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| Specific treatment for menorrhagia is based on a number of factors, including: |
 Patient's age |
| Patient's overall health and medical history |
| The extent of the condition |
| The cause of the condition |
| Tolerance for specific medications, procedures or therapies |
| Effects of the condition on the patient's lifestyle |
| Patient's opinion or personal preference |
Therapeutic options for the control of menorrhagia in women with underlying bleeding disorders include medical treatments and surgical treatments. |
| They are similar to the treatment options for menorrhagia in general with the exception of DDAVP and clotting factor replacement. |
| However, management of women with inherited bleeding disorders requires additional monitoring of the haemostatic parameters and awareness of the increased risk of bleeding with any surgical interventions. |
| Medical treatment of menorrhagia |
| Antifibrinolytics . An increased uterine fibrinolytic activity, most likely due to high levels of endometrium-derived plasmin and plasminogen activators [57-58], is found in women with menorrhagia. |
| Tranexamic acid is an antifibrinolytic agent that reversibly blocks lysine-binding sites on plasminogen and prevents fibrin degradation [59]. |
| The recommended oral dose of tranexamic acid for the treatment of menorrhagia is 1 g three to four times daily for 3-4 days (maximum total daily dose of 4 g), starting from the onset of menstruation [70]. These doses may reduce menstrual blood loss by 34-59% over 2-3 cycles [60-64] |
Oral tranexamic acid is generally well tolerated [65]. Epidemiological population studies have not indicated that antifibrinolytic use is associated with thromboembolic events [66-69], but cases have been reported. |
| Combined oral contraceptives (COCs ). COCs, a highly reliable method of birth control, are also useful for cycle regulation and reduction in the incidence of dysmenorrhea and premenstrual tension. |
| COCs are reported to be effective [3] in reducing menstrual blood loss in women with bleeding disorders, but the response is variable and unpredictable [71] and there are no studies confirming their efficacy using objective measures of clinical response [72]. |
| The extended or continuous administration of COC (>28 days of active pills) has been reported as a successful regime in the treatment of endometriosis, dysmenorrhea, and other menstruation-association symptoms [73-76]. |
| Increased risk of thrombosis is the main concern associated with the use of COCs. However, women with bleeding disorders have a low inherited thrombotic risk. Serious side effects of COC are uncommon, but include hypertension and, very rarely, impaired liver function and hepatic tumours [22]. Other less serious side effects include nausea, vomiting, headache, breast tenderness, breakthrough bleeding, fluid retention, depression and skin reactions. |
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| Desmopressin. (1-desamino-8-d-arginine vasopression, DDAVP) is a synthetic analogue of the antidiuretic hormone vasopressin. It increases plasma concentration of FVIII and VWF through endogenous release [78-80]. Desmopressin can be administered parenterally via intravenous or subcutaneous injection, or nasally as a spray. |
| The optimal haemostatic effect of DDAVP is achieved with a dosage of 0.3 µg/kg, which increases plasma FVIII and VWF levels 2-6 fold after intravenous or subcutaneous administration [81-82]. |
| Intranasal administration of DDAVP is an attractive route because it allows patients to treat themselves at home without delay in the event of bleeding episodes, e.g. at the onset of menstruation, and without the use of needles [83-84]. The effect of intranasal administration of 300 µg with a metered-dose spray is comparable with that of 0.2 µg/kg intravenous injection [78-85]. |
| There are a few side effects related to its vasomotor effects as mild tachycardia, headache and flushing. Due to the antidiuretic effect of DDAVP, there is a small risk of hyponatraemia and potentially of water intoxication. |
| Progestins . Progestin on days 5-26 effectively reduces menstrual blood loss, but due to its adverse effects, it is suitable only for short-term therapy [90]. |
Oral progestins in high doses alone, or in combination with DDAVP or clotting factor concentrate, may be useful in the treatment of acute menorrhagia in women with inherited bleeding disorders. They should only be used in the short-term, since long-term therapy reduces bone mineral density and increases the risk of osteoporosis [3]. |
