonance imaging (MRI) may be required to distinguish a rapidly enlarging leiomyoma from a sarcoma [10].

Leiomyomata are further subclassified, describing whether fibroids are submucosal (SM) versus others (O), as submucosal fibroids are thought to be more likely to contribute to AUB. A tertiary classification further describes their location. SM0 describes an intracavitary lesion; SM1 is <50% intramural, and SM2 is >50% intramural. O3 is 100% intramural but does contact the endometrium. O4 is purely intramural, O5 is subserosal >50% intramural, O6 is subserosal <50% intramural, O7 is subserosal pedunculated, and O8 requires specification of the location (cervical, for example). Fibroids that involve both the endometrium and serosa are given a hybrid number (2-5, for example). Because this tertiary description would likely require use of MRI for evaluation, it is usually left off [16]. Thus, a patient with abnormal bleeding and a known submucosal fibroid would be classified AUB P₀ A₀ L_1(SM) M₀-C₀ O₀ E₀ I₀ N₀, or more simply, AUB-L_1{SM}.

Bleeding should be described by four characteristics: regularity (irregular, regular, absent), frequency (frequent, normal, infrequent), duration (prolonged, normal, shortened), and volume (heavy, normal, light). For regularity, periods may vary by 2 to 20 days; variation of more than 20 days is irregular. Normal frequency is 24 to 38 days, normal duration is 4.5 to 8 days, and normal volume is 5 mL to 80 mL [8]. These "normal" characteristics fall between the 5th and 95th percentile of women. Thus, what was previously termed menometrorrhagia may now be described as irregular, frequent, prolonged, heavy uterine bleeding [8]. Any additional abnormalities can be separately described, such as intermenstrual bleeding and premenstrual spotting.

When preservation of the uterus is desired for future fertility, myomectomy is a valid option, although it will often obligate the patient to cesarean delivery of subsequent pregnancies, depending on the extent of surgery [1,11]. Traditionally, myomectomy has been performed via laparotomy; however, laparoscopic and robotic approaches are becoming more common. Myomectomy cannot always remove all fibroids, and the risk of recurrence and further growth of leiomyomata persists. It appears that the risk of recurrence increases with the number of leiomyomata in the uterus [10].

Abdominal myomectomy carries similar surgical morbidity rates to hysterectomy, and the risk of conversion to hysterectomy is around 1% [10]. Laparoscopic myomectomy improves recovery time and results in less blood loss, unless the fibroids are large. It is limited by the size of the leiomyomata, and because it requires advanced laparoscopic suturing techniques, it is usually only offered by advanced laparoscopic surgeons [10].

Intramural injection of vasopressin with any form of myomectomy decreases surgical blood loss [10]. Preoperative use of GnRH agonists for three to four months to shrink fibroids also results in a lower surgical blood loss [1].

Hysterectomy remains the definitive treatment for women who fail medical management and/or who do not desire childbearing [49]. Fibroids are the most common indication for hysterectomy, accounting for more than 30% of hysterectomies in white women and more than 50% of those in black women [11]. Surgical risks of hysterectomy are higher in those operations done for fibroids compared with other indications, but there is no possibility of recurrence of leiomyoma [1]. Patient satisfaction rates are higher for hysterectomy than for other surgical methods [1,10].

Endometrial (uterine) adenocarcinoma is the most common gynecologic cancer in the United States, and 90% of patients will present with vaginal bleeding [16]. The incidence peaks between 55 and 69 years of age. The primary risk factor for developing endometrial adenocarcinoma is unopposed estrogen, either pharmacologic or through obesity, nulliparity, or late menopause [9]. Hereditary nonpolyposis colorectal cancer syndrome (HNPCC) carries a lifetime risk of endometrial cancer of up to 60% [7].

The ACOG recommends endometrial sampling for adult women 19 to 39 years of age with anovulatory bleeding unresponsive to medication or who have prolonged periods of unopposed estrogen stimulation and for younger women with risk factors such as obesity and longstanding, untreated anovulation [5]. All postmenopausal bleeding must be evaluated, but the traditional thinking that every postmenopausal patient must undergo an endometrial biopsy or dilation and curettage for diagnosis is obsolete. A transvaginal ultrasound showing an endometrial thickness of 4 mm or less in a postmenopausal woman has a negative predictive value approaching 100%. Because of this, an ultrasound can be the first diagnostic tool for a lower-risk (non-obese) woman. An ultrasound is also useful when a biopsy sample yields insufficient tissue for diagnosis. If the endometrial thickness is 4 mm or less, carcinoma is reliably excluded [16]. By using the ultrasound first, a woman can be spared a painful office procedure or a trip to the operating room for dilation and curettage [2].

Anovulatory bleeding is defined by the ACOG as noncyclic menstrual blood flow that is noncyclic, unpredictable, and inconsistent in volume, resulting from continual endometrial proliferation without progesterone-withdrawal-induced shedding and bleeding, due to a lack of ovulation [5]. In a normal menstrual cycle, the endometrium will respond to hormonal stimulation by first proliferating under the influence of estrogen (the production of which is stimulated by FSH from the anterior pituitary), then entering the secretory phase with a surge in LH triggering ovulation. The secretory phase, also called the luteal phase, combines estrogen and progesterone stimulation of the endometrium, resulting in maturation of the stroma [18]. With the withdrawal of estrogen and progesterone, the thickened lining will desquamate and shed, resulting in menstrual blood flow, or the normal period [5].

