• 1.
  

  a) F b) T c) T d) F e) F

Cervical cancer can occur in all settings but is more common in resource restricted settings due to inadequate screening programs. Screening and treatment are effective. Prophylactic vaccines are available to many resource restricted countries but this does not negate the importance of screening as the effects of vaccines will only be seen in years to come.

• 2.
  

  a) F b) F c) F d) T e) F

Vaginal packing is not definitive management but rather a temporary measure to tamponade and stop bleeding prior to definitive treatment. Uterine artery embolisation is not definitive management of cervical cancer, but rather a means to stop bleeding as an emergency. Packing works by direct pressure and fibrin pro-coagulant impregnation does not exist. Radiation treatment is often the next approach once acute bleeding has settled. All cervical cancers who have a torrential bleed, do not automatically become palliative. Treatment depends on clinical stage.

• 3.
  

  a) F b) T c) F d) F e) F

It is more common in postmenopausal women but can occur in younger women with risk factors. Studies have shown that 14% of women with type 1 uterine cancer are premenopausal and 5% are less than age 40. Approximately 50% of these cancers can be attributed to obesity alone. There has been a decline in the use of hormonal treatment over the last decade due to fears of breast cancer etc. Reporting for cancers has been good for many years especially in developed countries and the increase appears to be real. Whilst Tamoxifen has a stimulatory effect on the endometrium it usually causes benign polyps and hyperplasia – it is actually a rare cause of secondary cancer.

• 4.
  

  a) F b) F c) F d) T e) T

GTN can occur in any age group, although more common in women of reproductive age, the rarer placental site trophoblastic and epithelioid trophoblastic histological subtypes may occur years after a pregnancy. Persistent bleeding after one evacuation should be investigated. If a pregnancy of unknown location persists for a long time then alternative secretion needs to be considered.

• 5.
  

  a) T b) T c) F d) T e) T

SPRMs are known to reduce bleeding due to fibroids and sometimes DUB. The other causes need the primary problem rectified.

• 6.
  

  a) F b) F c) F d) F e) T

Focal intrauterine lesions such as endometrial polyps and submucous fibroids are best diagnosed when the uterine cavity is distended with fluid. Systematic accuracy reviews have shown that hysteroscopy is more accurate than ultrasound scan or saline infusion sonography for the diagnosis of endometrial polyps. Polyp fragments can be detected on histological analysis of endometrial biopsy specimens but sampling of the endometrial surface is incomplete with such approaches. Recent evidence from an RCT of women with postmenopausal bleeding suggests that blind endometrial sampling misses endometrial polyps. 3D ultrasound is a welcome technical advance in ultrasonography but more studies are needed to demonstrate its effectiveness over and above current diagnostic tests for endometrial abnormalities. Instrumentation of the uterine cavity and distension induces pain whether during saline infusion sonography or hysteroscopy. Instillation pressures should be kept to a minimum to minimise pain. Hysteroscopy has been shown to the most discriminative test for detecting and excluding the presence of endometrial polyps in systematic reviews of diagnostic accuracy.

• 7.
  

  a) F b) F c) F d) F e) T

The PALM-COEIN classification of causes for heavy menstrual bleeding includes polyps (denoted AUB-P). However, polyps remain an enigma and the natural history is not well understood. Thus, whilst polypectomy is a generally straight forward procedure, mandatory removal cannot be advocated especially where there are medical co-morbidities. Medical treatments have not been shown to specifically reduce the likelihood of endometrial polyp formation but are effective for treating symptoms of abnormal uterine bleeding. The accuracy of blind sampling for diagnosis of endometrial abnormalities is now being questioned and as a treatment is outdated because focal anomalies are missed or incompletely removed and risk inadvertent uterine trauma. Recent RCT data suggests that endometrial polypectomy is indicated in women with post-menopausal bleeding to diagnose endometrial hyperplasia or cancer but does not reduce the risk of recurrent presentations with further episodes of vaginal bleeding.

