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9 Abnormal Uterine in the Premenopausal Period

Heleen van Beekhuizen

INTRODUCTION • Metrorrhagia: bleeding at irregular intervals. • Intermenstrual loss (IBL): irregular blood loss Abnormal uterine bleeding (AUB) is a very fre- during a normal . quent symptom in women. The prevalence of AUB is estimated at 12% in the general population Chronic abnormal uterine bleeding and increases with age, reaching 24% in those aged 36–40 years. When it is a single episode of irregular Chronic AUB is defined by the International Fed- blood loss in non-pregnant women, it is most of eration of Gynecology and Obstetrics (FIGO) as the time harmless, but it can also be a first sign of bleeding from the uterine corpus that is abnormal serious pathology such as of the . For in volume, regularity, and/or timing, and has been this reason it is important to do a full gynecological present for the majority of the past 6 months in history, a speculum examination and a vaginal non-pregnant women. exam ination in all women with AUB. For practical purposes it is important to rule out Acute abnormal uterine bleeding (unrecognized) problems or infection in Acute AUB is defined as an episode of heavy bleed- AUB of short duration. A longer duration of AUB ing in non-pregnant women that, in the opinion of points to more structural abnormalities like fibroids, the clinician, is of sufficient quantity to require im- polyps or malignancies. mediate intervention to prevent further blood loss. This chapter will describe the problems and Acute AUB may present in the context of exist ing how to establish the diagnosis. A flow chart for chronic AUB or might occur without such a history. abnormal uterine bleeding will be introduced. In Chapter 20 appropriate treatment of abnormal CAUSES OF UTERINE BLEEDING uterine bleeding will be explained. For bleeding after the , please see Chapter 10. FIGO have developed a classification system for AUB (Table 1)2. Definition • Polyps and pendiculated fibroids: (generally) benign growths of uterine muscle (fibroids) or endo- Terms like menorrhagia, metrorrhagia, meno- metrium (polyps). metrorrhagia should be abolished as their defini- • : the role of adenomyosis in AUB is tions differ from region to region. It is better to not clear yet. Adenomyosis describes the pres- speak of ‘abnormal uterine bleeding’: ence of endometrial tissue in the . • A normal cycle is between 24 and 35 days with a The sonographic appearance of adenomyosis is period of <7 days. The main menstrual blood partly related to the absolute presence of endo- flow during a period is 35 ml with 65% of metrial tissue in the myometrium and partly due women losing <60 ml each period. to the related myometrial hypertrophy2. • Menorrhagia: regular cycle but blood loss >80 ml • Leiomyoma (fibroids): benign growths of the per cycle1. myo metrium (see Chapter 19).

91 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS

Table 1 FIGO classification system of abnormal uterine likely to progress to (in bleeding. PALM refers to structural abnormalities causing about 25–40%) and should be treated surgic- the abnormal bleeding, COEIN are non-structural causes ally. When no atypia is present conservative ® P Polyps C Coagulopathy treatment with Mirena intrauterine device (IUD) or cyclic (medroxy- A Adenomyosis O Ovulatory dysfunctions progesterone acetate (10 mg/day for 12–14 L Leiomyoma E Endometrial days in the luteal phase of the cycle for 3 months), and repeated sampling is justified. M Malignancy or I Iatrogenic N Cervical ectopia or ectropion can cause spot- hyperplasia N Not yet classified ting and (often in young women or pill users). N Infections: Sexually transmitted infections (STIs) like , urogenital schistoso- miasis or genital tuberculosis. • Malignancies: especially cervical and uterine can- • Iatrogenic causes of AUB are: cer (endometrial cancer or sarcoma, see Chapter N Anticonceptives like combined oral contra- 29) or hyperplasia. Granulosa cell tumors (see ceptives, IUDs. Chapter 28) of the ovaries produce and N Tricyclic antidepressants like amitriptyline cause and AUB and may cause AUB. postmenopausal vaginal bleeding. • (Unrecognized) pregnancy (complications) like mis- • Coagulopathy: abnormal bleeding tendencies are carriage, and molar preg- present in around 13% of women with heavy nancy can cause bleeding and are sometimes menstrual bleeding. mistaken for AUB. • Ovarian dysfunction (formerly dysfunctional uterine bleeding or DUB). The term ovarian dysfunction HISTORY TAKING (OD) is used when hormonal imbalance is present. Common groups affected by OD are: • Duration of complaints (primary/secondary, N Young girls and perimenopausal women: how many months/years). Primary AUB starts both groups have anovulatory cycles (cycles from the first period, secondary AUB starts later without an ovulation). In long-term ano- in the reproductive period. vulation unopposed estrogen stimulation • Duration of periods and regularity of the cycle. (with lack of progesterone) stimulates the • Fever, discharge and can be a endo metrium to become hyperplastic. For sign of STI. is often accompa- menstrual cycle see Chapter 16 on subfertility. nied by foul-smelling discharge and ectopic N Patients with obesity or extreme weight loss. pregnancy by pain! In obesity peripheral fat tissue produces estro- • Swelling in the abdomen is a symptom of gen and morbidly obese women have a high fibroids and ovarian masses but also of unrecog- level of estrogen that disturbs the menstrual nized pregnancy. Ask about fetal movements! cycle. Weight loss and emaceration can lead to • Easy bleeding tendency. Some women have in- anovulatory cycles and cause irregular periods herited bleeding disorders. They often have a • Endometrial causes of AUB are: history of prolonged bleeding during surgery, N A primary disorder of mechanisms regulating trauma or childbirth. It is difficult in low- local endometrial ‘hemostasis’ itself: endo- resource settings to establish the exact diagnosis metrial hemostasis is a very complex process but you can treat heavy periods in these women and local hormonal imbalance in the prosta- the same as in women without bleeding dis- glandin mechanism can cause AUB. orders (see Chapter 20)3,4. Make women with N Endometrial hyperplasia is a precursor to inherited bleeding disorders aware that it is endo metrial cancer and is classified as simplex import ant to deliver in a hospital with blood or complex and with or without atypia. The transfusion possibilities! presenting symptom is most often AUB. • Endocrine disorders like polycystic ovary syn- Endo metrial hyperplasia with atypia is most drome (POC) (see Chapter 16 on subfertility),

