Abnormal uterine bleeding can occur when a woman experiences a change in menstrual loss, or the degree of loss or vaginal bleeding pattern differs from that experienced by the age-matched general female population AUB is not restricted to menstrual bleeding that is abnormally heavy, but includes bleeding that is abnormal in TIMING

1. Understanding
Abnormal Uterine
Bleeding (AUB)
What to do with troublesome Ms
Menses?
DR. THIAGU CHIDAMBARAM
OBSTETRICIAN & GYNAECOLOGIST
SARAWAK GENERAL HOSPITAL

2. Contents
• Abnormal uterine
bleeding:
– Definition & classification
• Abnormal uterine
bleeding – Ovulatory
disfunction:
– Definition
– Prevalence
– Symptoms
– Consequences and burden
• Normal menstrual
physiology
• The hypothalamic-
pituitary-ovarian axis
(HPO axis)
• AUB-O and the menstrual
cycle
• Forms of AUB-O
• Diagnosis of AUB-O
• Treatment of AUB-O

3. What is
abnormal uterine bleeding (AUB)?
• Abnormal uterine bleeding can occur when a woman
experiences a change in menstrual loss, or the degree of
loss or vaginal bleeding pattern differs from that
experienced by the age-matched general female
population1
• AUB is not restricted to menstrual bleeding that is
abnormally heavy, but includes bleeding that is
abnormal in TIMING2
1. National Institute for Health and Clinical Excellence 2007. Heavy menstrual bleeding [CG24] London: National Institute for Health and Clinical Excellence.
2. Munro MG, et al. Int J Gynecol Obstet 2011; 113: 3-13.

4. FIGO classification system for AUB
Basic classification system1
1. Munro MG, et al. Int J Gynecol Obstet 2011; 113: 3-13.
The basic system comprises:1
Four categories that are defined by visually objective structural criteria
(PALM: polyp; adenomyosis; leiomyoma; and malignancy and hyperplasia)
Four categories that are unrelated to structural anomalies
(COEI: coagulopathy; ovulatory dysfunction; endometrial; iatrogenic)
One category reserved for entities that are not yet classified (N)
The leiomyoma category (L) is subdivided into patients with at least 1 submucosal myoma
and those with myomas that do not impact the endometrial cavity
Polyp
Adenomyosis
Leiomyoma
Malignancy & hyperplasia
Submucosal
Other
Ovulatory dysfunction
Endometrial
Iatrogenic
Not yet classified
Coagulopathy
Structural
Functional

5. Birth 10 20 30 40 50 60
Likely causes of AUB vary by patient age
Adapted from Pelea-Nagtalon S. Vignette approach in addressing menstrual disorders.
Oestrogen
withdrawal
Anovulation Central, intermediate, gonadal
Functional Blood dyscrasia, hypothyrodism, luteal
dysfunction
Iatrogenic Anticoagulation, contraception (hormonal
intrauterine), haemodialysis
Pregnancy Abortion, ectopic, placental polyp, retained
products, trophoblastic disease
Uterine Infection, structural (fibroids, hyperplasia,
neoplasia, polyps)
Foreign body
Infection
Sarcoma botryoides
Ovarian tumour
Trauma
Blood dyscrasia
Hypothalamic immaturity
Inadequate luteal function
Psychogenic (including anorexia and bulimia)
Carcinoma (cervical, uterine)
Climacteric
Polyps
Atrophic vaginitis
Carcinoma (uterine, ovarian)
Oestrogen replacement

6. What is
dysfunctional uterine bleeding (DUB)?
• Abnormal uterine bleeding in premenopausal women not
caused by pelvic pathology, systemic disease or pregnancy1
• Abnormal vaginal bleeding that occurs during a menstrual
cycle that produced no egg (ovulation did not take place).
The occurrence of irregular or excessive uterine bleeding in
an absence of pregnancy, infection, trauma, new growth or
hormone treatment2
1. Muneyyirci-Delale O, et al. Int J Womens Health 2010; 2: 297-302.
2. National Institute for Health and Clinical Excellence 2007. Heavy menstrual bleeding [CG24] London: National Institute for Health and Clinical Excellence.

