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1. Definition of menorrhagia Menorrhagia is the medical term for menstrual periods with abnormally heavy or prolonged bleeding. HMB is defined as a blood loss of greater than 80 mL per period. In reality, methods to quantify menstrual blood loss are both inaccurate (poor correlation with haemoglobin level) and impractical and so a clinical diagnosis based on the patient’s own perception of blood loss is preferred. 2. What is the normal menstrual flow and menstrual cycle
3. Possible causes of menorrhagia Aetiology • Fibroids (Figure 5.1) • Endometrial polyps (Figure 5.2) • Coagulation disorders, e.g. von Willebrand’s disease • Pelvic inflammatory disease (PID) • Thyroid disease • Drug therapy (e.g. warfarin) • Intrauterine contraceptive devices (IUCDs) • Endometrial/cervical carcinoma. Despite appropriate investigations, often no pathology can be identified. Bleeding of endometrial origin (BEO) is the diagnosis of exclusion. This replaces the older ‘dysfunctional uterine bleeding’ (DUB). Disordered endometrial prostaglandin production has been implicated in the aetiology of BEO, as have abnormalities of endometrial vascular development. 4. Relevant menstrual history and what are the abnormal findings 5. Significance of other Hx
6. Relate abnormal findings with sign and symptoms
(gyaneo by ten teachers)
7. Relevant lab investigation 8. Interpret the lab findings Full blood count A full blood count (FBC) should be carried out in all women with HMB to ascertain the need for iron therapy (and in certain cases, blood transfusion). Coagulation screen Referral for a haematological opinion should be considered in women with a history consistent with a coagulation disorder (see Table 5.1). Pelvic ultrasound scan A pelvic ultrasound scan (USS) should be performed: • when a pelvic mass is palpated on examination (suggestive of fibroids); • when symptoms suggest an endometrial polyp, e.g. irregular or intermenstrual bleeding; • when drug therapy for HMB is unsuccessful. High vaginal and endocervical swabs • High vaginal and endocervical swabs should be taken: • when unusual vaginal discharge is reported or observed on examination; • where there are risk factors for PID. Endometrial biopsy Biopsy should be performed: • in those aged >45 years; • if irregular or intermenstrual bleeding; • drug therapy has failed. A Pipelle™ endometrial biopsy can be performed in the outpatient setting. It is performed as follows: • a speculum examination is carried out and the cervix is completely visualized; • a vulsellum instrument may be required to grasp the cervix and provide gentle traction, thereby straightening the endocervical canal; • the Pipelle sampler (Figure 5.3) is carefully inserted through the cervical os until it reaches the fundus of the uterus. The length of the uterus is noted; • the inner part of the Pipelle is withdrawn to create a vacuum and the device is gently moved in and out to obtain a sample of endometrial tissue; • the Pipelle is removed and the tissue is expelled into a histopathology container of formalin. An outpatient hysteroscopy (Figure 5.4) with endometrial biopsy may be indicated if: • Pipelle biopsy attempt fails; • Pipelle biopsy sample is insufficient for histopathology assessment; • there is an abnormality on USS, e.g. suggested endometrial polyp or submucosal fibroid; • patient is known to poorly tolerate speculum examinations (more comfortable vaginoscopic approach can be used). If the patient fails to tolerate an outpatient procedure or the cervix needs to be dilated to enter the cavity, then a hysteroscopy and endometrial biopsy under general anaesthetic may be required. Thyroid function tests. This should only be carried out when the history is suggestive of a thyroid disorder.
