Combined Hormonal Contraceptives
Combined hormonal contraceptives reduce menstrual blood loss by thinning the endometrium and possibly increasing factor VIII and von Willebrand’s factor levels. Combined hormonal contraceptives currently available include combined oral contraceptive pill (COC), transdermal contraceptive patches and vaginal rings. They provide reliable birth control and cycle control and reduce dysmenorrhoea and other menstrual complaints. In women with bleeding disorders, they have an added advantage of controlling ovulation bleeding and midcycle pain. Continuous use of these therapies (rather than the traditional 21-day course) is safe and can be used to control timing and frequency of menstruation as well as menstruation associated symptoms. This can be very useful for women with severe menstrual problems.
Most women who use combined hormonal contraceptives have none or very few side effects. Serious side effects of hormonal contraceptives include high blood pressure, liver abnormalities and clots. Women with bleeding disorders, however, may have a low inherited risk of clotting. Side effects that some women have are nausea, headaches, dizziness, breast tenderness and mood changes. Some of these side effects improve over the first 3 months. If the side effects continue the doctor may prescribe a different brand of hormonal contraceptive.
Levonorgestrel intrauterine system
Levonorgestrel intrauterine system (LNG-IUS, Mirena®) is the most effective medical treatment for menorrhagia and has been shown to be useful for reducing menstrual blood loss in women with bleeding disorders. It is also an effective and reversible method of contraception making it an ideal treatment for women with menorrhagia who want to preserve their fertility. The licensed duration of use in Ireland is 5 years i.e. once inserted it may stay in place for 5 years. The main problem is irregular bleeding or spotting, especially within the first 6 months. In women with bleeding disorders, there is a potential risk of bleeding at the time of insertion and preventative treatment with a haemostatic agent may be required.
Oral progestogens such as Medroxyprogesterone Acetate and Norethisterone are recommended treatments for menorrhagia when used as a 21-day course (days 5-26). Side effects include fatigue, mood changes, weight gain, bloating, depression, and irregular bleeding. In high doses, oral progestogens can be used with DDAVP or clotting factor to treat acute menorrhagia in women with bleeding disorders.
Progestin-only contraceptive such as Depo-Provera (Medroxyprogesterone Acetate) injections, Progestin-only pills, and the Implanon implant also reduce endometrial thickening and may reduce menstrual blood loss or stop menstruation. They are associated with a high rate of irregular bleeding and spotting. Insertion of the Implanon implant may also cause bleeding in women with bleeding disorders and preventative treatment with a haemostatic agent may be required.
Gonadotropin hormone (GnRH) analogues
These drugs stop ovulation and are effective for reducing menstrual flow and duration. Side effects due to reduced oestrogen include hot flushes and loss of bone density (which is reversible). GnRH analogues may be an alternative option to surgery for young women with resistant menorrhagia or severe bleeding disorders. If used for more than six months, hormone replacement therapy should be added to counteract low oestrogen levels.
Haemostatic therapy may be effective in controlling menorrhagia in women with bleeding disorders. Haemostatic agents constitute the main treatment option for women who are trying to conceive. They are also used in women who do not wish to get pregnant, either alone or in combination with hormonal therapy. Haemostatic therapies include DDAVP (1-desamino-8-D-arginine vasopressin), tranexamic acid and coagulation factor concentrates. Oral tranexamic acid also known as Cyclokapron is usually well tolerated but side effects include nausea, headache, and diarrhoea. Tranexamic acid stabilises a clot once it has formed by stopping the activity of an enzyme, called plasmin, which dissolves blood clots. [Note: A person with urinary tract bleeding (blood in the urine) should not take this drug.]
DDAVP can be given by intravenous injection or intranasally as a spray. For management of menorrhagia, it is usually administered as a nasal spray (150-300mcg daily for a maximum of 3-4 days, usually during days with the heaviest blood flow). Side effects include fast heart rate, flushing and headache. There is also a small risk of reduced sodium (salt) level and fluid retention. Therefore, fluid restriction during treatment is essential. If a person has a very bad headache or has not been able to urinate 24 hours after taking DDAVP, they should contact the Haemophilia Treatment Centre or Accident and Emergency for advice. In the elderly and in people with cardiovascular disease, Desmopressin can cause more serious side effects and may not be recommended. Both tranexamic acid and DDAVP alone or in combination may be effective in controlling menorrhagia in women with bleeding disorders. Regular prophylaxis with clotting factor replacement may be required to control menorrhagia in some women with severe factor deficiencies not responding to other treatments. These include plasma-derived factor concentrate or recombinant (genetically engineered) concentrate. All plasma used is screened for blood-borne viruses such as HIV, Hepatitis B and Hepatitis C and treated to inactivate any known viruses.
Surgery may be required in the presence of pelvic disease and for women who do not tolerate medical treatment or in whom this is unsuccessful. Women with inherited bleeding disorders are more likely to have peri-operative and/or delayed (7-10 days later) bleeding, even with relatively minor procedures such as hysteroscopy and biopsy. Therefore, any surgical intervention should be performed in a centre with available laboratory support and an experienced haematologist. Prophylactic treatment may be required pre-operatively to reduce the risk of excessive bleeding. Surgical options include hysterectomy and endometrial ablation. These procedures eliminate the possibility of future pregnancy and are only for women who do not want to have future pregnancy.
Hysterectomy is the surgical removal of the uterus, not including the removal of the ovaries and fallopian tubes. Haemorrhage is the most common complication. Others include genitourinary complications, infection, and poor wound healing. A lengthy post-operative recovery period is required. Long-term complications include early ovarian failure (premature menopause) and urinary and sexual problems. Perioperative bleeding complications are of specific concern in women with bleeding disorders. Therefore, hysterectomy should not be the first line treatment but used only when other treatments fail or when pelvic disease indicates its use in women who no longer wish to retain fertility.
Endometrial ablation techniques are now widely used as an alternative to hysterectomy. They may reduce menstrual blood loss in women with bleeding disorders. Endometrial ablation removes a thin layer of the lining of the uterus and stops the menstrual flow in many women. In some women, menstrual bleeding does not stop but is reduced to normal or lighter levels. These procedures have a shorter operating time, recovery time, and complication rate when compared to hysterectomy. Possible complications are:
• Cramping, like menstrual cramps for 1–2 days
• Thin, watery discharge mixed with blood, which can last a few weeks
• Frequent urination for 24 hours