7. Prevalence of DUB
• DUB accounts for around 20% of gynecology office
visits1
– Heavy menstrual bleeding accounts for 5% of visits to
GPs
• Between 9 and 30% of reproductive-aged women
have menstrual irregularities requiring medical
evaluation3
• Approximately 35–55% of women in late
reproductive age suffer
from DUB4
1. Muneyyirci-Delale O, et al. Int J Womens Health 2010; 2: 297-302.
2. Santer M, et al. J Clin Epidemiol 2005; 58: 1206-1212.
3. Dangal G. Internet J Gyne Obs 2005; 4(1).
4. Tatarchuk TF, et al. Women’s Health 2009; N6 (42).

8. So now with the new classification :
DUB = AUB-O (abnormal uterine bleeding –
ovulatory dysfunction)

9. What are the symptoms
of AUB-O?
• Patients may present with symptoms that include:1
– Fatigue
– Pelvic pain and cramps
– Disordered menstrual bleeding
• Old Terminology of menstrual patterns associated
with DUB:
– Excessive flow (menorrhagia)
– Irregular cycles (metrorrhagia)
– Cycle length <21 days (polymenorrhoea)
– Excessive flow AND irregular cycles
(menometrorrhagia)
1. Frick KD, et al. Women’s Health Issues 2009; 19: 70-78.

10. Consequences and burden
of DUB
• Luteal insufficiency, anovulation and repetitive
episodes of heavy menstrual bleeding can
result in more serious consequences:
– Iron deficiency anaemia1
– Miscarriage2
– Endometrial hyperplasia and endometrial
carcinoma3
• Affects women’s health both medically and
socially1
1. Pitkin J. Brit Med J 2007; 334(7603): 1110-1111.
2. Daya S. Maturitas 2009; 65(S1); S29-S34.
3. Takreem A, et al. J Ayub Med Coll Abbottabad 2009; 21(2): 60-63.

11. Normal menstrual
physiology1
Oestrogen levels increase
gradually during the follicular
phase and fall just before
ovulation. Levels are maintained
during the luteal phase and fall
before menstruation
Progesterone levels increase
during the luteal phase and fall
sharply just before menstruation
1. Chrousos G, et al. Ann Intern Med 1998; 129: 229-240.

12. Normal menstrual function and the
hypothalamic-pituitary-ovarian axis
Menstrual cycle events are controlled by hormones
secreted by three key organs known as the
hypothalamic-pituitary-ovarian axis (HPO axis):1
• The hypothalamus in the brain secretes GnRH
• The pituitary gland just below the
hypothalamus secretes:
– FSH necessary for the development of the
immature ovum (the primordial follicle in
the ovary)
– LH which triggers ovulation
• The ovary secretes the steroid hormones
oestrogen and progesterone
1. Dangal G. Internet J Gyne Obs 2005; 4(1).
Ovaries
ProgesteroneOestrogen
Secretory
(Luteal)
Phase
Proliferative
(Follicular)
Phase
Hypothalamus
Anterior Pituitary
GnRH
FSH/LH
FSH, follicle stimulating hormone; GnRH, gonadotrophic releasing hormone;
LH, luteinising hormone

13. Normal menstrual function and the
hypothalamic-pituitary-ovarian axis1
The interplay of hormones in the HPO axis is regulated by a
feedback mechanism:
• The secretion of FSH and LH from the pituitary gland is
under the control of GnRH from the hypothalamus
• The hypothalamus in turn is controlled by the levels of
the ovarian steroid hormones oestrogen and
progesterone in the blood by means of a feedback
mechanism
• The hypothalamus may also be affected by external
factors e.g. stress
1. Dangal G. Internet J Gyne Obs 2005; 4(1).

14. DUB and the
menstrual cycle
• DUB can occur at any time between
menarche and menopause in
ovulatory or anovulatory cycles1
• Pathophysiology of DUB:
– Anovulatory: hypothalamic-pituitary-
ovarian axis
– Ovulatory: endometrial molecular
mechanisms
1. Chen BH, Giudice LC. West J Med. 1998; 169(5): 280-4.

