issues have significant personal, medical, and economic impacts.
From a personal standpoint, menorrhagia is the men- strual symptom most often noted to interfere with daily life. As many as 30% of menstruating women feel that their menses are heavy, while 5% characterize them as very heavy. Perhaps most importantly, 22% describe their menses as a marked or severe problem. 2
From a medical standpoint, abnormal uterine bleeding can be a sign of underlying disease. Information regarding endometrial pathology is only available for women in whom bleeding was alarming enough to indicate dilata- tion and curretage. Within this group, 20% have endo- metrial hyperplasia, a potentially precancerous state. 3
From an economic standpoint, enormous costs have been associated with uterine bleeding. Women with self- described heavy bleeding are 28% less likely to work. 4 However, confounding social and psychological factors may affect both perception of heavy bleeding and employment.
One of the greatest challenges in epidemiologic stud- ies of abnormal uterine bleeding is quantification of men- strual flow. Unfortunately, subjective patient evaluation of volume is largely inaccurate. Less than half of patients with a convincing complaint of menorrhagia actually fit the technical definition of greater than 80 ml of blood loss.
Numerous techniques have been used to quantify menstrual blood loss. Unfortunately, there is no correla- tion between the number of pads or tampons used and the amount of blood loss. Objective approaches, such as alkaline hematin extraction, are the gold standard. 5 Of the subjective approaches, pictorial blood loss assessment charts are the most promising, with 88% sensitivity, although the false-positive rate is 59%. 6
It has also been argued that the common, objective definition of menorrhagia may actually have little rel- evance. Women whose menstrual blood loss is measurably greater than 80 ml have a similar rate of menstrual com- plaints and of anemia as women with less than 80 ml. 7 Thus, the 80 ml cutoff, which was derived from a statistical definition of normal, is a poor predictor of clinical end- points. Evidence suggests that a cutoff of 120 ml would be significantly more predictive of anemia; however, such a high cutoff has not been widely used in studies. 8
Despite these caveats in defining abnormal uterine bleed- ing, much valuable information has been compiled on vari- ous epidemiologic factors that are related to this condition.
PREDISPOSING CHARACTERICS Adolescence
Abnormal uterine bleeding is experienced by almost three-quarters of women in their early teenage years. 9 It is the most common cause of hospital admission for young women. In 46–95% of these cases, anovulation is identi- fied as the main etiology. 10 In up to one-third of cases the menorrhagia has been attributed to coagulopathy. 11
Anovulation in teenage girls is typically related to inadequacy of the ovulation trigger due to an immature hypothalamic–pituitary–ovarian axis. 10 The resulting greater length of estrogen stimulation unopposed by ovu- latory progesterone predisposes to menorrhagia. This pri- marily endocrinologic problem responds to medical management in over 90% of cases. 12 Despite the high rate of abnormal uterine bleeding in adolescent girls, rarely does surgical intervention become necessary. 13
Anovulation is more likely if menarche occurs late.
When menarche is prior to age twelve then half of cycles are ovulatory, while menarche after age twelve portends less frequent ovulation in the first year following menar- che. Within three years postmenarche three-quarters of cycles are ovulatory. The woman’s normal cycle length is established by the sixth year postmenarche. 14
Epidemiology of abnormal uterine bleeding
Michael Zinger
4
Previously undiagnosed coagulopathy is another lead- ing finding in adolescents with menorrhagia. Whereas most other causes of menorrhagia are acquired later in life, coagulopathy causes menorrhagia starting at menarche.