• 8.
  

  a) F b) F c) F d) T e) T

Blind procedures will sample only a fraction of the endometrium and will miss or incompletely remove focal lesions such as endometrial polyps. Moreover uterine trauma is more likely. The effectiveness of polypectomy in resolving abnormal bleeding symptoms does not differ whether polyps are removed in an inpatient or outpatient setting. However, the outpatient setting is more likely to fail to remove polyps. Monopolar electrical circuits are more likely to result in hyponatraemia secondary to fluid overload. When electrosurgery is used, bipolar systems should be employed. Evidence from randomised controlled studies supports the use of tissue removal systems rather than conventional miniature mechanical and electrosurgical technologies. Hysteroscopic surgery minimises uterine trauma and facilitates complete removal of endometrial lesions.

• 9.
  

  a) T b) T c) F d) T e) T

Qualitative research shows that the immediacy and convenience of outpatient treatment is highly valued by women. A recent randomised controlled trial reported 4 cases of uterine perforation in the inpatient general anaesthetic group (one of which resulted in bowel trauma) compared with none in the outpatient group. One in five outpatient procedures fail to completely excise and retrieve endometrial polyps from the uterine cavity compared to one in 14 inpatient procedures. No statistical difference in the resolution of abnormal uterine bleeding symptoms (heavy menstrual bleeding, intermenstrual bleeding, postmenopausal bleeding) were observed between outpatient and inpatient settings in a recent, large, multicentre randomised controlled trial. An economic analysis conducted alongside a randomised controlled trial has shown that the outpatient setting for endometrial polypectomy is cost-effective compared with the inpatient, general anaesthetic setting.

• 10.
  

  a) T b) F c) F d) T e) F

The majority of women with postmenopausal bleeding with an endometrial thickness >15mm have cancer. An endometrial thickness >10mm can signify cancer, however, if no other suspect imaging features or risk factors for cancer are present, hyperplasia or polyps are more probable causes. An interrupted endo-myometrial junctional zone is a sign that may indicate cancer. The interruption is often best identified by slight pushing of the probe. The JZ is usually not interrupted in hyperplasia, but may be interrupted in adenomyosis. Doppler findings of a small single or double vessel with regular branching is a characteristic finding of a polyp. Cancers features include multiple, large vessels and confluent vessels may give rise to “colour-splash”-flow. Up to 13% of polyps with benign features may be malignant. Moreover, polyps, hyperplasia and endometrial cancer often coexist. Endometrial histology is required when the endometrial thickness is >4–5mm.

• 11.
  

  a) T b) F c) F d) F e) T

Typical ultrasound features of myomas in the myometrium are a well-defined, round lesion. Shadowing is often present at the edge of myomas (edge shadows) or internal (fan shaped shadowing). Features of leiomyosarcomas includes a single large lesion with a heterogenic mixed echostructure. At least two of the characteristics of adenomyosis needs to be present to give a diagnosis of adenomyosis. Characteristics include asymmetry of uterine walls, a globally enlarged uterus, ill-defined myometrial mass, anechogenic cysts, small anechoic lacunae, linear striations and buds, irregular endometrial outline. Transvaginal ultrasound is first choice. Sonohysterography may be needed to determine the impact of myomas on the endometrial cavity. The numbers of myomas with diameter >1–1.5 cm should be counted, measured and mapped according to location and site (0-8). 3D-Ultrasonography may be advantageous in evaluation of a few myomas. In the presence of multiple myomas and when minimally invasive treatment options are planned, MRI may enable mapping of more myomas. The accuracy of measurements of 1-4 myomas are no more accurate on MRI than TVS. Small dimensional hysteroscopes are not optimal in the presence of bleeding and larger pathology, but can be used to remove small polyps and myomas.