15. Anovulatory DUB
• Deviations from the normal cycle due to disruptions in the balance of the HPO axis
– When ovulation does not occur, the effects of oestrogen are unopposed, leading to
continuous proliferation of the endometrium1
– Proliferation without periodic shedding causes the endometrium to outgrow
its blood supply
– This leads to irregular shedding of the endometrium1
• Bleeding episodes are irregular, prolonged or excessive
• Far more frequent than ovulatory DUB1
• Common in pubertal and perimenopausal periods2
1. Brenner PF. Am J Obstet Gynaecol 1996. 175(3 Pt 2): 766-9.
2. Pitkin J. Brit Med J 2007; 334(7603): 1110-1111.

16. Ovulatory DUB
• Defects in the control
mechanisms of menstruation1
– Ovulatory DUB is secondary to
defects in local endometrial
hemostasis
– Bleeding occurs cyclically
• Far less frequent than
anovulatory DUB2
1. Pitkin J. Brit Med J 2007; 334(7603): 1110-1111
2. Brenner PF. Am J Obstet Gynaecol 1996. 175(3 Pt 2): 766-9.

17. Forms of DUB: acute, chronic
and intermenstrual bleeding
1. National Institute for Health and Clinical Excellence 2007. Heavy menstrual bleeding [CG24] London: National Institute for Health and Clinical Excellence.
2. Munro MG, et al. Int J Gynaecol Obstet 2011; 113: 3-13.
Heavy menstrual bleeding Intermenstrual bleeding
Acute
Chronic
An episode of heavy bleeding that, in the opinion of the clinician, is of sufficient quantity to require immediate intervention
to prevent further blood loss2
Excessive menstrual blood loss which interferes with
a woman’s physical, social, emotional and/or material
quality of life1
Bleeding that occurs between clearly defined cyclic and
predictable menses2
Bleeding from the uterine corpus that is abnormal in volume, regularity, and/or timing, and has been present for the
majority of the past 6 months2

18. Diagnosis of DUB:
a ‘diagnosis of exclusion’1
1. Pitkin J. Brit Med J 2007; 334(7603): 1110-1111.
2. Qi Y. Chin J Obstet Gynecol 2009; 44(3). [Translated from Chinese].
3. National Institute for Health and Clinical Excellence 2007. Heavy menstrual bleeding [CG24] London: National Institute for Health and Clinical Excellence.
Diagnosis requires
Thorough medical history2,3 Auxiliary examinations2,3Physical examination2,3

19. Diagnosis of DUB:
a ‘diagnosis of exclusion’1
1. Pitkin J. Brit Med J 2007; 334(7603): 1110-1111.
2. Qi Y. Chin J Obstet Gynecol 2009; 44(3). [Translated from Chinese].
3. National Institute for Health and Clinical Excellence 2007. Heavy menstrual bleeding [CG24] London: National Institute for Health and Clinical Excellence.
Diagnosis requires
Thorough medical history2,3 Auxiliary examinations2,3Physical examination2,3
Including:
• Patient’s age
• Menstrual history
• Marital history & fertility
• History of endocrine diseases or
coagulation disorders
• History of recent medication
Look for positive signs of:
• Anaemia
• Hypothyroidism
• Hyperthyroidism
• Polycystic ovary syndrome (PCOS)
• Haemorrhagic disorders
Gynaecologic examination to rule out:
• Vaginal, cervical or uterine diseases
• Complete blood count (rule out
anaemia/thrombocytopenia)
• Coagulation function tests
• Pregnancy tests
• Pelvic ultrasound (rule out uterine
lesions)
• Measurement of basal body
temperature (confirm ovulation &
rule out luteal insufficiency)
• Determination of hormone levels

