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The First World Congress On:
Controversies in Obstetrics, Gynecology & Infertility |
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Hormonal Contraception for Young Adolescents – No
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The prescription of oral contraceptives can neither exclude the consideration of some potentially unfavourable metabolic side-effects relative to their use, nor the evaluation of the physiological or pathological traits and life habits of the young patient. In particular, the impact of contraceptives on coagulation, the immune system and hepatic function must be mentioned. From the foregoing considerations it is possible that absolute and relative contraindications may arise and define themselves and/or condition in which notwithstanding the absence of the use of oral contraceptives, an extremely careful and accurate monitoring is necessary. There are also conditions in which the use of oral contraceptives is not contraindicated, because it is not harmful for the patient, but in which the effectiveness of the pill may be reduced. This is the case of the use of oral contraceptives in combination with other drugs Contraindications Lupus erythematosus – The use of oral contraceptives is not advisable since it can further cause deterioration as the disease develops: numerous cases have been described of the onset of this disease in predisposed subjects while taking the pill, as well as cases with an aggravation of the symptoms or presenting a deterioration of the serological profile. LES is therefore an absolute contraindication. Conditions of elevated thromboembolic risk – An anamnesis of venous thromboembolism or a cerebral thromboembolic episode is a definite contraindication in the use of oral contraceptives. Congenital thrombophylic diathesis The risk of venous thromboembolism in relation to the intake of oral contraceptives is high in women who suffer from deficiency in physiological coagulation inhibitors: in women deficient in antithrombin III and taking estroprogestins, there is an increased incidence of thrombotic episodes, from 34/1000 to 275/1000 (2-4). Instead, protein C deficit carries a thromboembolic risk of 69/100 episodes per year per patient, which becomes 120/1000 under the pill (2-4). In a number of studies results regarding increase of thrombotic venous risk in women with protein S deficit are not homogeneous. The factor V Leiden mutation, which leads to resistance to activated protein C action seems to determine an increase in thrombotic risk varying from 5 to 30 times in different studies(8-9). in women with the G20210A prothrombin gene mutation, there is a relative increase in risk of about 16 times, independent of the type of contraceptive used (10). A thorough coagulation screening is mandatory in the presence of stroke, myocardial infarction or thromboembolic events in family members under 50 years of age. The possibility and cost-effectiveness of extending screening for high prevalence defects before the prescription of oral contraceptives is under debate (11). Acquired thrombophilic diathesis: The prevalence of acquired thrombophylic disease in the adolescent population is not known. Antiphospholipid antibodies have been found in certain autoimmune pathologies (coeliac disease). in patients with insulin-dependent diabetes, resistance to activated protein C occurs more frequently (12). Valvular heart disease: The use of the pill is discouraged in most valvular heart diseases due to increased risk of thromboembolism. Only in limited cases, with no repercussions on the haemodynamics and in agreement with the cardiologist, is it possible to use estroprogestins. (13). Immobilization – Surgery: In cases of surgery which may cause hypotension or require prolonged confinement as well as in operations on the lower limbs (even if simple as in operative arthroscopies), the use of estroprogestin compounds increases the risk of thromboembolism. Ideally the pill should be suspended at least four weeks before surgery and up to two weeks after complete rehabilitation; in actual practice all patients on the pill must add microheparinization prophylaxis without interrupting the intake of estroprogestins. In the presence of medullary lesions oral contraceptives are not advisable in situations of secondary immobilization. Multiple sclerosis is a contraindication in the use of oral contraceptives when the mobility is so reduced to increase thromboembolic risk (14). Headache – The intake of exogenous steroids has no effect on non- vascular or tension headache