11.1
Introduction
Heavy menstrual bleeding (HMB) is a common condition that affects 20%–30% of women during their reproductive age and has a major impact on women’s quality of life.
The International Federation of Gynaecology and Obstetrics (FIGO) has defined HMB as “the women’s perception of increased menstrual volume regardless of regularity, frequency or duration.”
FIGO also define HMB as part of broader terminology of abnormal uterine bleeding (AUB) which includes intermenstrual bleeding (IMB) and postcoital bleeding (PCB).
FIGO definition of (AUB) includes:
- 1.
Disturbance of menstrual frequency and cycles shorter than 21 days are classified abnormal frequency of menses.
- 2.
Irregular menstrual bleeding—cycles when the onset of menses is unpredictable.
- 3.
Menstrual periods that exceed 8 days duration on a regular basis are classified as prolonged menstrual bleeding.
- 4.
HMB—describes increased menstrual volume regardless of regularity, frequency, or duration.
- 5.
Intermenstrual bleeding—episodes of bleeding that occur between normally timed menstrual periods.
11.1.1
Physiology of menstruation
- 1.
The average menstrual cycle length is 28 days and most women bleed for approximately 4–5 days associated with shedding of the superficial stratum functionalis of the endometrium.
- 2.
The endometrium is under the regulation of ovarian steroid hormones, mainly oestrogen and progesterone and their involvement in the monthly endometrial cycle is well established.
- 3.
Following menstrual shedding, the repair process is mainly under the influence of oestrogen and local haemostatic mechanisms.
- 4.
Mechanisms that interfere with the normal endocrine, paracrine or haemostatic functions of the endometrium as well as possibly any interference with myometrial contractility may cause HMB.
- 5.
Obesity influences the development and progression of menstrual problems,
- 6.
Obese women are three times more likely to suffer from menstrual abnormalities than women of a normal weight.
- 7.
Significant weight loss can restore normal menstruation pattern.
- 8.
AUB may be classified using the FIGO classification, using the PALM-COEIN paradigm. This acronym describes the aetiological basis of menstrual problems.
11.1.2
FIGO classification of AUB (PALM-COEIN)
The FIGO classification of AUB includes nine categories which are divided into two distinct subgroups:
- 1.
The PALM group: it consists of structural abnormalities that can be visualised using imaging techniques or diagnosed by histopathology.
- 2.
The COEIN group: it describes nonstructural disorders that cannot be imaged or diagnosed with histopathology ( Fig. 11.1 ).
Figure 11.1
FIGO-PALM-COEIN
11.2
Polyp
- 1.
Polyps are epithelial proliferations comprising variable vascular, glandular, fibromuscular and connective tissue components.
- 2.
Polyps may be asymptomatic and may be responsible for AUB.
- 3.
A survey of premenopausal women with endometrial polyps found that 82% reported AUB. In these women, obesity and hypertension were two risk factors,
- 4.
Another study also found that obese women had a significantly higher prevalence of polyps compared to normal BMI women,
- 5.
Obesity appears to be an important risk factor for the developing endometrial polyps,
- 6.
One potential mechanism for this is possibly higher levels of circulating oestrogens secondary to peripheral conversion of androgens by adipose tissue aromatase enzyme to oestrogens.
- 7.
Hence higher levels of both oestradiol and longer duration of exposure to unopposed oestrogens in obese women may have an augmented effect on the proliferative phase of endometrium.
11.3
Adenomyosis
- 1.
Adenomyosis is the presence of ectopic endometrial-like tissue within the myometrium.
- 2.
Unlike endometriosis, there appears to be a higher incidence of adenomyosis in obese women.
- 3.
The prevalence of adenomyosis varies widely, ranging from 5% to 70%.
- 4.
This is probably related to inconsistencies in the histopathologic criteria for diagnosis at hysterectomy specimens.
- 5.
MRI has a greater specificity and positive predictive value compared to transvaginal ultrasound and a greater ability to distinguish between adenomyosis and leiomyomas.
- 6.
This additional benefit of MRI over ultrasound scan is especially more relevant in obese population.
11.4
Leiomyoma
- 1.
Uterine fibroids (myomas, leiomyomas) are the most common benign tumours in women of reproductive age.
- 2.
Women who have incidentally diagnosed with small fibroids and are asymptomatic do not require treatment.
- 3.
Fibroids tend to be twice or even three times more common in non-white women as compared to other racial or ethnic groups.
- 4.
Heavy menstrual bleeding is the most common symptom of a fibroid uterus and multiple factors are thought to contribute:
- 5.
Increased endometrial surface area, increased uterine vascularity, impaired uterine contractility, and endometrial ulceration caused by submucosal fibroids may be possible mechanisms for menstrual symptoms.
- 6.
Location of uterine fibroids may contribute towards symptoms, with submucosal leiomyomas having a greater association with HMB, although objective evidence for this is limited.
- 7.
There is no consistent relationship between the size and location of fibroids and HMB.
11.5
Malignancy and hyperplasia
Obesity increases the risk of malignancy developing within an endometrial polyp,
- 1.
It has been estimated that 40% of all endometrial cancer is attributable to obesity, and that 86% of women with complex hyperplasia were obese.
- 2.
BMI is predictive of endometrial thickness on ultrasound scan and this is predictive of hyperplasia.
- 3.