20. Medical treatments: key points
• Non-hormonal therapies are considered first line treatments1
• The aim of treatment is to
1) prevent excessive menstrual bleeding and
2) regulate menstrual bleeding2
• Factors to consider when choosing a treatment:1
– Degree of bleeding (acute or chronic)
– Age-related factors
– Need for contraception
– Adverse effect profile
1. Pinkerton JV. Menopause 2011; 18: 453-461.
2. Hickey M, et al. Progestogens with or without oestrogen for irregular uterine bleeding associated with anovulation.
Cochrane Database of Systematic Reviews 2012, Issue 10. Art.No.: CD001895. DOI: 10.1002/14651858.CD001895.pub3.
3. Qi Y. Chin J Obstet Gynecol 2009; 44(3). [Translated from Chinese].

21. Treatment goals for managing the
symptoms of DUB
Excessive flow
Symptoms of menstrual bleeding
Normalisation of
menstrual bleeding amount
Management of symptoms
Irregular cycles
Improvement in regularity and
duration of menstrual cycle
Cycle length <21 days
Normalisation of
menstrual cycle length
+
Improvement in endometrial
characteristics

22. Hormonal treatments for DUB1
• Progestogens:
(e.g. progesterone, dydrogesterone, medroxyprogesterone acetate [MPA])
– Suitable for patients with a haemoglobin level of greater than 80g/L and stable vital signs
• Compound short-acting oral contraceptives:
(e.g. desogestrel-ethinyl estradiol, gestodene-ethinyl estradiol, compound cyproterone acetate)
– Indicated for long and severe anovulatory bleeding
• Synthetic progestogens:
(e.g. levonorgestrel, norethisterone)
– Can cause thinning of the uterine lining, thus reducing severity of bleed
1. Qi Y. Chin J Obstet Gynecol 2009; 44(3). [Translated from Chinese].

23. Clinical Guidelines
support the prescription of progestogens
• “Progestogen therapy administered for
21 days of the menstrual cycle results
in a significant reduction in menstrual
blood loss, although they have been
found to be ineffective unless taken at
high doses”1
Ministry of Health, Malaysia
1. Ministry of Health, Malaysia 2004. Management of Menorrhagia [MOH/P/PAK/95.04]. Putrajaya: Ministry of Health.
2. Qi Y. Chin J Obstet Gynecol 2009; 44(3). [Translated from Chinese].

24. Cycle regulation with natural
progesterone and synthetic progestins1
Properties Dydrogesterone Progesterone
Testosterone &
19 nortestosterone
derivatives
Progesterone
derivatives
Blocking of ovulation –* + + +
Oestrogenic – ± + –
Androgenic – – + +
Masculinisation of foetus – – + +
Relaxation of uterine tissue + + – ±
Adrenal atrophy – – + +
Thermogenicity – + + +
Blood clotting – – + +
Blood lipids – – + –
+ effect; – no effect; ± equivocal; * at normal dosage
“natural”
Progesterone
Lynestrenol 5 mg
Norethisteron 5 mg
Medrogeston 5 mg
MPA 10 mg
Levonorgestrel
1. Schindler AE, et al. Maturitas 2009; 46(S1): 7-16.

25. Improvement in
endometrial characteristics
Progestogen actions on the endometrium
• Stops oestrogen-induced growth of the
endometrium
• Stabilises endometrial vasculature and
blocks unrestricted vessel growth1
• Initiates the clotting cascade1
• Haemostatic and anti-fibrinolytic action
(PAI-1 pathway)1
• Inhibits matrix metallo-proteinase
1. Lockwood CJ. Menopause 2011; 18(4): 408–411.

26. Process for prescription:
patient-specific considerations
• Diagnosis and choice of treatment depends on many
patient-specific considerations, e.g:
– What age is the patient?
(causes of AUB/DUB vary with age)
– Is the patient trying to conceive? Or do they require
contraception? (certain treatments block ovulation)
– Does the patient have any underlying medical conditions?
(e.g. haematologic or coagulation disorders)
– Is the patient a smoker? (smokers have an increased risk
of venous thrombosis with low-dose oral contraceptives)1
1. Kemmeren JM, et al. Brit Med J 2001; 323(7305):131.