which is characterized by non-pulsating pain and accompanied by muscular contracture. Instead, migraine and vascular headaches produce mainly lateral pulsating pain; they are often associated with nausea, vomiting and photophobia, and are frequently family- or hormone-related. In 15 to 50% of such clinical cases, the use of estroprogestins may increase the intensity and frequency of headaches, which tend to occur in the week the compound is suspended. However, about 30% of the patients may even experience improvement. Therefore, for patients who tend to have headaches or a familial history of headaches, it is advisable to prescribe estroprogestins with 20 mcg of ethynilestradiol, together with a careful monitoring of number and type of headache occurrence during the first months of treatment. However, there are some contraindications to the use of the pill in these circumstances: • patients who use drugs which act as vasoconstrictors in cerebral circulation, including sumatriptan, zolmitriptan and ergotamine; • subjects with so-called ‘focal’ migraine, characterized by neurological symptoms including scotoma, scintillating scotoma, temporary hemianopsia, paresthesia, aphasia, hemiparesis and hemisensorial deficit, all of which precede the onset of headache and are contralateral to the source of pain. These are indicative of a vasospasm with temporary cerebral hypoperfusion this means increased risk of cerebrovascular pathology, according to some neurologists; • subjects with ‘crescendo’ migraines, lasting three or four days, with intensification of the symptoms. (15). Pathologies which Deteriorate with Oral Contraceptives Chorea – Estroprogestins are contraindicated in both benign chorea and Huntington’s chorea as they can cause the typical fits of spastic movements and contortions. (16). Otosclerosis – The use of estrogens is usually contraindicated in this case, but some audiologists allow use after surgery under strict audiometric monitoring. Pemphigoid – This blistery form of dermatitis with autoimmune pathogenesis may appear during pregnancy, but also after taking estroprogestins therefore prohibiting its use. Porphyria: Estrogens can set off an attack of porphyria in susceptible patients and are therefore contraindicated in patients with this disease. Bowel inflammatory diseases – There is an increased risk of thromboembolism in cases of exacerbation of Crohn’s disease or ulcerative colitis which contraindicate the pill. In non-acute situations contraindication is relative to the presence of frequent episodes of diarrhoea which limit the chances of sustained absorption of the product. Besides, it is known that Crohn’s disease (non-granulomatous type with colic localization) improves with the suspension of the pill (17). Liver disease – Subjects suffering from acute liver ailments, studied from the viewpoint of the modifications in the serum levels of hepatic enzymes, must not be treated with estroprogestins until at least three months after all hematic parameters have returned to normal. The presence of cholestatic jaundice and an increase in direct bilirubinemia, which can be attributed to excretion deficit of the hepatocytes (such as in the congenital Rotor and Dubin-Johnson syndromes), contraindicate pill use. Instead, in Gilbert’s syndrome, a benign congenital defect of bilirubina hepatic uptake which may present itself with minimal subicteri following fasting, heavy physical activity as well as fever, or with evidence of an increase in direct bilirubinemia, there are no contraindications against oral contraceptives, and there is often improvement (18). Cholelithiasis – Rare in healthy adolescents, it can be present in subjects with hemolytic anemia, cystic fibrosis, ileitis, anamnesis of pancreatitis, or in those patients who have undergone long-term therapy with thiazide diuretics. The earlier estroprogestins definitely increased the risk of biliar lithiasis, but this effect does not seem to develop with products which include 20 or 30 mcg of ethynilestradiol.(19, 20). Pathological Conditions Which Require Greater In-Depth Investigation Prior to Prescribing Oral Contraceptives Mitral prolapse: We intend the systolic dislocation of the valvular leaflets from their physiological position. In most cases the condition is genetically transmitted but does not show up before adolescence. More rarely, it may be a secondary condition (as in prolonged and significant anorexic states). The prescription of oral contraceptives is possible as long as the patient does not smoke, and the electrocardiogram does not indicate reflux, and a thorough coagulation screening comes out normal.