At least 65% of women with menorrhagia related to coagulopathy will report menorrhagia dating back to menar- che, while only 9% of women with menorrhagia not caused by coagulopathy will give this history ( p = 0.001). 15
With increasing physician awareness, coagulopathy is unlikely to remain undiagnosed in women beyond their adolescent years. Thus, the prevalence of undiagnosed coagulopathy is greatest (45%) in girls who present with heavy bleeding with their first period. In girls presenting in the years just after menarche, coagulopathy explains 20% of cases. Additionally, the prevalence of coagulopathy in this group is inversely related to hemoglobin levels. 16
The most common coagulopathies are von Wille- brand's disease and factor XI deficiency, occurring in 13%
and 4%, respectively, of women presenting with unexplained menorrhagia. 17 , 18 Factor X deficiency and heterozygosity for hemophilia were each found in less then 1%. 15
Among 15–19-year-old girls in the USA, the preg- nancy rate is 4.1%. 19 Pregnancy must be kept in mind as a possible cause of abnormal bleeding in this age group.
Perimenopause
The perimenopausal transition is associated with a greater occurrence of abnormal uterine bleeding. The incidence of menorrhagia is significantly increased over the age of 40 years. 20
A typical finding is menorrhagia in conjunction with oligomenorrhea. This is most commonly due to anovula- tion paired with increased estradiol levels. 21 The abnormal bleeding in this group is associated with an increase in endometrial hyperplasia and its associated risks of endo- metrial cancer. 22
Menopause
Uterine bleeding of any amount in menopausal women not receiving hormone replacement should be considered abnormal. When this occurs, endometrial cancer must be suspected. In a study of 245 women undergoing dilata- tion and curretage for postmenopausal bleeding, one- quarter had either endometrial carcinoma or hyperplasia with atypia. Obesity, nulliparity, and age over 60 years old each increased the risk. 23
Fibroids
The presence of fibroids has long been associated with menorrhagia. 24 The cause of this relationship has been
conjectured to involve an overall enlargement of the uter- ine cavity, changes in venous blood flow, and disruption of normal prostaglandin function. 25
Surprisingly, fibroid size is not predictive of menor- rhagia. However, a submucosal location of fibroid does have a strong association with the presence of men- orrhagia. 26
Obesity
Body weight has been linked with anovulation, a caus- ative factor in abnormal bleeding. A body mass index (BMI) of >27 kg/m 2 more than triples the risk. 27 This link is, at least in part, due to the tendencies toward both obesity and anovulation that are seen with polycystic ovarian syndrome.
Although abnormal bleeding in any woman may cause concern regarding the possibility of endometrial cancer, this is a heightened concern when the woman is also over- weight. Obesity is known to significantly increase the risk of endometrial cancer. 28
In contrast, low body weight predisposes to cessation of menstrual flow. Athletes have secondary amenorrhea rates as high as 21%. The likelihood is directly related to decreasing body weight. 29
Tubal sterilization
There is a large body of evidence that the incidence of hysterectomy is greater following surgical tubal ligation.
This has been attributed to changes in utero-ovarian cir- culation that lead to an increase in menstrual abnormali- ties, which in turn lead to hysterectomy. However, numerous confounding factors may be present. Tubal sterilization implies completion of family, a situation that would greatly increase the likelihood for selecting hysterectomy.
Additionally, since these women have chosen a surgical approach to contraception, they may have a more favor- able attitude toward surgery in general. Furthermore, most controls are presumably utilizing another form of contraception, which, in the case of oral contraceptives or injectable progestin, have an ameliorating affect on menorrhagia.
The greatest association between tubal ligation and menstrual disorders was in women who underwent tubal ligation prior to 30 years old. 30 In contrast, a more recent study of almost 10 000 women was able to correct for the confounding effect of oral contraceptives by utilizing controls whose male partners have been sterilized. Inter- estingly, it was found that tubal sterilization decreased the amount and length of menstrual blood loss as well as its associated pain. However, the risk of cycle irregularity did increase with tubal ligation. 31
Coagulopathy
The prevalence of coagulopathy as a cause of abnormal bleeding is discussed in relation to adolescence earlier in this chapter. The converse – i.e. the prevalence of abnormal uterine bleeding in women with known coagulopathy – is addressed here.