• 12.
  

  a) T b) T c) F d) T e) T

Dysfunctional uterine bleeding results from immaturity of the hypothalamus-hypophysis-ovary axis, which is frequent in the adolescent. The causes of morphological alterations, polyps, and myomas are more frequent during the climacteric. Besides the morphological causes, in the perimenopause, endometrial polyps are more common and there may be some alterations due to anovulatory cycles, even reaching hyperplasia. In this age group, the presence of vaginal bleeding requires an evaluation of the uterine cavity to exclude the presence of hyperplasia or neoplasia, since the most frequent complaint of patients in this age group with endometrial cancer is AUB. During the post menopause, in the presence of hypoestrogenism, the most probable cause of AUB is endometrial atrophy.

• 13.
  

  a) T b) T c) T d) T e) T

All these causes are related to AUB.

• 14.
  

  a) F b) T c) T d) T e) F

Only submucosal myomas or those that distort the cavity are related to AUB, and even in its presence, other causes may be responsible for the bleeding. Magnetic resonance is indicated in uteri with more than four myomas and volume greater than 375 cm ³ and in patients for whom preservation of the uterus is indicated. Since endometrial cancer is more frequent in the post menopause and has AUB as its primary complaint, investigation of the uterine cavity is mandatory. Bleeding of the myoma is generally related to menstruation, increasing the flow or prolonging its duration. Intermenstrual bleeding is more related to endometrial diseases. In postmenopausal women with bleeding, with or without a uterine myoma, investigation of the uterine cavity is mandatory before surgery, since endometrial cancer must be excluded.

• 15.
  

  a) T b) T c) F d) F e) F

Worldwide the most common cause of anaemia is ID accounting for approximately 50% of cases. Women who have hypothalamic amenorrhoea may have a reduced iron intake from cereals and red meat and obese women presenting with infrequent periods or amenorrhoea produced pro-inflammatory cytokines from obese adipose tissue. This elevates hepcidin levels resulting in reduced iron absorption increasing the risk of ID/IDA. The opposite is true. Lowering the levels of hepcidin increases iron absorption from the gut. Ferroportin is a transmembrane protein which exports iron into the blood from enterocytes and macrophages. Serum ferritin levels below 15 μg/L are consistent with a diagnosis of iron deficiency. Sensitivity is improved from 25 to 92% using a cut-off of 30 μg/L and specificity remains high at 98%.

• 16.
  

  a) F b) F c) T d) T e) T

Transferrin saturation is a measure of functional iron available for red cell production. Although the rise in haemoglobin is more rapid initially, by 12 weeks, parenteral and oral iron therapy result in similar levels of haemoglobin. The tannins in tea will decrease the absorption of oral iron from the gut. Ferric iron is less soluble than ferrous iron in physiological pH environments. However ferric polymaltose complex stabilized by polymaltose has similar bioavailability to ferrous salts but its uptake is actively rather than passively controlled.

• 17.
  

  a) F b) F c) T d) F e) F

Although greater than or equal to 80 ml mean blood loss has historically been used as the definition of heavy menstrual bleeding (previously termed “menorrhagia”) (based on population studies conducted in Sweden in 1966), NICE did not use this in their definition of heavy menstrual bleeding (HMB). Nearly 2/3rds of women presenting for evaluation and treatment for heavy menstrual bleeding would not meet this objective blood loss criterion. The pictorial bleeding assessment chart has been widely used in research to reflect the amount of blood lost during the menstrual period, with a higher score reflecting greater loss. However, this score and scale were not used in the NICE definition of heavy menstrual bleeding. Given the increased emphasis on impact of bleeding symptoms on quality of life as the driver for women’s experiences with heavy menstrual bleeding and healthcare seeking for this problem, quality of life was prominently included in the NICE definition of heavy menstrual bleeding. The Aberdeen Menorrhagia Severity Scale is a good quality bleeding-specific quality of life questionnaire that has been used widely in clinical research. However, it has not been validated for use in clinical care and was not included in the NICE definition of heavy menstrual bleeding. There is no definition of timings for change of sanitary protection – it is what interferes with normal life that matters and that will vary from woman to woman.

