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Where an underlying cause can be identified, treatment may be directed at this. Clearly heavy periods at menarche and menopause may settle spontaneously (the menarche being the start and menopause being the cessation of periods).
If the degree of bleeding is mild, all that may be sought by the woman is the reassurance that there is no sinister underlying cause. If anemia occurs due to bleeding then iron tablets may be used to help restore normal hemoglobin levels.
The condition is often treated with hormones, particularly as abnormal uterine bleeding commonly occurs in the early and late menstrual years when contraception is also sought. Usually, oral combined contraceptive or progesterone only pills may be taken for a few months, but for longer-term treatment the alternatives of injected Depo Provera or the more recent progesterone releasing IntraUterine System (IUS) may be used. Fibroids may respond to hormonal treatment, and if they do not, then surgical removal may be required.
Tranexamic acid tablets that may also reduce loss by up to 50%. This may be combined with hormonal medication previously mentioned.
Anti-inflammatory medication like NSAIDs may also be used. NSAIDs are the first-line medications in ovulatory menorrhagia, resulting in an average reduction of 20-46% in menstrual blood flow. For this purpose, NSAIDs are ingested for only 5 days of the menstrual cycle, limiting their most common adverse effect of dyspepsia.
A definitive treatment for menorrhagia is to perform hysterectomy (removal of the uterus). The risks of the procedure have been reduced with measures to reduce the risk of deep vein thrombosis after surgery, and the switch from the front abdominal to vaginal approach greatly minimizing the discomfort and recuperation time for the patient; however extensive fibroids may make the womb too large for removal by the vaginal approach. Small fibroids may be dealt with by local removal (myomectomy). A further surgical technique is endometrial ablation (destruction) by the use of applied heat (thermoablation).
In the UK the use of hysterectomy for menorrhagia has been almost halved between 1989 and 2003. This has a number of causes: better medical management, endometrial ablation and particularly the introduction of IUS which may be inserted in the community and avoid the need for specialist referral; in one study up to 64% of women cancelled surgery.
These have been ranked by the UK's National Institute for Health and Clinical Excellence:
- First line
- Intrauterine device with progesterone
- Second Line
- Tranexamic acid an antifibrinolytic agent
- Nonsteroidal anti-inflammatory drugs (NSAIDs).
- Combined oral contraceptive pills to prevent proliferation of the endometrium
- Third line
- Oral progestogen (e.g. norethisterone), to prevent proliferation of the endometrium
- Injected progestogen (e.g. Depo provera)
- Other options
- Gonadotropin-releasing hormone agonist
Drug of choice is progesterone.
Management of dysfunctional uterine bleeding predominantly consists of reassurance, though mid-cycle estrogen and late-cycle progestin can be used for mid- and late-cycle bleeding respectively.
Also, non-specific hormonal therapy such as combined high-dose estrogen and high-dose progestin can be given. Ormeloxifene is a non-hormonal medication that treats DUB but is only legally available in India.
The goal of therapy should be to arrest bleeding, replace lost iron to avoid anemia, and prevent future bleeding.
Excessive movement before any treatments or surgeries will cause excessive bleeding.
A hysterectomy may be performed in some cases.
Treatment depends on the cause. In cases where malignancy is ruled out, hormone supplementation or the therapeutic use of hormonal contraception is usually recommended to induce bleeding on a regular schedule. Selective progesterone receptor modulators (SPRMs) are sometimes used to stop uterine bleeding.
A menstrual disorder is an abnormal condition in a woman's menstrual cycle.
Excessive menstruation between puberty and 19 years of age is called puberty menorrhagia. Excessive menstruation is defined as bleeding over 80 ml per menstrual period or lasting more than 7 days. The most common cause for puberty menorrhagia is dysfunctional uterine bleeding. The other reasons are idiopathic thrombocytopenic purpura, hypothyroidism, genital tuberculosis, polycystic ovarian disease, leukemia and coagulation disorders. The most common physiological reason for puberty menorrhagia is the immaturity of hypothalamic-pituitary-ovarian axis, leading to inadequate positive feedback and sustained high estrogen levels. Most patients present with anemia due to excessive blood loss.
The patient is assessed with a thorough medical history, physical examination (to look for features of anemia), gynaecological examination (to rule out local causes) and laboratory investigations (to rule out coagulopathies and malignancy). It is mandatory to exclude pregnancy. The treatment is determined based on the cause of menorrhagia. In case of puberty menorrhagia due to immaturity of hypothalamic axis, hormonal therapy is beneficial. Treatment for blood loss should be done simultaneously with iron therapy in mild to moderate blood loss and blood transfusion in severe blood loss.