Menorrhagia is over twice as likely to occur in women who carry an inherited coagulopathy. The highest prevalence of menorrhagia (78%) is among women with von Wille- brand’s disease. Menorrhagia is less common in women with factor XI deficiency and carriers of hemophilia; under 60%
can be objectively demonstrated to have menorrhagia. 32 EPIDEMIOLOGIC FACTORS IN
TREATMENT CHOICES
Interestingly, multiple unrelated factors play a role in determining treatment of abnormal uterine bleeding.
Women with severe symptoms, those who had not received higher education, those who had completed their family, those who have menstrual pain, and those who are unemployed are more likely to prefer surgical treatment. 33 , 34 Interestingly, psychiatric issues do not play a role. 34 Women with menstrual disorders seeing male physicians are more likely to have surgery. Addi- tionally, they were found to be less likely to participate in treatment decisions but more likely to be satisfied with their care. 35
In a study of British women seeking help for men- strual disorders, there was found to be a strong bias towards stating the diagnosis as a bleeding problem rather than a pain problem. Unfortunately, this appears to affect treatment, as surgical treatment is correlated to the physician’s diagnosis of bleeding and not to the woman’s characterization of her complaint as bleeding. 36
References
1. Shapley M , Jordan K , Croft PR . An epidemiological survey of symptoms of menstrual loss in the community. Br J Gen Pract 2004 ; 54(502) : 359 – 63 .
2. Santer M , Warner P , Wyke S . A Scottish postal survey suggested that the prevailing clinical preoccupation with heavy periods does not reflect the epidemiology of reported symptoms and problems. J Clin Epidemiol 2005 ; 58(11) : 1206 – 10 .
3. Anastasiadis PG , Skaphida PG , Koutlaki NG , et al. Descriptive epidemiology of endometrial hyperplasia in patients with abnor- mal uterine bleeding. Eur J Gynaecol Oncol 2000 ; 21(2) : 131 – 4 .
4. Cote I , Jacobs P , Cumming D . Work loss associated with increased menstrual loss in the United States. Obstet Gynecol 2002 ; 100(4) : 683 – 7 .
5. Fraser IS , McCarron G , Markham R . A preliminary study of factors influencing perception of menstrual blood loss volume.
Am J Obstet Gynecol 1984 ; 149(7) : 788 – 93 .
6. Deeny M , Davis JA . Assessment of menstrual blood loss in women referred for endometrial ablation. Eur J Obstet Gynecol Reprod Biol 1994 ; 57(3) : 179 – 80 .
7. Warner PE , Critchley HO , Lumsden MA, et al. Menorrhagia II:
is the 80-mL blood loss criterion useful in management of com- plaint of menorrhagia? Am J Obstet Gynecol 2004 ; 190(5) : 1224 – 9 .
8. Janssen CA , Scholten PC , Heintz AP . Reconsidering menor- rhagia in gynecological practice. Is a 30-year-old definition still valid? Eur J Obstet Gynecol Reprod Biol 1998 ; 78(1) : 69 – 72 . 9. Friberg B , Orno AK , Lindgren A , Lethagen S . Bleeding disor-
ders among young women: a population-based prevalence study.
Acta Obstet Gynecol Scand 2006 ; 85(2) : 200 – 6 .
10. Deligeoroglou E . Dysfunctional uterine bleeding. Ann NY Acad Sci 1997 ; 816 : 158 – 64 .
11. Smith YR , Quint EH , Hertzberg RB . Menorrhagia in adoles- cents requiring hospitalization. J Pediatr Adolesc Gynecol 1998 ; 11(1) : 13 – 15 .
12. Falcone T , Desjardins C , Bourque J et al. Dysfunctional uterine bleeding in adolescents. J Reprod Med 1994 ; 39(10) : 761 – 4 . 13. Gidwani GP . Vaginal bleeding in adolescents. J Reprod Med
1984 ; 29(6) : 417 – 20 .