9. Normal histology of endometrium 10. Normal structure of uterus and ovary 11. What is pap smear A Pap test is a test of a sample of cells taken from a woman's cervix or vagina. The test is used to look for changes in the cells of the cervix and vagina that show cancer or conditions that may develop into cancer. It is the best tool to detect precancerous conditions and hidden, small tumors that may lead to cervical cancer. If detected early, cervical cancer can be cured. The Pap test is done during a pelvic exam. A doctor uses a device called a speculum to widen the opening of the vagina so that the cervix and vagina can be examined. A plastic spatula and small brush are used to collect cells from the cervix. After the cells are taken, they are placed into a solution. The solution is sent to a lab for testing. 12. Complication of menorrhagia Excessive or prolonged menstrual bleeding can lead to other medical conditions, including:
Iron deficiency anemia. In this common type of anemia, your blood is low in hemoglobin, a substance that enables red blood cells to carry oxygen to tissues. Low hemoglobin may be the result of insufficient iron. Menorrhagia may decrease iron levels enough to increase the risk of iron deficiency anemia. Signs and symptoms include pale skin, weakness and fatigue. Although diet plays a role in iron deficiency anemia, the problem is complicated by heavy menstrual periods. Most cases of anemia are mild, but even mild anemia can cause weakness and fatigue. Moderate to severe anemia can also cause shortness of breath, rapid heart rate, lightheadedness and headaches.
Severe pain. Along with heavy menstrual bleeding, you might have painful menstrual cramps (dysmenorrhea). Sometimes the cramps associated with menorrhagia are severe enough to require prescription medication or a surgical procedure.
13. What is DUB Dysfunctional uterine bleeding (DUB) is irregular uterine bleeding that occurs in the absence of recognizable pelvic pathology, general medical disease, or pregnancy. It reflects a disruption in the normal cyclic pattern of ovulatory hormonal stimulation to the endometrial lining. The bleeding is unpredictable in many ways. It may be excessively heavy or light and may be prolonged, frequent, or random.
14. Pathophysiology of DUB Patients with dysfunctional uterine bleeding (DUB) have lost cyclic endometrial stimulation that arises from the ovulatory cycle. As a result, these patients have constant, noncycling estrogen levels that stimulate endometrial growth. Proliferation without periodic shedding causes the endometrium to outgrow its blood supply. The tissue breaks down and sloughs from the uterus. Subsequent healing of the endometrium is irregular and dyssynchronous. Chronic stimulation by low levels of estrogen will result in infrequent, light DUB. Chronic stimulation from higher levels of estrogen will lead to episodes of frequent, heavy bleeding.
15. Management of DUB MANAGEMENT Medical Treatment Non Steroidal Anti-Inflammatory Drugs Endometrial prostaglandins are elevated with excessive menstruation, and he non- steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels through the inhibition of the cyclo-oxygenase enzyme with reductions in menstrual blood loss of 25-35% (Irvine &, Cameron, 1999; level 9). NSAIDs are found to be less effective than tranexamic acid or danazol, but as effective as other medical treatments (Lethaby, Irvine & Cameron, 2003; level 1), with the added advantage of relieving dysmenorrhoea (Fraser et al,1981; level 3) Progestogens Progestogens administered from the fifteen th day or from 19th - 26th day of the menstrual cycle were significantly less effective in reducing menstrual blood loss when compared to other medical therapies (Lethaby, Irvine & Cameron, 2003; level 1), and found to be one of the least effective agents (Roy & Bhattacharya, 2004; level 5). However, progestogen therapy administered for 21 days of the menstrual cycle results in a significant reduction in menstrual blood loss, (Lethaby, 2003b; level 1), although they have been found to be ineffective unless taken at high doses (Irvine & Cameron, 1999; level 9). Combined oral contraceptive pills The combined oral contraceptive pill (OCP) in addition to providing contraception causes a 50% reduction in menstrual blood loss by regular shedding of a thinner endometrium and by inhibiting ovulation (Irvine & Cameron, 1999, level 9). Danazol Danazol is a synthetic steroid that suppresses oestrogen and progesterone receptors in the endometrium, leading to endometrial atrophy (thinning of the lining of the uterus) and reduced menstrual loss. It is an effective treatment for heavy menstrual bleeding. However, its side-effect profile, its lack of acceptability to women and the need for continuing treatment limits its use (Roy & Bhattacharya, 2004; level 5; Beaumont et al, 2003; level 1).
