Hazardous prescription

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. 

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)

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