14. Diaz A , Laufer MR , Breech LL . Menstruation in girls and ado- lescents: using the menstrual cycle as a vital sign. Pediatrics 2006 ; 118(5) : 2245 – 50 .
15. Kadir RA , Economides DL , Sabin CA , Owens D , Lee CA . Fre- quency of inherited bleeding disorders in women with menor- rhagia. Lancet 1998 ; 351(9101) : 485 – 9 .
16. Claessens EA , Cowell CA . Acute adolescent menorrhagia. Am J Obstet Gynecol 1981 ; 139(3) : 277 – 80 .
17. Lukes AS , Kadir RA , Peyvandi F , Kouides PA . Disorders of hemostasis and excessive menstrual bleeding: prevalence and clinical impact. Fertil Steril 2005 ; 84(5) : 1338 – 44 .
18. Kujovich JL . von Willebrand's disease and menorrhagia: preva- lence, diagnosis, and management. Am J Hematol 2005 ; 79(3) : 220 – 8 .
19. Martin JA , Hamilton BE , Sutton PD , et al. Births: final data for 2004. Natl Vital Stat Rep 2006 ; 55(1) : 1 – 101 .
20. Janssen CA , Scholten PC , Heintz AP . Menorrhagia – a search for epidemiological risk markers. Maturitas 1997 ; 28(1) : 19 – 25 . 21. Speroff L , Fritz M . Clinical Gynecologic Endocrinology and
Infertility, 7th edn. Philadelphia : Lippincott Williams &
Wilkins , 2005 .
22. Buckler HM , Anderson DC . The perimenopausal state and incipient ovarian failure. In: Lobo RA , ed. Treatment of the Postmenopausal Woman. Philadelphia : Lippincott-Raven , 1996 : 11 – 23 .
31. Peterson HB , Jeng G , Folger SG, et al. The risk of menstrual abnormalities after tubal sterilization. U.S. Collaborative Review of Sterilization Working Group. N Engl J Med 2000 ; 343(23) : 1681 – 7 .
32. Kadir RA , Economides DL , Sabin CA , Pollard D , Lee CA . Assessment of menstrual blood loss and gynaecological problems in patients with inherited bleeding disorders. Haemophilia 1999 ; 5(1) : 40 – 8 .
33. Coulter A , Peto V , Doll H . Patients’ preferences and general practitioners’ decisions in the treatment of menstrual disorders.
Fam Pract 1994 ; 11(1) : 67 – 74 .
34. Vuorma S , Teperi J , Hurskainen R, et al. Correlates of women’s preferences for treatment of heavy menstrual bleeding. Patient Educ Couns 2003 ; 49(2) : 125 – 32 .
35. Coulter A , Peto V , Doll H . Influence of sex of general practi- tioner on management of menorrhagia. Br J Gen Pract 1995 ; 45(398) : 471 – 5 .
36. Warner P , Critchley HO , Lumsden MA, et al. Referral for men- strual problems: cross sectional survey of symptoms, reasons for referral, and management. BMJ 2001 ; 323(7303) : 24 – 8 . 23. Alberico S , Conoscenti G , Veglio P, et al. A clinical and epide-
miological study of 245 postmenopausal metrorrhagia patients.
Clin Exp Obstet Gynecol 1989 ; 16(4) : 113 – 21 .
24. Stewart EA . Uterine fibroids. Lancet 2001 ; 357(9252) : 293 – 8 . 25. West CP , Lumsden MA . Fibroids and menorrhagia. Baillières
Clin Obstet Gynaecol 1989 ; 3(2) : 357 – 74 .
26. Sulaiman S , Khaund A , McMillan N , Moss J , Lumsden MA . Uterine fibroids – do size and location determine menstrual blood loss? Eur J Obstet Gynecol Reprod Biol 2004 ; 115(1) : 85 – 9 . 27. Grodstein F , Goldman MB , Cramer DW . Body mass index and
ovulatory infertility. Epidemiology 1994 ; 5(2) : 247 – 50 . 28. Strauss JF , Lessey BA . The structure, function, and evaluation of
the female reproductive tract. In: Strauss JF , Barbieri RL , eds.
