Is Reclassification of the Oral Contraceptive Pill from Prescription to Pharmacist-Only Cost Effective? Application of an Economic Evaluation Approach to Regulatory Decisions.

BACKGROUND AND OBJECTIVE: Unplanned pregnancies can lead to poorer maternal and child health outcomes. The Australian Therapeutic Goods Administration committee rejected reclassifying a range of oral contraceptive pills (OCPs) from prescription to pharmacist-only medicines in 2015, mainly based on safety concerns. Improving access to OCPs may encourage some women to use contraceptives or switch from other contraceptive methods. However, some adverse events may increase and some women may stop using condoms, increasing their risk of sexually transmitted infections. This study aimed to estimate the cost effectiveness of reclassifying OCPs from prescription to pharmacist-only. PERSPECTIVE: Healthcare system. SETTING: Australian primary care. METHODS: A Markov model was used to synthesise data from a variety of sources. The model included all Australian women aged 15-49 years (N = 5,644,701). The time horizon was 35 years. Contraceptive use before reclassification was estimated using data from the Household, Income and Labour Dynamics in Australia (HILDA) survey, while survey data informed use after reclassification. Health outcomes included pregnancies, pregnancy outcomes (live birth, miscarriage, stillbirth, ectopic pregnancy and abortion), sexually transmitted infections, adverse events (venous thromboembolism, depression, myocardial infarction and stroke), ovarian cancer cases and quality-adjusted life-years. Costs included those related to general practitioner and specialist consultations, contraceptives and other medicines, pharmacist time, hospitalisations and adverse events. All costs were reported in 2016 Australian Dollars. A 5% discount rate was applied to health outcomes and costs. RESULTS: Reclassifying OCPs resulted in 85.70 million quality-adjusted life-years experienced and costs of $46,910.14 million over 35 years, vs. 85.68 million quality-adjusted life-years experienced and costs of $50,274.95 million with OCPs remaining prescription-only. Thus, reclassifying OCPs was more effective and cost saving. However, a sensitivity analysis found that more research on the probability of pregnancy in women not using contraception and not trying to conceive is needed. CONCLUSION: Reclassifying OCPs is likely to be considered cost effective by Australian decision makers.

Oral contraceptive use and the ECG: evidence of an adverse QT effect on corrected QT interval.

BACKGROUND: A prolonged corrected QT (QTc) interval is a marker for an increased risk of sudden cardiac death. We evaluated the relationship between oral contraceptive (OC) use, type of OC, and QTc interval. METHODS: We identified 410,782 ECGs performed at Northern California Kaiser Permanente on female patients between 15 and 53 years from January, 1995 to June, 2008. QT was corrected for heart rate using log-linear regression. OC generation (first, second and third) was classified by increasing progestin androgenic potency, while the fourth generation was classified as antiandrogenic. RESULTS: Among 410,782 women, 8.4% were on OC. In multivariate analysis after correction for comorbidities, there was an independent shortening effect of OCs overall (slope = -0.5 ms; SE = 0.12, P < 0.0002). Users of first and second generation progestins had a significantly shorter QTc than nonusers (P < 0.0001), while users of fourth generation had a significantly longer QTc than nonusers (slope = 3.6 ms, SE = 0.35, P < 0.0001). CONCLUSION: Overall, OC use has a shortening effect on the QTc. Shorter QTc is seen with first and second generation OC while fourth generation OC use has a lengthening effect on the QTc. Careful examination of adverse event rates in fourth generation OC users is needed.

[Progestagen use in oral contraception - basic knowledge]. / Grundlagen zur Gestagen-Komponente in der hormonalen Kontrazeption.

The effects of most prostagens used in hormone replacement therapy (HRT) and in hormonal contraception are not identical. They differ in their structure, the metabolisation, their bioavailability and their partial activities. Therefore, it does not make any sense to declare that the different progestagens with their different profiles belong to one class of substances, having all the same effect. In function of their partial activities, progestagens are used today specifically for HRT, for hormonal contraception or as an anti-androgen. Because of their metabolic profile, some newer progestagens can be considered to be specifically favourable, such as Norpregnanes, Dienogest and Drospirenone. This review summarizes the properties and partial activities of progestagens used today and analyzes its clinical consequences.

[Use of oral contraceptives in the years 1994-2002: different but not less]. / Gebruik van orale anticonceptiva in de jaren 1994-2002: wel anders, niet minder.

