Toxic effects of the hormonal contraceptives (HCs)  are rare but potentially serious and require permanent termination of their use. HCs are contraindicated if there is a personal or family history of Porphyries, systemic lupus erythematosus, erythema nouex,  and polyarteritis nodosa.  Combined formulations favor the formation of delta-aminolevulinic acid and should be avoided in case of Porphyrie.  Drugs exposure can be a frequent precipitant of the acute attack in variegate porphyria;  whereas,  hormonal factors were more important in acute intermittent porphyria (p < 0.00001). 

Patients with acute intermittent porphyria also, show a trend to earlier and more frequent recurrent acute attacks following the initial admission ^(1,2). Acute intermittent porphyria is the most common type of porphyria.Its characteristic feature is periods of remissions and aggravations.

Aggravation or an attack of the disease may be caused by many endogenous and exogenous factors, among others by hormonal contraceptives. The attack included abdominal pain,  vomiting,  reduction in muscle strength in limbs and it was complicated by seizures caused by hyponatraemia. High excess haem precursors in urine was observed.  In a described case there were a few porphyrogenous factors whose action was observed,  among which the most important was desogestrel. ^(3,4) 

Due to this conclusion,  a change in contraceptive therapy that would exclude hormonal contraception was suggested.  Polyarteritis nodosa has been progressive illness resulting in a systemic necrotizing vasculitis which may affect the kidneys,  gastrointestinal tract,  skin,  nerves and muscles   ⁽⁵⁾.

Systemic lupus erythematous usually affects young women of reproductive age. Pregnancy may be possible if conception occurs during a stable remission of at least 6 months. 

Therefore,  it is mandatory to avoid the estrogens because of the high vascular risk and the possibility of an exacerbation of the disease.  Low-dose progestins or progestin-releasing IUDs appear the logical choose for these women ⁽⁶⁾. Focal nodular hyperplasia of liver is less dangerous than hepatic adenomas but still necessitate stopping use.

This pathological entity had been reported in women prior to widespread use of the pill, but HCs use appear to favor its growth and the development of subhepatic vein thrombosis or the Budd-Chiari syndrome, due primarily to the pill-estrogen content,as reported in sporadic cases ^(7,8). 

Estrogen-containing contraceptive methods are contraindicated in patients with acute liver diseases ⁽⁹⁾ Cerebral vein and sinus thrombosis is a relatively uncommon condition affecting young women,  that may occur in HC users affected by congenital thrombophilia, especially if prothrombotic conditions as nephrotic syndrome, hyperhomocysteinemia or if unknown dural Arteriovenous malformations   are   presents; however,  the   causal   relationship   is   not   well established ^(10,11). Fortunately, these findings are reported only in sporadic cases.

It is essential to provide the preventive diagnosis with the aim to avoid a probable high risk for the woman. The thrombotic risk, particularly of third-generation oral contraceptives use; was reported elevated among carriers of the factor V Leiden mutation ^{(a hereditary disorder in which activated factor V is inactivated by activated protein C-  APC)}.

This disorder is a common risk factor for venous thrombosis,which is associated with a 3-to 7-fold increased risk in heterozygous individuals. Rosing reported that oral contraceptives use lead to acquired activated protein C ^(APC)  resistance and women using third generation HC are more resistant to the anticoagulant action of APC than users of second-generation HCs ^(12,13).