Yen and Jaffe’s Reproductive Endocrinology , 5th edn. Philadel- phia : Elsevier Saunders , 2004 : 213 – 53 .
29. Toriola AL , Mathur DN . Menstrual dysfunction in Nigerian athletes. Br J Obstet Gynaecol 1986 ; 93(9) : 979 – 85 .
30. Gentile GP , Kaufman SC , Helbig DW . Is there any evidence for a post-tubal sterilization syndrome? Fertil Steril 1998 ; 69(2) : 179 – 86 .
29 BACKGROUND
Abnormal uterine bleeding (AUB) is one of the common- est presenting symptoms and signs in gynecology, and has been recognized as such since ancient times. In centuries past, medical writings make it clear that the majority of women presenting to a physician with a menstrual bleeding problem did so with acute and severe uterine bleed- ing. 1 This symptom is variously described by medieval and ancient writers as excessive flooding, an overflowing of the courses, inordinate flowing, the immoderate flux, and so on. These physicians were dealing with a problem which was not only a serious social disturbance, but one which frequently led to the medical consequences of severe iron deficiency, anemia, and rarely, even death by exsanguinations. 2
It is only within the past half century or so that surgi- cal and medical management have become so effective and safe that lesser degrees of severity of abnormal uterine bleeding have gained much greater importance. In the 1960s and 1970s hysterectomy for benign gynecologic disease became very common in countries like the USA and Australia, and many of these women had presented with a complaint of heavy menstrual bleeding. Yet it soon became clear that individual women found it very diffi- cult to assess the volume of their menstrual loss, and had no absolute yardstick against which to make comparisons. 3 , 4 These women sometimes even had difficulty in assessing changes in volume of menstrual blood loss from one day to the next. 4 Nevertheless, when well counseled, many women were able to give a fairly accurate overall picture of their loss. 5
As the social status of women in westernized society has changed, and many young women compete with men for demanding professional jobs, there is decreasing occu- pational flexibility for the woman with severe, recurrent menstrual symptoms, whether they be heavy bleeding, prolonged bleeding, frequent bleeding, or menstrual pain.
The associated symptom complex accompanying heavy
bleeding, comprising headaches, extreme lethargy, drag- ging pelvic ache, backache, diarrhea, abdominal bloating, etc., compounds the social and occupational interference. 6 These symptoms still constitute the commonest cause of days lost from the female workforce, and young women are necessarily becoming much less tolerant of these phe- nomena. There is an increasing demand in many coun- tries for a ‘bleed-free’ existence from young women until such time as they start to plan for a family. 7
In these times of changing importance and tolerance of menstrual symptoms, there is still a real need for an understanding of the actual menstrual experience of each woman, which may lead to the initial menstrual complaint.
This should be put in social and medical context against a background of increasing precision in pelvic imaging and other investigations, 8 , 9 for detection of underlying causes, and an increasing range of options for medical and surgical management. In order to make good choices, a modern woman needs to have good information about what her menstrual experience means and what sequelae she may encounter if the symptoms progress.
OTHER FEATURES OF MENSTRUAL COMPLAINT
In some women the flow is lost from the uterus in a vari- able continuous discharge through the cervix, but in the majority it is lost in ‘gushes’ of varying volume. It seems that the uterine cavity tends to fill with blood, fluid, and cell debris while the myometrium is relaxed, and then when a contraction occurs, the contents are expelled into the vagina. Transvaginal ultrasound 9 can give a valuable picture of the changes in blood in the uterine cavity, if timed appropriately. Mostly, these little gushes are of a volume around 0.5–1 ml, but in women with excessive bleeding we have measured, on ultrasound scan, a uterine cavity volume of up to 28.5 ml immediately before a uterine contraction, and a ‘large gush’ around the vaginal