92 Abnormal Uterine Bleeding in the Premenopausal Period

, hyperthyroidism and hyper- prolactinemia. Signs of hypothyroidism are irregu lar periods with weight gain, lethargy, obstipation, hair loss (especially at the eyebrows) and a dry skin. Signs of hyperthyroidism are sweating, menorrhagia, palpitations, weight loss, irritability and tremor. Signs of hyperprolactin- emia are bilateral galactorrhea (milk from the nipples), , and (when caused by macroadenoma) headache and disturb- ance of visual fields (see Chapter 16). • Use of contraceptives: many women using pro- gesterone contraceptives such as Depo-Provera®, Implanon® and levonogestrel (LNG) IUD (Mirena®) have irregular blood loss5. Also many women with prolonged combined oral contra- ceptive use can face a period of spotting and postcoital bleeding. • Sexual history: STIs? Sexual abuse? Is pregnancy possible? • Dates of the two last periods and duration of Figure 1 A fibroid in the uterine cavity after bleeding. Are blood clots present during the period or flooding? • IBL: in chlamydia often IBL (spotting) occurs. If possible perform a test for pre-stadia of cervi- cal cancer like a human papillomavirus (HPV) test EXAMINATION or a visual inspection with acetic acid (VIA), see Chapter 26. • Signs of . • PVE: fibroids, pelvic masses, cervical motion • Signs of pregnancy: abdominal distention, blue, tenderness (Figure 1). soft cervix, bigger breasts and nipples. If in doubt: do a . Most of the time you can make the diagnosis and • Obesity or emaciation. treat the patient after history taking and physical • Speculum examination: to establish that blood examination and you do not need (to refer for) loss is from the (and not from the cervix extra investigations. Remember it is important to or ) and to look for signs and symptoms rule out curable life-threatening diseases like ecto- of: pic pregnancy, cervical cancer and STIs as soon as N Cervical carcinoma (see Chapter 26 on cervi- possible. If you do not have facilities for extra cal cancer)? An abnormal cervix can also be investi gations and tests and your history taking and seen in genital schistosomiasis. physical examination were reassuring you can start N ? treatment (see Chapter 20) and review the patient N (see Chapter 17 on STI)? after 2 months. If she is well and irregular blood N Cervical ectopia/ectropion? This can be loss has stopped, there is no need for additional caused by Chlamydia but is also physiological testing. If at review the patient still has irregular in young fertile women and under OC. After blood loss, refer her for extra diagnostic investiga- ruling out (pre-) malignancy and chlamydia tions and tests. infection of the cervix you can use cryo- coagulation in physiological ectropion to re- DIAGNOSTIC INVESTIGATIONS AND duce the bleeding. TESTS THAT CAN HELP N Presence of grainy sandy patches – alterations are considered to be characteristic of schisto- • Hemoglobin (Hb): check for anemia. Severe somiasis in the cervix6. anemia is an indicator of higher blood loss.