When ovulation does not occur, the hormonal stimulation will be that of estrogen alone, as there is no corpus luteum to produce progesterone. This unopposed estrogen leads to unsustainable growth of the endometrium. There is no maturing effect of progesterone, so the endometrium grows to an abnormal thickness without strong stromal support [18]. The lining is fragile and unstable and undergoes spontaneous superficial breakage and bleeding. As one site heals, another site of breakdown will appear. The bleeding involves random portions of the endometrium at variable times and in asynchronous sequences [18].

There is ongoing research showing there are altered prostaglandin levels and ratios in the anovulatory endometrium that may impair vasoconstriction [5]. The result, regardless of the cause, is irregular, prolonged, and often heavy uterine bleeding. As the bleeding is caused by abnormalities in the hypothalamic-pituitary-ovarian axis, there is no distinct pathology to be seen under the microscope [1].

It is important to keep in mind that anatomic causes of bleeding must be excluded before the diagnosis of anovulatory or abnormal uterine bleeding can be made [5]. In addition, pregnancy must be excluded first in any reproductive-age woman with irregular bleeding [5]. While irregular bleeding is common in adolescents and may be considered physiologic as long as blood dyscrasias are ruled out in patients with excessive bleeding, adult women should be evaluated for the cause of any irregular bleeding.

Polycystic ovarian syndrome (PCOS) is a common cause of secondary amenorrhea or unpredictable bleeding, occurring in 5% to 10% of women of childbearing age [35]. Along with menstrual irregularities, obesity and hirsutism are common findings in women with PCOS.

The polycystic ovary has a typical thickened appearance on inspection, resulting from chronic anovulation. FSH stimulates follicle development in the ovary, but as the FSH level in PCOS is depressed, the follicles do not reach full maturity and do not ovulate. They remain within the ovary, producing steroid hormones. The increased LH levels in PCOS stimulate ovarian theca cells to produce androstenedione and testosterone, which go on to suppress sex hormone-binding globulin (SHBG), leading to increased free estrogen and testosterone. The increased theca cells contribute to the thickened appearance of the ovary. This self-perpetuating cycle can start from any number of points, but the end result is anovulation resulting in the polycystic ovary—the appearance of the ovary is a symptom and not the disease itself [18].

Although polycystic ovaries are often seen in women with PCOS, ultrasonography is not sufficient for diagnosis of the condition, as up to 62% of the healthy (i.e., normo-ovulatory) population 25 to 30 years of age has polycystic-appearing ovaries; incidence decreases with age due to natural egg loss [47]. There are different sets of criteria for the diagnosis, but all include either clinical or biochemical hyperandrogenism and menstrual irregularities [21]. Women with PCOS have increased peripheral conversion of androgens to estrogens, decreased levels of SHBG (leading to increased free estradiol and testosterone), and increased insulin levels [18].

Other causes of anovulation include thyroid disease, hyperprolactinemia, and hypogonadism brought about by anorexia or excessive exercise [5]. Mental stress can play a role, as can weight loss or obesity [7,11].

A careful history should be taken to elicit other symptoms of thyroid disease, galactorrhea (which occurs in one-third of women with hyperprolactinemia), or anorexia. Certain medications—such as antipsychotics—may cause hyperprolactinemia and thus affect menstrual cycles. Anorexia or weight loss will often cause amenorrhea but can also produce irregular bleeding [18]. A low FSH level indicates that the irregular bleeding is the result of psychologic stress, anorexia, or excessive exercise [5].

The ACOG recommends endometrial sampling for adult women older than 45 years of age with anovulatory bleeding and sampling for women older than 19 years of age with anovulatory bleeding who do not respond to medical therapy or who have prolonged periods of unopposed estrogen stimulation [5]. The incidence of endometrial carcinoma in all women was 29.1 per 100,000 in 2021, with most cases occurring in women 55 to 74 years of age (median age at diagnosis: 64 years) [36]. The lifetime risk of endometrial carcinoma is 3.1%.

Younger adult women should be offered endometrial sampling if they have risk factors for endometrial hyperplasia/carcinoma, such as obesity or chronic anovulation with long periods of unopposed estrogen. More than two to three years of untreated anovulatory bleeding warrants an endometrial biopsy [5]. The incidence of endometrial carcinoma in girls younger than 19 years of age was less than 0.1 per 100,000 in 2017–2021, and only 1.8% of new cases occurred in women 20 to 34 years of age, yet obesity may increase risk for hyperplasia and carcinoma due to unopposed estrogen from chronic anovulation as well as conversion of androgens to estrogens in adipose tissue [5,36].

Endometrial ablation may reduce heavy bleeding and help to avoid anemia, but amenorrhea cannot be guaranteed and should not be the patient's expectation. Endometrial ablation aims to destroy all or most of the endometrium (including the basal glands from which the endometrium develops), which in turn will reduce or eliminate menstrual bleeding [39]. The goal is to decrease the amount of bleeding to a manageable level.

Endometrial ablation may be performed with or without a hysteroscope. The trend is toward nonhysteroscopic methods, which avoid the risk of fluid overload. These are termed second-generation ablation methods and include microwave, hydrothermablation, and cryotherapy [39]. Two more common nonhysteroscopic methods used in the United States are the thermal balloon, which heats to 85°C when applied to the inner uterine wall, and bipolar radiofrequency ablation.

Women who recently delivered a pregnancy can have uterine bleeding over and above normal lochia. These women should be evaluated for retained products of conception, gestational trophoblastic disease, and uterine atony or subinvolution of the uterus [5]. It is normal to experience a temporary increase in lochia and bleeding approximately one week after delivery (ranging from 7 to 14 days), lasting for one to two hours, and usually reassurance is all that is needed [6]. If bleeding is extremely heavy or persistent, it should be evaluated.