Anti-fibrinolytic agents Tranexamic acid, a synthetic derivative of the amino acid lysine, exerts an antifibrinolytic effect through reversibleblockade on plasminogen, producing a 50% reduction in menstrual loss (Irvine & Cameron, 1999; level 9). Anti-fibrinolytic therapy causes a greater reduction in objective measurements of heavy menstrual bleeding compared to placebo or other medical therapies (Lethaby, Farquhar & Cooke 2003; level 1Bonnar & Sheppard, 1996, level 1),and is not associated with an increase in side effects (Lethaby, Farquhar & Cooke, 2003; level 1, Lindoff, Rybo & Astedt, 1997; level 5). Levonorgestrel intrauterine system The levonorgestrel intrauterine system (LNG IUS) is a T shaped intrauterine device releasing a steady amount of levonorgestrel (20 μg /24 hours) from a steroid reservoir around the vertical stem of the device. It reduces menstrual blood loss by 80% (Irvine & Cameron, 1999; Level 9), and is found to be more effective than cyclical norethisterone, with patients being more satisfied and willing to continue with treatment. However, these patients experience more side effects such as inter-menstrual bleeding and breast tenderness (Lethaby, 2003; level 1). Compared to transcervical resection of the endometrium (TCRE), the LNG IUS produces smaller mean reduction in menstrual blood loss, but there is no difference in the rate of satisfaction with treatment. LNG-IUS appears equally beneficial in improving quality of life and may control bleeding as effectively as conservative surgery over the long term (Marjori banks, Lethaby, & Farquhar, 2003; level 1). GnRH agonists Gonadatrophin-releasing hormone (GnRH) agonists induce a reversible hypoestrogenic state, reducing total uterine volume. They are highly effective, but their sideeffects make them suitable only for short-term use (Irvine & Cameron, 1999, level 9).GnRH agonists may obviate emergency surgery in patients with high surgical risk (Vercellini, 1992; level 3).
Surgical Management Medical versus surgical treatment Medical treatment for menorrhagia is not as effective as surgery despite improvement in control of bleeding. Oral medical therapy is associated with higher incidence of side effects, and approximately 60% of women who had medical treatment would require surgery by 2 years. Surgery has been found to reduce menstrual bleeding more than medical treatment at one year, although the majority of women prefer medical treatment (Marjoribanks, Lethaby & Farquhar, 2003; level 1). Dilatation and curettage There is little evidence on the effectiveness of dilatation and curettage (D&C) for the relief of menorrhagia.It is not cost effective for the diagnosis of endometrial malignancy in women under 40 years since the prevalence of serious uterine conditions and endometrial cancer is low (Coulter et al,1993; level 9). The potential benefits need to be weighed against the risks of anaesthesia and possible complications like uterine perforation and laceration of the cervix (MacKenzie & Bibby,1978; level 9).Moreover, a significant proportion of endometrial lesions are not detected by D&C, (Vessey, Clarke, & MacKenzie, 1979) and its usefulness as a diagnostic tool has been repeatedly questioned. D&C may have a diagnostic role when endometrial biopsy is inconclusive and the symptoms persist or when the underlying pathology is suspect. Endometrial destruction Endometrial destruction procedures are less invasive, more convenient and less expensive when no other gynecological condition is involved. It enables women to avoid major surgery and results in shorter hospital stay and convalescence. The various energy sources used to destroy the endometrium, are all comparable in terms of efficacy, and the re-operation rate ranges from 0 to 38.2%. The rate is higher in women under the age 35 years in studies where they have been observed for longer duration. The first-generation techniques involve lower costs than a hysterectomy, but the second-generation endometrial destruction techniques involve relatively high purchase and disposable supplies costs. However, these new techniques take less time to perform and have a lower incidence of intra-operative complications. The clinical impact of these two benefits has yet to be demonstrated (AETMIS, 2002; level 1). Hysterectomy Hysterectomy is the most widely used treatment, and can be performed abdominally, vaginally or laparoscopically. The vaginal and laparoscopic approaches cause fewer complications and provide a shorter hospital stay and convalescence than abdominal hysterectomy. Although with hysterectomy there is a permanent cessation of menstrual flow resulting in a high level of satisfaction, it is a major invasive procedure incurring morbidity, mortality and costs with a risk oflate complications as well. (AETMIS, 2002; level 1). Laparoscopic assisted vaginal hysterectomy is associated with longer operating times, and higher operating costs, but total costs are lower than abdominal hysterectomy.