(13). Insulin-dependent diabetes – In the diabetic adolescent the need to avoid an undesired pregnancy is especially important, because metabolic control, a necessary requirement in reducing risks for the fetus during pregnancy, may be particularly difficult in this age range. As a result, on one hand it is best to recommend that girls affected with this disease attempt to have a baby as soon as this fits in with their plans, and before significant complications in vascular and kidney functions arise. On the other hand, up to that time, it is extremely important to guarantee valid contraceptive protection. Although the pill is not the most appropriate method for everyone, we can point out that longitudinal studies on young diabetic women have shown that with the most up-to-date products, metabolic changes over an extended period remain unvaried when compared to controls. However, long-term studies of a representative adolescent group are not yet available. So diabetic girls can use products with 20 mcg of ethynilestradiol and progestins such as desogestrel or gestoden, keeping in mind the following criteria: • the presence of diabetes for less than 10 years; • careful management of glycemic control; • the absence of arterial, nervous, renal or retinal complications; • the absence of hypertension and obesity; • no smoking; • some physical activity; • a coagulation profile (including a PCR) within the norm; • the availability of seriated controls.(21, 22). Dyslipidemias – Compounds with desogestrel, gestoden and cyproterone acetate tend to modify the lipoprotein profile with an increase in the HDL cholesterol vs. LDL cholesterol ratio; this variation however does not usually emerge before six months of treatment and is more evident in compounds with 30 mcg of ethynilestradiol compared to those with 20 mcg. A slight increase in the synthesis of tryglicerides and VLDL depends instead on estrogens. In any case, a high hypertrygliceridemia can indicate an increased risk of thrombosis. The presence of hypercholesterolemia with an increase of the LDL fraction is instead not a contraindication and may respond favorably to treatment. Long-term monitoring of the lipoprotein pattern is however required. Splenectomy – This is not considered an absolute contraindication, but it requires careful monitoring of the platelet count. It is not advisable to take estrogens with readings over 500,000/mm3 Thalassemia – Thalassemic syndromes are characterized by a congenital defect of the synthesis of globin molecules, which reduces hemoglobin synthesis. The thalassemic trait in heterozygote subjects does not necessarily mean increased risk after taking the pill. In the light of progress being made in the treatment of homozygote subjects, it is not rare to find adolescents with beta thalassemia who continue to menstruate. The choice of using estroprogestins depends on general health and in particular on the presence of hyperbilirubinemia or gall stones, on hepatic function and on the number of platelets in circulation. Coeliac disease – Studies have shown that this disease does not necessarily indicate reduced absorption of steriods. The presence of antiphospholipid antibodies should be checked before prescribing the pill to subjects who have been diagnosed with this disease in the second infancy or during adolescence (23). Debate Over the Use of Oral Contraceptives Gynecological age: The best age for beginning treatment has been discussed in relation to the development of the hypothalamus-pituitary-ovarian axis which reaches maturity in most subjects a few years after menarche (24,25). Some Authors affirm that the onset of a regular menstrual cycle for a span of 12 to 18 months after the menarche indicates that complete maturation of the aforementioned axis has been accomplished (26). Other Authors retain that hormonal contraception can be given to subjects who have had three consecutive spontaneous menses (27). The age in which the attainment of bone mass peak is reached in young girls is another important question. We know that the maximal accumulation of bone mineral content takes place during the three years following the onset of the menarche (28). We do not know the optimal ethynilestradiol dosage to obtain the best bone mass. One study shows that oral contraceptives with 20 mcg of ethynilestradiol favour mantaining bone mineral density, but do not increase it (29). Prolactin-secreting adenoma: Despite being known for the stimulating physiological effect of estrogens on the prolactin-secreting cells, it is not certain that such a reaction is always