93 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS

• Erythrocyte sedimentation rate (ESR) is pro- case of ruptured ectopic pregnancy will also longed in case of infection (and cancer). This is show free abdominal fluid. a simple test that can be performed in many • In thickened on normal ultra- small laboratories. sound, saline infusion ultrasound8 can be helpful • Pregnancy test (UPT) on indication (recent start (see how to do this in Chapter 1 on gynecologi- of AUB). The UPT is positive in normal, non- cal examination). It is easy to differentiate be- viable (missed abortion), ectopic and molar preg- tween endometrial polyps and general thickened nancies and after recent abortion. endometrium. It does not tell you whether the • Urine test or vaginal swab for schistosomiasis in found abnormalities are benign or malignant. endemic areas. Urine test is frequently false- • for histology if suspicion of cervical or negative and the sensitivity of the vaginal swab is endometrial carcinoma. A cervical biopsy can be unknown. A biopsy is probably more sensitive obtained using a special cervical biopsy forceps. to detect schistosomiasis. A biopsy will detect cervical schistosomiasis in • Ultrasound: timing of ultrasound is important if approximately 50% of the patients and almost you want to evaluate the endometrial thickness. 100% of cervical cancer patients. For endo- The best time to perform an ultrasound is just metrial sampling (do this in perimenopausal after the period stopped. In ultrasound you can women with thickened endometrium on ultra- detect thickened endometrium (polyps, hyper- sound after their period) you could use the plasia), fibroids, pregnancy and ovarian masses. smallest cannula of a manual vacuum aspiration A useful cut-off point for thickened endo- (MVA) set (see Chapter 13) or perform a dilata- metrium (measured just after the tion and curettage (D&C). The big advantage of stopped) is around 8 mm in premenopausal a MVA is that you can perform this without women7. In ultrasound you can also see signs of anesthesia in most women. The advantage of pelvic inflammatory disease (PID) such as intra- D&C is that if AUB is caused by polyps the abdominal fluid and abscesses. An ultrasound in D&C can be therapeutic.

Speculum and vaginal examination Check for anemia

Duration of complaints Duration of complaints < 2 months > 2 months

Speculum: normal Do UPT to exclude Speculum Speculum: normal VE: enlarged ectopicDo UPT and to exclude ESR to Cervix abnormal: ectopic and ESR to VE: normal uterus: Do US excludeexclude PIDPID biopsy

AUB:AUB: WhenWhen ESR low and Fibroids: Treat according UPT positive: do US UPTUPT negative: NSAIDs, myomectomy or LNG-IUD,LNG-IUD, tranexamic to results hysterectomy acidacid oror COCCOG (Chap 20)22)

ESR >20 treat Review 2 months: as PID when no relief: do US

When ESR low and UPT negative: NSAIDs, LNG-IUD,LNG-IUD, tranexamic acidacid or COC (Chap 20)22)

Figure 2 Flowchart for management of premenopausal abnormal uterine bleeding (AUB). COC, combined oral contraceptive; DUB, dysfunctional uterine bleeding; ESR, erythrocyte sedimentation rate; NSAIDs, non-steroidal anti- inflammatory drugs; UPT, urine for pregnancy test; US, ultrasound; VE, bimanual vaginal examination

94 Abnormal Uterine Bleeding in the Premenopausal Period

• is an advanced diagnostic test: 2. Munro MG, Critchley HO, Broder MS, Fraser IS. with a scope you can inspect the inside of the FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of uterus. In many low-resource settings this is not reproductive age. Int J Gynaecol Obstet 2011;113:3–13 available yet (see Chapter 1). 3. Madkour A, Finkenzeller D. Abnormal uterine bleed- • HPV or VIA tests to screen for precursor lesions ing. In: Hurt KJ, Guile MW, Bienstock JL, Fox HE, of cervical cancer (see Chapter 26). Wallach EE, eds. The Johns Hopkins Manual of Gynecology and Obstetrics , 4th edn. Philadelphia: Wolters Kluwer, TREATMENT OF ABNORMAL UTERINE Lippincott, Wiliams & Wilkins, 2011;476–85 4. Shankar M, Lee CA, Sabin CA, et al. von Willebrand BLEEDING disease in women with menorrhagia: a systematic re- view. BJOG 2004;111:734–40 Treatment of AUB is described in chapters about 5. Gallos ID, Shehmar M, Thangaratinam S, et al. Oral the causes of AUB: fibroids and cervical cancer, progestogens vs -releasing intrauterine and in Chapter 20 about the treatment of func- system for endometrial hyperplasia: a systematic review tional AUB. and metaanalysis. Am J Obstet Gynecol 2010;203:547e1– 10 FLOWCHART: PREMENOPAUSAL 6. World Health Organization. Report of an informal working group on urogenital schistosomiasis and ABNORMAL BLEEDING HIV transmission. WHO/HTM/NTD/PCT/2010.5. Geneva: WHO, 2009 In the flowchart history taking (duration of the 7. Ozdemir S, Celik C, Gezginc K, et al. Evaluation of problem) and examination (speculum examination endometrial thickness with transvaginal ultrasonography and vaginal examination) are used to stratify to and histopathology in premenopausal women with approp riate treatment (Figure 2). But keep in mind: abnormal vaginal bleeding. Arch Gynecol Obstet 2009; some women with a short duration of complaints 282:395–9 8. de Kroon CD, de Bock GH, Dieben SW, Jansen FW. might have fibroids or cervical cancer! Saline contrast hysterosonography in abnormal uterine bleeding: a systematic review and meta-analysis. BJOG REFERENCES 2003;110:938–47 1. M arret H, Fauconnier A, Chabbert-Buffet N, et al. Clinical practice guidelines on menorrhagia: manage- ment of abnormal uterine bleeding before menopause. Eur J Obstet Gynecol Reprod Biol 2010;152:133–7

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