Nonsteroidal anti-inflammatory drugs (NSAIDs) . NSAIDs (e.g. mefenamic acid and naproxen) have been shown to be more effective than placebo in reducing menstrual blood loss but less effective than either tranexamic acid or danazol [91]. NSAIDs have the advantage of reducing menstrual pain and menstrual migraine. However, their use is contraindicated in women with inherited bleeding disorders due to their anti-aggregatory effect on platelet function |
Ethamsylate. Ethamsylate is a haemostatic agent that maintains platelet and capillary integrity and affects prostaglandin synthesis. There are no data on the efficacy of this treatment in women with bleeding disorders, but in view of its mode of action, it may have a different effect on heavy menstrual loss in these women, which warrants further studies [22]. |
| Gonadotrophin-releasing hormone (GnRH). GnRH agonists induce amenorrhoea [92-94], but data on their effectiveness in the treatment of menorrhagia related to bleeding disorders are lacking. Due to their numerous adverse effects, they are not recommended for long-term treatment of menorrhagia. GnRH agonists can be used if surgery is soon or for other temporary reasons (e.g. when traveling). |
| Levonorgestrel-releasing intrauterine system (LNG-IUS). The LNG-IUS releases 20 mg of LNG every 24 h over a recommended duration of use of 5 years. It suppresses endometrial growth causing the glands of the endometrium to become atrophic and the epithelium inactive [95]. |
| It reduces menstrual blood loss significantly (by 74-97%) and improves quality of life considerably [95] The effectiveness of the treatment is comparable with the results of endometrial ablation and hysterectomy, and patient satisfaction is similar [96-98]. Additional benefits may include alleviation of menstrual pain [98-100] and premenstrual symptoms [97]. |
| Insertion of the IUS is associated with a small risk of uterine perforation and infection [101-102] |
| The commonest side effect is irregular bleeding or spotting in the first 3-6 months after insertion [96]. Hormonal adverse effects (breast tenderness, bloating, nausea) are slightly more common during the first year than they are if endometrial resection or thermal balloon is used [97-98]. |
| IUS reduces anxiety and depressed mood and has probably no effect on sexual function [103 , 104]. |
| The use of LNG-IUS in women with inherited bleeding disorders has been evaluated in 16 women with menorrhagia not responding to medical treatment, all with mild to moderate bleeding disorders and the outcome was very good [105]. However, further studies are required to evaluate the effectiveness of LNG-IUS in women with severe factor deficiencies. Women with bleeding disorders could potentially be at risk of bleeding at the time of insertion. Adequate haemostatic coverage is recommended especially in women with severe forms of bleeding disorders. |
Clotting factor. Clotting factor replacement, with either recombinant or plasma-derived factor concentrate, will be required in some women with bleeding disorders, especially in adolescents [106], those with severe deficiency and when they present acutely. The role of clotting factors replacement as prophylaxis in severe bleeders need to be analysed. |
| Surgical treatment for menorrhagia |
| Surgical interventions treatment of menorrhagia are commonly performed and may be required in some women who do not tolerate medical treatments or where such treatments have failed. |
Women with inherited bleeding disorders are at a greater risk of bleeding complications from surgery, including increased perioperative and delayed (7-10 days after surgery) bleeding. Appropriate preoperative coagulation screening and adequate haemostatic coverage during any gynaecological procedure is crucial to minimize the risk of haemorrhagic complications. |
| Hysterectomy . Hysterectomy is an established, effective and definitive treatment for menorrhagia associated with high patient satisfaction [3-22]. However, hysterectomy is a major surgical procedure with significant physical and emotional complications and social and economic costs. Hysterectomy also has a risk of long-term complications, including the possibility of early ovarian failure, and urinary and sexual problems. For these reasons, less invasive alternatives (e.g. endometrial resection and ablation) have been developed for the treatment of menorrhagia. |
| Endometrial ablation. Endometrial ablative techniques, which destroy the lining of the uterus, are increasingly used today as an effective alternative to hysterectomy for the management of heavy menstrual bleeding. They have a shorter operating time and hospital stay, quicker recovery and fewer postoperative complications than hysterectomy [107]. A disadvantage of endometrial ablation is that the results may not be permanent in one third to one half of women who undergo the procedure. |
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