3. Possible causes of menorrhagia Aetiology • Fibroids (Figure 5.1) • Endometrial polyps (Figure 5.2) • Coagulation disorders, e.g. von Willebrand’s disease • Pelvic inflammatory disease (PID) • Thyroid disease • Drug therapy (e.g. warfarin) • Intrauterine contraceptive devices (IUCDs) • Endometrial/cervical carcinoma. Despite appropriate investigations, often no pathology can be identified. Bleeding of endometrial origin (BEO) is the diagnosis of exclusion. This replaces the older ‘dysfunctional uterine bleeding’ (DUB). Disordered endometrial prostaglandin production has been implicated in the aetiology of BEO, as have abnormalities of endometrial vascular development. 4. Relevant menstrual history and what are the abnormal findings 5. Significance of other Hx
6. Relate abnormal findings with sign and symptoms
(gyaneo by ten teachers)
7. Relevant lab investigation 8. Interpret the lab findings Full blood count A full blood count (FBC) should be carried out in all women with HMB to ascertain the need for iron therapy (and in certain cases, blood transfusion). Coagulation screen Referral for a haematological opinion should be considered in women with a history consistent with a coagulation disorder (see Table 5.1). Pelvic ultrasound scan A pelvic ultrasound scan (USS) should be performed: • when a pelvic mass is palpated on examination (suggestive of fibroids); • when symptoms suggest an endometrial polyp, e.g. irregular or intermenstrual bleeding; • when drug therapy for HMB is unsuccessful. High vaginal and endocervical swabs • High vaginal and endocervical swabs should be taken: • when unusual vaginal discharge is reported or observed on examination; • where there are risk factors for PID. Endometrial biopsy Biopsy should be performed: • in those aged >45 years; • if irregular or intermenstrual bleeding; • drug therapy has failed. A Pipelle™ endometrial biopsy can be performed in the outpatient setting. It is performed as follows: • a speculum examination is carried out and the cervix is completely visualized; • a vulsellum instrument may be required to grasp the cervix and provide gentle traction, thereby straightening the endocervical canal; • the Pipelle sampler (Figure 5.3) is carefully inserted through the cervical os until it reaches the fundus of the uterus. The length of the uterus is noted; • the inner part of the Pipelle is withdrawn to create a vacuum and the device is gently moved in and out to obtain a sample of endometrial tissue; • the Pipelle is removed and the tissue is expelled into a histopathology container of formalin. An outpatient hysteroscopy (Figure 5.4) with endometrial biopsy may be indicated if: • Pipelle biopsy attempt fails; • Pipelle biopsy sample is insufficient for histopathology assessment; • there is an abnormality on USS, e.g. suggested endometrial polyp or submucosal fibroid; • patient is known to poorly tolerate speculum examinations (more comfortable vaginoscopic approach can be used). If the patient fails to tolerate an outpatient procedure or the cervix needs to be dilated to enter the cavity, then a hysteroscopy and endometrial biopsy under general anaesthetic may be required. Thyroid function tests. This should only be carried out when the history is suggestive of a thyroid disorder.
9. Normal histology of endometrium 10. Normal structure of uterus and ovary 11. What is pap smear A Pap test is a test of a sample of cells taken from a woman's cervix or vagina. The test is used to look for changes in the cells of the cervix and vagina that show cancer or conditions that may develop into cancer. It is the best tool to detect precancerous conditions and hidden, small tumors that may lead to cervical cancer. If detected early, cervical cancer can be cured. The Pap test is done during a pelvic exam. A doctor uses a device called a speculum to widen the opening of the vagina so that the cervix and vagina can be examined. A plastic spatula and small brush are used to collect cells from the cervix. After the cells are taken, they are placed into a solution. The solution is sent to a lab for testing. 12. Complication of menorrhagia Excessive or prolonged menstrual bleeding can lead to other medical conditions, including:
Iron deficiency anemia. In this common type of anemia, your blood is low in hemoglobin, a substance that enables red blood cells to carry oxygen to tissues. Low hemoglobin may be the result of insufficient iron. Menorrhagia may decrease iron levels enough to increase the risk of iron deficiency anemia. Signs and symptoms include pale skin, weakness and fatigue. Although diet plays a role in iron deficiency anemia, the problem is complicated by heavy menstrual periods. Most cases of anemia are mild, but even mild anemia can cause weakness and fatigue. Moderate to severe anemia can also cause shortness of breath, rapid heart rate, lightheadedness and headaches.