• 18.
  

  a) F b) F c) F d) T e) T

Although reduction in bleeding (which can be objectively measured for research purposes) is usually desirable for patients, using only this objective measurement fails to capture the patient experience and bleeding-related quality of life. Therefore, it can be argued that this is not the most important outcome to assess. General health (as opposed to symptom or disease focused) quality of life questionnaires have been used commonly across studies evaluating women with heavy menstrual bleeding. However women with heavy menstrual bleeding have reported that some of the questions are difficult to answer because heavy menstrual bleeding is an intermittent symptom and it is typically not life-threatening. General quality of life instruments can be helpful when used in combination with condition or disease specific questionnaires. No set of outcome measures or single instrument has been considered “standard” for use across all studies on treatment of heavy menstrual bleeding. Recent systematic reviews on heavy menstrual bleeding have highlighted the lack of consistency of outcome measurement across studies as a challenge limiting the interpretability of the body of literature and the ability to generate consensus on the relative effectiveness of treatment options. In the future, this may be addressed by the CROWN Initiative: Core Outcomes In Women’s and Newborn Health. Consistent outcome reporting across studies will aid in the interpretability of study results and the feasibility of combining data across studies for either traditional meta-analyses or patient-level data meta-analyses. Studies have suggested that disease/symptom-specific patient reported outcome measures should be used to evaluate women with heavy menstrual bleeding because symptoms are not generally constant and symptoms are distressing but not necessarily life-threatening. Although no one instrument has been considered “standard” for use across all studies on treatment of heavy menstrual bleeding, several good quality questionnaires (the AMSS, the MMAS, the MIQ, and the MBQ) are available and can be used to evaluate symptom impact. Cost-effectiveness measures are always an important component for any study relating to QoL.

• 19.
  

  a) F b) F c) T d) T e) F

Although 6 months and 1 year may be good time intervals for assessing some outcomes, the timing and interval of outcome assessment needs to be tailored to the problem of interest and selected by the clinician using the patient-reported outcome measure. No standard time intervals have been defined for the clinical assessment of heavy menstrual bleeding. There are relative advantages and disadvantages of different mechanisms of questionnaire administration (self-completed, interviewer completed, device completed). The best mechanism of questionnaire administration is dependent on the subject matter, the types of questions included, the purpose of the questionnaire and the population. Clinical care situations are unique and patient-reported outcome measures can be used in a variety of ways. It is the job of the clinician to determine the goals of collecting patient reported outcomes (screen for problem, aid in narrowing differential diagnosis, follow symptoms over time, facilitate patient-centred care) and to choose the appropriate outcome measure to meet the defined goal. Sharing results with patients is an option when collecting patient reported outcome measures and in some circumstances facilitate patient participation in management of their symptom, however it is not mandatory. Most studies report generalised population information.

• 20.
  

  a) F b) F c) F d) F e) T

The patient’s self-reporting is the single most important factor included in the FIGO system.

• 21.
  

  a) T b) F c) F d) F e) F

The PALM-COEIN system is indeed a method of categorizing the results of investigation of women with abnormal uterine bleeding in the reproductive years. It is not appropriate for postmenopausal women and is not in itself a diagnostic aid.

• 22.
  

  a) T b) F c) T d) F e) F

  
  
• 
  

  PALM-COEIN Classification Nomenclature

  
  
  
  
  • •
    

    P Polyps

    
    
  • •
    

    A Adenomyosis

    
    
  • •
    

    L Leiomyoma

    
    
  • •
    

    M Malignant and premalignant

    
    
  • •
    

    C Coagulopathies

    
    
  • •
    

    O Ovarian dysfunction

    
    
  • •
    

    E Endometrial dysfunction

    
    
  • •
    

    I Iatrogenic

    
    
  • •
    

    N Not otherwise classified

  
  
  
  
• 23.
  

  a) F b) F c) T d) T e) F

Both contrast hysterosonography and hysteroscopy have been shown to have high sensitivity and specificity for structural abnormalities. Biopsy and D&C are less accurate and CT scan has been superseded by the diagnostic accuracy of MRI in the pelvis.