Dysmenorrhea (or dysmenorrhoea), cramps or painful menstruation, involves menstrual periods that are accompanied by either sharp, intermittent pain or dull, aching pain, usually in the pelvis or lower abdomen.
Severe acute bleeding, such as caused by ectopic pregnancy and post-partum hemorrhage, leads to hypovolemia (the depletion of blood from the circulation), progressing to shock. This is a medical emergency and requires hospital attendance and intravenous fluids, usually followed by blood transfusion. Once the circulating volume has been restored, investigations are performed to identify the source of bleeding and address it. Uncontrolled life-threatening bleeding may require uterine artery embolization (occlusion of the blood vessels supplying the uterus), laparotomy (surgical opening of the abdomen), occasionally leading to hysterectomy (removal of the uterus) as a last resort.
A possible complication from protracted vaginal blood loss is iron deficiency anemia, which can develop insidiously. Eliminating the cause will resolve the anemia, although some women require iron supplements or blood transfusions to improve the anemia.
10% of cases occur in women who are ovulating, but progesterone secretion is prolonged because estrogen levels are low. This causes irregular shedding of the uterine lining and break-through bleeding. Some evidence has associated Ovulatory DUB with more fragile blood vessels in the uterus.
It may represent a possible endocrine dysfunction, resulting in menorrhagia or metrorrhagia.
Mid-cycle bleeding may indicate a transient estrogen decline, while late-cycle bleeding may indicate progesterone deficiency.
Menometrorrhagia is a condition in which prolonged or excessive uterine bleeding occurs irregularly and more frequently than normal. It is thus a combination of metrorrhagia and menorrhagia.
In 2011, the International Federation of Gynaecology and Obstetrics (FIGO) recognized two systems designed to aid research, education, and clinical care of women with abnormal uterine bleeding (AUB) in the reproductive years.
Adenomyosis itself can cause infertility issues, however, fertility can be improved if the adenomyosis has resolved following hormone therapies like levonorgestrel therapy. The discontinuation of medication or removal of IUD can be timed to be coordinated with fertility treatments. There has also been one report of a successful pregnancy and healthy birth following high-frequency ultrasound ablation of adenomyosis.
Preterm labour and premature rupture of membranes both occur more frequently in women with adenomyosis.
In sub-fertile women who received in-vitro fertilization (IVF), women with adenomyosis were less likely to become pregnant and subsequently more likely to experience a miscarriage. Given this, it is encouraged to screen women for adenomyosis by TVUS or MRI before starting assisted reproduction treatments (ART).
Adenomyosis can only be cured definitively with surgical removal of the uterus. As adenomyosis is responsive to reproductive hormones, it reasonably abates following menopause when these hormones decrease. In women in their reproductive years, adenomyosis can typically be managed with the goals to provide pain relief, to restrict progression of the process, and to reduce significant menstrual bleeding.
Usage of intrauterine device (IUD) with copper requires one IUD in each horn to be effective in case of bicornuate uterus. The same practice is generally applied when using IUD with progestogen due to lack of evidence of efficacy with only one IUD.
Evidence is lacking regarding progestogen IUD usage for menorrhagia in bicornuate uterus, but a case report showed good effect with a single IUD.
An estrogen-dependent condition, disease, disorder, or syndrome, is a medical condition that is, in part or full, dependent on, or is sensitive to, the presence of estrogenic activity in the body.
Known estrogen-dependent conditions include mastodynia (breast pain/tenderness), breast fibroids, mammoplasia (breast enlargement), macromastia (breast hypertrophy), gynecomastia, breast cancer, precocious puberty in girls, melasma, menorrhagia, endometriosis, endometrial hyperplasia, adenomyosis, uterine fibroids, uterine cancers (e.g., endometrial cancer), ovarian cancer, and hyperestrogenism in males such as in certain conditions like cirrhosis and Klinefelter's syndrome.
Such conditions may be treated with drugs with antiestrogen actions, including selective estrogen receptor modulators (SERMs) such as tamoxifen and clomifene, estrogen receptor antagonists such as fulvestrant, aromatase inhibitors such as anastrozole and exemestane, gonadotropin-releasing hormone (GnRH) analogues such as leuprolide and cetrorelix, and/or other antigonadotropins such as danazol, gestrinone, megestrol acetate, and medroxyprogesterone acetate.
The occurrence of all types of paramesonephric duct abnormalities in women is estimated around 0.4%.
A bicornuate uterus is estimated to occur in 0.1-0.5% of women in the U.S.