The risk of endometrial cancer varied from an almost fourfold increase in women with a BMI> 25 kg/m 2 to an almost 20-fold increase in women with a BMI>40 kg/m 2 .
- 4.
A recent prospective study showed that bariatric surgery in women with BMI>40 can reverse atypical hyperplasia (Ref 24,25).
11.5.1
Coagulopathy
- 1.
Obese women are at increased risk of venous and arterial thromboembolism.
- 2.
There is increased procoagulant activity, impaired fibrinolysis, increased inflammation, endothelial dysfunction, and altered lipid and glucose metabolism in metabolic syndrome.
- 3.
Adipose tissue is known to produce several cytokines (known as adipokines), including Leptin, and adiponectin, tumour necrosis factor-α, and plasminogen activator inhibitor-1.
- 4.
Interleukin-6 has been implicated in mediating the link between abdominal obesity and venous thromboembolism.
- 5.
Approximately 13% of women with HMB have biochemically detectable systemic disorders of haemostasis, most often von Willebrand disease.
- 6.
Long-term anticoagulation may contribute to HMB/AUB.
11.6
Ovulatory dysfunction
- 1.
There is a strong association between menstrual cycle irregularities and anovulation with overweight and obesity,
- 2.
Compared to nonobese women, obese women had at least twofold greater odds of having an irregular cycle defined as >15 days between the longest and shortest cycle in the last 12 months,
- 3.
Contemporary studies from the United States and Australia that women with BMI >35 kg/m 2 had risk of long cycles compared to women with BMI 22–23 kg/m 2 , and these findings of independent of racial ethnicity.
- 4.
Ovulatory dysfunction can be often secondary to other disorders resulting in hormonal fluctuations such as:
- a.
polycystic ovary syndrome
- b.
hypothyroidism
- c.
hyperprolactinaemia
- d.
mental stress
- e.
obesity
- f.
anorexia
- g.
weight loss
- h.
or extreme exercise
- i.
hormonal fluctuations may be iatrogenic, caused by sex steroids or drugs that impact dopamine metabolism.
- a.
11.7
Endometrial
Due to a primary disorder of mechanisms regulating local endometrial haemostasis.
- 1.
Deficiencies in local production of vasoconstrictors (endothelin-1 and prostaglandin F2α).
- 2.
and/or accelerated lysis of endometrial clot because of excessive production of plasminogen activator, in addition to increased local production of vasodilators (prostaglandin E2 and prostacyclin I2).
Primary endometrial disorders (may be a manifestation of deficient mechanisms of endometrial repair):
- 1.
may be secondary to endometrial inflammation or infection (Chlamydia Trachomatis).
- 2.
abnormalities in the local inflammatory response and/or aberrations in endometrial vasculogenesis:
- a.
There are minimal data available in the literature on the influence of obesity on the volume of menstrual blood loss.
- b.
However raised BMI is associated with poor efficacy of hormonal contraception suggesting an effect of obesity on bioavailability or action of steroids.
- a.
11.7.1
Iatrogenic
- 1.
Unscheduled bleeding that occurs during the use of sex steroid therapy is termed “breakthrough bleeding (BTB).”
- 2.
Many episodes of unscheduled bleeding/BTB are related to compliance issues or reduced circulating hormone levels because of enhanced hepatic metabolism:
- a.
missed, delayed, or erratic use of anticonvulsants;
- b.
certain antibiotics (e.g., rifampacin and griseofulvin); and
- c.
cigarette smoking.
- a.
- 3.
Vaginal spotting/bleeding in the first 3–6 months of the use of LNG-IUS.
- 4.
Tricyclic antidepressants (amitriptyline and nortriptyline) and phenothiazines impact dopamine metabolism by reducing serotonin uptake, resulting in reduced inhibition of prolactin release, leading to anovulation and AUB.
- 5.
The use of anticoagulant drugs (warfarin, heparin, and low molecular weight heparin) leads to impaired formation of an adequate “plug” or clot within the vascular lumen. Not yet classified (AUB-N).
Not yet classified group:
Clinical entities maybe associated with or contribute to AUB/HMB, such as:
- 1.
chronic endometritis
- 2.
arteriovenous malformations
- 3.
bleeding from a caesarean section scar defect
- 4.
isthmocoele
- 5.
myometrial hypertrophy.
However, there is limited evidence to support this hypothesis.
Obesity in the absence of polycystic ovary:
- 1.
Obesity independently increases hyperandrogenism, hirsutism, insulin resistance and infertility.
- 2.
The presence of insulin resistance predicts a thicker endometrium on ultrasound scan.
- 3.
A high BMI is positively associated with the thickness of the endometrium in the absence of PCO.
- 4.
Obesity has been associated with increased uterine blood flow as measured by Doppler uterine artery pulsatility index.
11.8
Structured history taking in women with AUB
A structured history should be taken to establish a cause and diagnosis.
It should include the nature of bleeding, the impact of bleeding on quality of life and related symptoms such as pelvic pain, postcoital bleeding and intermenstrual bleeding.
Symptoms of anaemia such as tiredness, fatigue, lethargy and breathlessness should be elucidated. A coagulation disorder may be considered by history of excessive bleeding since menarche, and/or history of postpartum haemorrhage, and surgery related bleeding, such as dental extraction, as noted in Table 11.1 are identified.