Severe pain. Along with heavy menstrual bleeding, you might have painful menstrual cramps (dysmenorrhea). Sometimes the cramps associated with menorrhagia are severe enough to require prescription medication or a surgical procedure.
13. What is DUB Dysfunctional uterine bleeding (DUB) is irregular uterine bleeding that occurs in the absence of recognizable pelvic pathology, general medical disease, or pregnancy. It reflects a disruption in the normal cyclic pattern of ovulatory hormonal stimulation to the endometrial lining. The bleeding is unpredictable in many ways. It may be excessively heavy or light and may be prolonged, frequent, or random.
14. Pathophysiology of DUB Patients with dysfunctional uterine bleeding (DUB) have lost cyclic endometrial stimulation that arises from the ovulatory cycle. As a result, these patients have constant, noncycling estrogen levels that stimulate endometrial growth. Proliferation without periodic shedding causes the endometrium to outgrow its blood supply. The tissue breaks down and sloughs from the uterus. Subsequent healing of the endometrium is irregular and dyssynchronous. Chronic stimulation by low levels of estrogen will result in infrequent, light DUB. Chronic stimulation from higher levels of estrogen will lead to episodes of frequent, heavy bleeding.
15. Management of DUB MANAGEMENT Medical Treatment Non Steroidal Anti-Inflammatory Drugs Endometrial prostaglandins are elevated with excessive menstruation, and he non- steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels through the inhibition of the cyclo-oxygenase enzyme with reductions in menstrual blood loss of 25-35% (Irvine &, Cameron, 1999; level 9). NSAIDs are found to be less effective than tranexamic acid or danazol, but as effective as other medical treatments (Lethaby, Irvine & Cameron, 2003; level 1), with the added advantage of relieving dysmenorrhoea (Fraser et al,1981; level 3) Progestogens Progestogens administered from the fifteen th day or from 19th - 26th day of the menstrual cycle were significantly less effective in reducing menstrual blood loss when compared to other medical therapies (Lethaby, Irvine & Cameron, 2003; level 1), and found to be one of the least effective agents (Roy & Bhattacharya, 2004; level 5). However, progestogen therapy administered for 21 days of the menstrual cycle results in a significant reduction in menstrual blood loss, (Lethaby, 2003b; level 1), although they have been found to be ineffective unless taken at high doses (Irvine & Cameron, 1999; level 9). Combined oral contraceptive pills The combined oral contraceptive pill (OCP) in addition to providing contraception causes a 50% reduction in menstrual blood loss by regular shedding of a thinner endometrium and by inhibiting ovulation (Irvine & Cameron, 1999, level 9). Danazol Danazol is a synthetic steroid that suppresses oestrogen and progesterone receptors in the endometrium, leading to endometrial atrophy (thinning of the lining of the uterus) and reduced menstrual loss. It is an effective treatment for heavy menstrual bleeding. However, its side-effect profile, its lack of acceptability to women and the need for continuing treatment limits its use (Roy & Bhattacharya, 2004; level 5; Beaumont et al, 2003; level 1).
