The classic antiepileptic drugs (AEDs) Phenytoin, Phenobarbital, Ethosuximide and Carbamazepine reduce contraceptive effectiveness by induction of hepatic cytochrome CYP450 enzymes, and also increase the capacity of sex hormone binding globulin (SHBG). Both estrogen and progesterone influence seizure activity in women with epilepsy, with estrogen generally demonstrating proconvulsant and progesterone anticonvulsant effects. While, hepatic enzyme inducers alter steroid metabolism in women receiving oral contraceptives, increase the risk for contraceptive failure, and interfere with calcium absorption and vitamin D metabolism, thus increasing the risk for osteoporosis and fractures.
Which contraception for women with epilepsy? Combined oral contraceptives (COC) containing a high progestin dose, well above the dose needed to inhibit ovulation, and to take the “pill” continuously (“long cycle therapy”).
But even with the continuous intake of a COC containing a higher progestin dose contraceptive safety cannot be guaranteed, thus additional contraceptive protection may be recommended during the anticonvulsivant therapy.
Adverse Effects of Hormonal contraception
- Cardiovascular Effects
- - Myocardial Infarction
- - Stroke
- - Arterial Accidents
- - Venous Thromboembolism
- - Blood Hypertension
- Other Effects
- - Angioedema
- - Peliosis Hepatis
- - Severe Adverse Ocular Reactions
- - Vasculitis
- Moderate adverse effects
- Cancer Risks
- - Breast cancer risk
- - Ovarian cancer risk
- - Endometrial cancer risk
- - Cervical cancer risk
- - Colorectal cancer risk
- - Skin cancer risk
- - Liver cancer risk
- - Pancreatic cancer risk
- - Neurofibromas growth
- - Unclear cancer risks
- Hazardous prescription
- Hormonal contraception in female transplant recipients
- - Hormonal contraception in female kidney recipients
- - Hormonal contraception in female liver transplant recipients
- - Hormonal contraception in female heart transplant recipients
- - Contraception in women HIV infected
- Mild Adverse effects
- New Perspectives immunocontraception
- Contraceptive counseling
Progestin-only pills (POPs) are likely to be ineffective, if used in combination with anticonvulsivant therapy. Subdermal progestogen implants are not recommended in patients on AEDs, because of published high failure rates. Depot medroxyprogesterone -acetate (DMPA) injections appear to be effective, however, they may not be first choice due to reported side-effects (intermenstrual bleeding, delayed return to fertility, impaired bone health). The use of intrauterine devices is an alternative method of contraception in the majority of women, with the advantage of no relevant drug-drug interactions. The levonorgestrel intrauterine system (IUS) appears to be effective, even in women taking AEDs.
Likelihood of serious side effects is low in the IUS users. Recommendation for women taking COC include possible use of noninducing AEDs as Valproic acid and some new AEDs (28,29,30).
Nevertheless, hormonal contraception confers comparable or superior efficacy compared with such other contraceptives as the intrauterine device and barrier methods and remains an appropriate option in women with epilepsy. (31)
Ethinylestradiol –containing formulations have been shown to unmasque LSE or trigger a crisis,and can induce unwilling metabolic and/or vascular effects (6,25). Initial manifestations or exacerbations of SLE are noted during the first six months after starting HCs.
However, seems that the incidence of disease flare-ups is the same ,as in patients not using HCs. However, the risk of side-effects of these preparations depend on the estrogen dose and the progestin type (32,33). In the meantime, it is mandatory to avoid combined hormonal contraception in SLE patients with high levels of antiphospholipid antibodies and, in those with active nephritis.
In fact, an observational study performed on SLE-affected women, using combined oral contraceptives (COCs) reported that 22% of those suffered from thromboses during use (St. Thomas’Hospital-London) (34,35) Progestagen- only contraceptives can lead to side-effects but do not seem to activate the disease (36). Considering that expression of progesterone receptors was found in 75% of neurofibromas, it was believed that hormonal contraceptive might promote their tumor growth.
This problem is very important in women affected from neurofibromatosis type1 (NF1). While, oral contraceptives do not seem to stimulate it.
However, prescription of high doses of synthetic progesterone can have this negative effect and deserve more caution (37). The combined hormonal contraceptives are absolutely contraindicated in women with acute liver and serious renal diseases (38,39,40).