produced in adenoma cells. So there are no definite elements to contraindicate the use of estroprogestins in a low dosage (EE < 30mcg) in subjects with prolactinoma (30). Endometriosis: Oral contraceptives have been widely used as symptomatic therapy for endometriosis, especially on a continuous basis, i.e. eliminating the suspension between twenty-one day dosages. In effect, various epidemiological studies have demonstrated that the pill temporarily inhibits endometrial foci, with a greater risk that the disease reappear once the pill is suspended (31). The prescription of oral contraceptives to girls with certain or suspected endometriosis should therefore be evaluated case by case, and placed in a broader therapeutic perspective. It must be kept in mind that estroprogestins are a valuable add-back therapy during Gn-RH analogs treatment beyond the classic 6 month period. (32). Epilepsy – Exogenous and endogenous steroids cause modifications in neuronal excitability, with progesterone moderating it and estrogens increasing it. However, controlled studies have not confirmed the preoccupation that the use of oral contraceptives may reduce control over epileptic seizures. Using compounds with 30 mcg of ethynilestradiol in epileptic patients is however limited by the possible effects of pharmacological interaction, since all anticonvulsants, except for sodium valproate, are potent enzymatic inductors on a hepatic level reducing the bio-availability of estroprogestins. The problem is further complicated by the theratogenetic potential of antiepileptics. (16) Drugs that May Reduce Effectiveness of Oral Contraceptives The main categories of drugs reducing the effectiveness of oral contraceptives are antibiotics, anticonvulsants and some tranquilizers. A detailed description is presented in the following table.  References 1) Gompel A, Kutten F, Mauvais-Jarvis P. Contraception chez la femme lupique. Ann Dermatol Venereol 115(3):367, 1988 2) Winkler UH, Zierleyn JP, Schulte H, Collet W, Schindler AE. Routine screening for coagulation inhibitors prior to prescribing the pill: prevalence data from a large cohort of German pill starters. Eur J Contracept Reprod Health Care 1(1): 47-52, 1996 3) Winkler UH. Activated protein C resistance and deficiencies of antithrombin III, protein C or protein S and the risk of thromboembolic disease in users of oral contraceptives. Eur J Contracept Reprod Health Care 3(2): 65-74, 1998. 4) Pabinger I., Schneider B.and the GTH Study Group on Natural Inhibithors: Thrombotic risk of women with hereditary Antitrombin III- Protein C and protein S- deficiency taking oral contraceptive medication. Thromb. Haemost. 71:548-553,1994. 5) Mannucci P.M., Valsecchi C., Krachmalnicoff A. et al. Familial dysfunction of protein S. Thromb. Haemost. 62: 763-766: 1989. 6) Heistinger M., Rumpl E., Iliasch H., et al. Cerebral sinus thrombosis in a patient with hereditary protein S deficiency: case report and review of the literature. Ann. Haematol. 64: 105-109, 1992. 7) Koelman J.H., Bakker C.M., Pladsoen W.C. et al. Hereditary protein S deficiency presenting with cerebral sinus thrombosis in an adolescent girl. J. Neurol. 239: 105-106, 1992. 8) Vandenbroucke J.P., Koster T., Breit E. et al. Increased risk of venous thrombosis in oral contraceptive users who are carriers of factor V Leiden mutation. Lancet 344: 1453-1457, 1994. 9) Hiller E., Pihusch R. Thrombophilia caused by congenital disorders of blood coagulation Fortschr. Med. 116 (29): 26-28: 1998. 10) Martinelli I., Taioli E., Bucciarelli P. et al. Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis. Arterioscl. Thromb. Vasc. Biol. 19: 700-703, 1999. 11) Palareti G., Legnani C., Frascaro M., Flamigni C., Gammi L, Gola G., Fuschini G., Coccheri S. Screening for activated Protein C resistance before oral contraceptive treatment: a pilot study Contraception 59:293-299, 1999 12) Pedersen O. D., Pederson K. R., Skouby S.O., Jespersen J. Oral contraceptives increase plasma resistance against activated protein C in women with insulin dependent diabetes mellitus In: Proc 15th World Congress on Fertility and Sterility, Montpellier 1995. 13) Elam MB, Viar M, Ratts TE, Chesney CM. Mitral valve prolapse in women with oral contraceptive-related cerebrovascular insufficency. Arch Intern Med 146:73-79, 1986 14) Villard-Mackintosh L, Vessey MP. Oral contraceptive and reproductive factors in multiple sclerosis incidence. Contraception 47:161, 1993
15) Guillebaud J. Oral contraception: the combined oral contraceptive In “Contraception: your questions answered”. Guillebaud J. Churchill Livingstone p.170, 1994. |