Anti-fibrinolytic agents Tranexamic acid, a synthetic derivative of the amino acid lysine, exerts an antifibrinolytic effect through reversibleblockade on plasminogen, producing a 50% reduction in menstrual loss (Irvine & Cameron, 1999; level 9). Anti-fibrinolytic therapy causes a greater reduction in objective measurements of heavy menstrual bleeding compared to placebo or other medical therapies (Lethaby, Farquhar & Cooke 2003; level 1Bonnar & Sheppard, 1996, level 1),and is not associated with an increase in side effects (Lethaby, Farquhar & Cooke, 2003; level 1, Lindoff, Rybo & Astedt, 1997; level 5). Levonorgestrel intrauterine system The levonorgestrel intrauterine system (LNG IUS) is a T shaped intrauterine device releasing a steady amount of levonorgestrel (20 μg /24 hours) from a steroid reservoir around the vertical stem of the device. It reduces menstrual blood loss by 80% (Irvine & Cameron, 1999; Level 9), and is found to be more effective than cyclical norethisterone, with patients being more satisfied and willing to continue with treatment. However, these patients experience more side effects such as inter-menstrual bleeding and breast tenderness (Lethaby, 2003; level 1). Compared to transcervical resection of the endometrium (TCRE), the LNG IUS produces smaller mean reduction in menstrual blood loss, but there is no difference in the rate of satisfaction with treatment. LNG-IUS appears equally beneficial in improving quality of life and may control bleeding as effectively as conservative surgery over the long term (Marjori banks, Lethaby, & Farquhar, 2003; level 1). GnRH agonists Gonadatrophin-releasing hormone (GnRH) agonists induce a reversible hypoestrogenic state, reducing total uterine volume. They are highly effective, but their sideeffects make them suitable only for short-term use (Irvine & Cameron, 1999, level 9).GnRH agonists may obviate emergency surgery in patients with high surgical risk (Vercellini, 1992; level 3).
Surgical Management Medical versus surgical treatment Medical treatment for menorrhagia is not as effective as surgery despite improvement in control of bleeding. Oral medical therapy is associated with higher incidence of side effects, and approximately 60% of women who had medical treatment would require surgery by 2 years. Surgery has been found to reduce menstrual bleeding more than medical treatment at one year, although the majority of women prefer medical treatment (Marjoribanks, Lethaby & Farquhar, 2003; level 1). Dilatation and curettage There is little evidence on the effectiveness of dilatation and curettage (D&C) for the relief of menorrhagia.It is not cost effective for the diagnosis of endometrial malignancy in women under 40 years since the prevalence of serious uterine conditions and endometrial cancer is low (Coulter et al,1993; level 9). The potential benefits need to be weighed against the risks of anaesthesia and possible complications like uterine perforation and laceration of the cervix (MacKenzie & Bibby,1978; level 9).Moreover, a significant proportion of endometrial lesions are not detected by D&C, (Vessey, Clarke, & MacKenzie, 1979) and its usefulness as a diagnostic tool has been repeatedly questioned. D&C may have a diagnostic role when endometrial biopsy is inconclusive and the symptoms persist or when the underlying pathology is suspect. Endometrial destruction Endometrial destruction procedures are less invasive, more convenient and less expensive when no other gynecological condition is involved. It enables women to avoid major surgery and results in shorter hospital stay and convalescence. The various energy sources used to destroy the endometrium, are all comparable in terms of efficacy, and the re-operation rate ranges from 0 to 38.2%. The rate is higher in women under the age 35 years in studies where they have been observed for longer duration. The first-generation techniques involve lower costs than a hysterectomy, but the second-generation endometrial destruction techniques involve relatively high purchase and disposable supplies costs. However, these new techniques take less time to perform and have a lower incidence of intra-operative complications. The clinical impact of these two benefits has yet to be demonstrated (AETMIS, 2002; level 1). Hysterectomy Hysterectomy is the most widely used treatment, and can be performed abdominally, vaginally or laparoscopically. The vaginal and laparoscopic approaches cause fewer complications and provide a shorter hospital stay and convalescence than abdominal hysterectomy. Although with hysterectomy there is a permanent cessation of menstrual flow resulting in a high level of satisfaction, it is a major invasive procedure incurring morbidity, mortality and costs with a risk oflate complications as well. (AETMIS, 2002; level 1). Laparoscopic assisted vaginal hysterectomy is associated with longer operating times, and higher operating costs, but total costs are lower than abdominal hysterectomy.