It is possible that this figure is an underestimate, since subtle abnormalities often go undetected. Some intersex individuals whose external genitalia are perceived as being male may nonetheless have a variably shaped uterus.
Polyps can be surgically removed using curettage with or without hysteroscopy. When curettage is performed without hysteroscopy, polyps may be missed. To reduce this risk, the uterus can be first explored using grasping forceps at the beginning of the curettage procedure. Hysteroscopy involves visualising the endometrium (inner lining of the uterus) and polyp with a camera inserted through the cervix. If it is a large polyp, it can be cut into sections before each section is removed. If cancerous cells are discovered, a hysterectomy (surgical removal of the uterus) may be performed. A hysterectomy would usually not be considered if cancer has been ruled out. Whichever method is used, polyps are usually treated under general anesthetic.
It is unclear if removing polyps affects fertility as it has not been studied.
Endometrial polyps are usually benign although some may be precancerous or cancerous. About 0.5% of endometrial polyps contain adenocarcinoma cells. Polyps can increase the risk of miscarriage in women undergoing IVF treatment. If they develop near the fallopian tubes, they may lead to difficulty in becoming pregnant. Although treatments such as hysteroscopy usually cure the polyp concerned, recurrence of endometrial polyps is frequent. Untreated, small polyps may regress on their own.
Cervical polyps can be removed using ring forceps. They can also be removed by tying surgical string around the polyp and cutting it off. The remaining base of the polyp can then be removed using a laser or by cauterisation. If the polyp is infected, an antibiotic may be prescribed.
99% of cervical polyps will remain benign and 1% will at some point show neoplastic change. Cervical polyps are unlikely to regrow.
Therapy involves both preventive measures and treatment of specific bleeding episodes.
- Dental hygiene lessens gingival bleeding
- Avoidance of antiplatelet agents such as aspirin and other anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen, and anticoagulants
- Iron or folate supplementation may be necessary if excessive or prolonged bleeding has caused anemia
- Hepatitis B vaccine
- Antifibrinolytic drugs such as tranexamic acid or ε-aminocaproic acid (Amicar)
- Desmopressin (DDAVP) does not normalize the bleeding time in Glanzmann's thrombasthenia but anecdotally improves hemostasis
- Hormonal contraceptives to control excessive menstrual bleeding
- Topical agents such as gelfoam, fibrin sealants, polyethylene glycol polymers, custom dental splints
- Platelet transfusions (only if bleeding is severe; risk of platelet alloimmunization)
- Recombinant factor VIIa, AryoSeven or NovoSeven FDA approved this drug for the treatment of the disease on July 2014.
- Hematopoietic stem cell transplantation (HSCT) for severe recurrent hemorrhages
While there is no cure for haemophilia, treatment improves outcomes.
Clotting factors are usually not needed in mild haemophilia. In moderate haemophilia clotting factors are typically only needed when bleeding occurs or to prevent bleeding with certain events. In severe haemophilia preventive use is often recommended two or three times a week and may continue for life. Rapid treatment of bleeding episodes decreases damage to the body.
Factor VIII is used in haemophilia A and factor IX in haemophilia B. Factor replacement can be either isolated from human blood serum, recombinant, or a combination of the two. Some people develop antibodies (inhibitors) against the replacement factors given to them, so the amount of the factor has to be increased or non-human replacement products must be given, such as porcine factor VIII.
If a person becomes refractory to replacement coagulation factor as a result of circulating inhibitors, this may be partially overcome with recombinant human factor VII.
In early 2008, the US Food and Drug Administration (FDA) approved anti-haemophilic factor, genetically engineered from the genes of Chinese hamster ovary cells. Since 1993 recombinant factor products (which are typically cultured in Chinese hamster ovary (CHO) tissue culture cells and involve little, if any human plasma products) have been available and have been widely used in wealthier western countries. While recombinant clotting factor products offer higher purity and safety, they are, like concentrate, extremely expensive, and not generally available in the developing world. In many cases, factor products of any sort are difficult to obtain in developing countries.
Clotting factors are either given preventively or on-demand. Preventive use involves the infusion of clotting factor on a regular schedule in order to keep clotting levels sufficiently high to prevent spontaneous bleeding episodes. On-demand (or episodic) treatment involves treating bleeding episodes once they arise. In 2007, a trial comparing on-demand treatment of boys (< 30 months) with haemophilia A with prophylactic treatment (infusions of 25 IU/kg body weight of Factor VIII every other day) in respect to its effect on the prevention of joint-diseases. When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group had a normal index joint-structure on MRI. Prophylactic treatment, however, resulted in average costs of $300,000 per year. The author of an editorial published in the same issue of the "NEJM" supports the idea that prophylactic treatment not only is more effective than on demand treatment but also suggests that starting after the first serious joint-related haemorrhage may be more cost effective than waiting until the fixed age to begin.