• 24.
  

  a) F b) T c) T d) F e) F

Uterine fibroids are very common, present in 70-80 % of all women by age 50, they are the leading cause of hysterectomy (400,000 every year in the USA), the cost of all procedures required may be extremely significant (34 billion US $ yearly in the USA), notwithstanding the fact that the main complication of uterine fibroids, excessive uterine bleeding, is responsible for a severe alteration of quality of life. Fibroids are more frequent and more severe in women of African origin. Classically, oestrogen is considered as the leading growth signal. These are benign smooth muscle cell tumours, often harbouring recurrent chromosomal rearrangements.

• 25.
  

  a) T b) T c) F d) T e) F

The key issue has been the interpretation of the endometrial changes observed during treatment. These are now widely recognized as PAECs: PRM Associated Endometrial Changes. The endometrial histology shows altered glandular architecture including extensive glandular epithelial dilatation. The epithelium appeared essentially inactive with rare mitoses. Mild reversible thickening rarely occurred.

• 26.
  

  a) T b) F c) F d) T e) F

The changes proved to be reversible following cessation of therapy and were associated with no sign of epithelial or stromal proliferation. Curiously enough, it is now recognised that PAECs can also be observed in a significant number of untreated patients. Their significance is unknown.

• 27.
  

  a) T b) T c) F d) F e) F

The mechanism of cessation of bleeding is not completely understood, it is mainly associated with changes in the appearance of capillaries in the endometrium, and of spiral arteries with thick muscular walls, and some interference with angiogenesis. The molecular basis of this effect awaits clarification.

• 28.
  

  a) T b) T c) F d) F e) T

The mechanism of the decrease in fibroid size is clearly a consequence of the interruption of the growth signal from progesterone. This effect of progesterone has been neglected for many years, and as a matter of fact is clearly proven by the use of anti-progestins such as PRMs. This involves multiple molecular pathways including apoptosis and other extracellular matrix signalling. The signalling pathway used by PRM to decrease individual fibroid size includes growth factor pathways such as TGF ß signalling.

• 29.
  

  a) F b) T c) T d) T e) T

Hepcidin is an acute-phase reactant which is primarily synthesised in the liver. In response to high circulating and tissue levels of iron, expression of hepcidin increases. This also occurs when there is an on-going inflammatory process or infection resulting in a reduced iron supply and a functional ID/IDA. Conversely the transcription of hepcidin is inhibited in ID, tissue hypoxia and increased erythropoiesis with the aim of facilitating absorption of iron in the gut and release of iron from tissue stores.

• 30.
  

  a) T b) T c) T d) T e) T

Hepcidin is crucial for regulating both gut iron absorption and erythrocyte recycling. If iron has been taken up by enterocytes but is not required, hepcidin prevents entry of iron into the circulation by reducing the expression of ferroportin, a transmembrane protein that transports iron from the inside to the outside of a cell. Iron therefore remains in the enterocyte and is lost when these cells are sloughed off. Similarly, if recycled iron contained within macrophages is not needed, hepcidin reduces the expression of ferroportin and iron again does not re-enter the circulation. If there is acute blood loss, hepcidin production decreases which increases importation of iron by ferroportin. In ID, hepatic production of transferrin and expression of transferrin receptors by the bone marrow and other tissues increases. Some of the iron from erythrocyte breakdown remains in macrophages as ferritin or as the water soluble form of iron, hemosiderin. Levels of hepcidin are low in pre-menopausal, menstruating women and return to approximate parity with men in the post-menopausal period.