Treatment is almost always aimed to control hemorrhages, treating underlying causes, and taking preventative steps before performing invasive surgeries.
Hypoprothrombinemia can be treated with periodic infusions of purified prothrombin complexes. These are typically used as treatment methods for severe bleeding cases in order to boost clotting ability and increasing levels of vitamin K-dependent coagulation factors.
1. A known treatment for hypoprothrombinemia is menadoxime.
2. Menatetrenone was also listed as a Antihaemorrhagic vitamin.
3. 4-Amino-2-methyl-1-naphthol (Vitamin K5) is another treatment for hypoprothrombinemia.
1. Vitamin K forms are administered orally or intravenously.
4. Other concentrates include Proplex T, Konyne 80, and Bebulin VH.
Fresh Frozen Plasma infusion (FFP) is a method used for continuous bleeding episodes, every 3-5 weeks for mention.
1. Used to treat various conditions related to low blood clotting factors.
2. Administered by intravenous injection and typically at a 15-20 ml/kg/dose.
3. Can be used to treat acute bleeding.
Sometimes, underlying causes cannot be controlled or determined, so management of symptoms and bleeding conditions should be priority in treatment.
Invasive options, such as surgery or clotting factor infusions, are required if previous methods do not suffice. Surgery is to be avoided, as it causes significant bleeding in patients with hypoprothrombinemia.
Prognosis for patients varies and is dependent on severity of the condition and how early the treatment is managed.
1. With proper treatment and care, most people go on to live a normal and healthy life.
2. With more severe cases, a hematologist will need to be seen throughout the patient's life in order to deal with bleeding and continued risks.
For patients with vWD type 1 and vWD type 2A, desmopressin is available as different preparations, recommended for use in cases of minor trauma, or in preparation for dental or minor surgical procedures. Desmopressin stimulates the release of vWF from the Weibel-Palade bodies of endothelial cells, thereby increasing the levels of vWF (as well as coagulant factor VIII) three- to five-fold. Desmopressin is also available as a preparation for intranasal administration (Stimate) and as a preparation for intravenous administration. Recently, the FDA has approved the use of Baxalta’s Vonvendi. This is the first recombinant form of vWF. The effectiveness of this treatment is different than desmopressin because it only contains vWF, not vWF with the addition of FVIII. This treatment is only recommended for use by individuals who are 18 years of age or older.
Desmopressin is contraindicated in vWD type 2b because of the risk of aggravated thrombocytopenia and thrombotic complications. Desmopressin is probably not effective in vWD type 2M and is rarely effective in vWD type 2N. It is totally ineffective in vWD type 3.
For women with heavy menstrual bleeding, estrogen-containing oral contraceptive medications are effective in reducing the frequency and duration of the menstrual periods. Estrogen and progesterone compounds available for use in the correction of menorrhagia are ethinylestradiol and levonorgestrel (Levona, Nordette, Lutera, Trivora). Administration of ethinylestradiol diminishes the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary, leading to stabilization of the endometrial surface of the uterus.
Desmopressin is a synthetic analog of the natural antidiuretic hormone vasopressin. Its overuse can lead to water retention and dilutional hyponatremia with consequent convulsion.
For patients with vWD scheduled for surgery and cases of vWD disease complicated by clinically significant hemorrhage, human-derived medium purity factor VIII concentrates, which also contain von Willebrand factors, are available for prophylaxis and treatment. Humate P, Alphanate, Wilate and Koate HP are commercially available for prophylaxis and treatment of vWD. Monoclonally purified factor VIII concentrates and recombinant factor VIII concentrates contain insignificant quantity of vWF, so are not clinically useful.
Development of alloantibodies occurs in 10-15% of patients receiving human-derived medium-purity factor VIII concentrates and the risk of allergic reactions including anaphylaxis must be considered when administering these preparations. Administration of the latter is also associated with increased risk of venous thromboembolic complications.
Blood transfusions are given as needed to correct anemia and hypotension secondary to hypovolemia. Infusion of platelet concentrates is recommended for correction of hemorrhage associated with platelet-type vWD.
The antifibrinolytic agents epsilon amino caproic acid and tranexamic acid are useful adjuncts in the management of vWD complicated by clinical hemorrhage. The use topical thrombin JMI and topical Tisseel VH are effective adjuncts for correction of hemorrhage from wounds.