OBJECTIVE: To describe the use of contraceptives among women aged 10-59, particularly in relation to the type of oral contraceptives (OCs) among starting users and women already using OCs. DESIGN: Descriptive. METHOD: Data on the use of medication in the period 1994-2002 by women in the age range 10-59 years were selected from the Interaction Database of North and East Netherlands. The study population was 33,795 women in 1994 and 102,894 in 2002. Cross-sectional studies were performed of prevalent and incident OC users per year and the contribution of the various types of OC was measured. RESULTS: The use of contraceptives among women aged 10-59 years has remained fairly constant since 1994, being about 33%. However, Dutch women started using OCs at an increasingly younger age: 47% of the 15-19-year-olds in 2002 compared with 35% in 1994. The use of third-generation OCs among young starting OC-users (10-19 years of age) in 2002 was very low (3.5% of all OCs). Among women who already used OCs, the switch from third- to second-generation OCs was less pronounced. In 2002, 23% of all OC-users used third-generation preparations compared with 46.5% in 1994. The proportion using cyproteron-ethinylestradiol increased slightly over the years. CONCLUSION: After 1994, mainly second-generation OCs have been prescribed. The switch from third- to second-generation OCs was especially marked among the young starting users. The use of cyproteron-ethinylestradiol increased slightly during the years.

Thromboembolic disease and present oral contraception.

Since their introduction, oral contraceptives have been linked to an increased incidence of thromboembolic events. Epidemiologic studies have shown that women who use third-generation oral contraceptives containing desogestrel, gestodene, or norgestimate have a higher risk of venous thrombosis than women who use second-generation oral contraceptives containing levonorgestrel. Women who use oral contraceptives are significantly less sensitive to activated protein C. From January 1996 to December 2001, 17,577 patients were hospitalized in our department, 177 of them (1%) had confirmed diagnosis of venous thromboembolism and 15 of those (177) were women on oral contraceptive therapy. Oral contraceptives were taken from 28 days to 18 months. No other potential congenital or acquired causes of thrombosis were present before thromboembolic events occurred in these women. The discontinuation of the pill combined with usual heparin (in one patient thrombolysis) and coumarin therapy was effective in all cases. After the discontinuation of coumarin (3-6 months), every patient was screened for hereditary thrombophilia. All women on oral contraceptive therapy had confirmed hereditary risk factors for venous thrombosis. Acquired resistance to activated protein C may explain the epidemiologic observation of increased risk of venous thrombosis in oral contraceptive users, especially in women using third-generation oral contraceptives who had other risk factors (hereditary or acquired) for venous thrombosis.

Myocardial infarction and third generation oral contraceptives: aggregation of recent studies.

BACKGROUND: Arterial cardiovascular and cerebrovascular adverse events associated with oral contraceptives (OC) are a major concern to the clinician. This paper aggregates the findings of seven recent oral contraceptive studies on the risk of acute myocardial infarction (MI) among users of second (2gen) and third (3gen) generation OC. METHODS: Odds ratios (OR) from seven original studies published between 1996 and 2001 underwent meta-analysis. They had accrued 6464 subjects since 1996. In addition, estimates of 22 studies published from 1965 to 1966 were synthesized using medians and ranges as an historical point of reference. RESULTS: Four meta-analyses were performed for each of the relevant comparisons. The point estimates for 3gen versus 2gen OC ranged from 0.44 (0.24-0.80) to 0.62 (0.38-0.99). Compared with non-users, the aggregated OR for 3gen OC was 1.13 (0.66-1.92); for 2gen OC it was 2.18 (1.62-2.94). CONCLUSIONS: This overview of seven controlled observational studies confirms that 3gen OC do not convey harm in regard to MI compared with non-users of OC. The aggregate data and the continuing replication of findings allow interpretation of benefit compared with older combined OC.

Biphasic versus monophasic oral contraceptives for contraception: a Cochrane review.

BACKGROUND: Side-effects caused by oral contraceptives discourage compliance with and continuation of oral contraceptives. Three approaches have been used to decrease these adverse effects: reduction of steroid dose, development of new steroids, and new formulas and schedules of administration. The third strategy led to the biphasic oral contraceptive pill. We compared biphasic oral contraceptives with monophasic oral contraceptives in terms of efficacy, cycle control and discontinuation due to side-effects. Our a priori hypotheses were: (i) biphasic oral contraceptives are less effective in preventing pregnancy than monophasic oral contraceptives, and (ii) biphasic oral contraceptives cause more side-effects, give poorer cycle control and have lower continuation rates. METHODS: We searched computerized databases Medline, Embase, Popline and the Cochrane Controlled Trial Register. Additionally, we searched the reference lists of all potentially relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the USA. We included randomized controlled trials comparing any biphasic oral contraceptive with any monophasic oral contraceptive when used to prevent pregnancy. We examined the studies found during the various literature searches for possible inclusion and assessed their methodological quality using the Cochrane guidelines. We contacted the authors of all included studies and of possibly randomized studies for supplementary information about the study methods and outcomes. We entered the data in RevMan 3.1, imported the data into RevMan 4.1, and calculated Peto odds ratios for the incidence of intermenstrual bleeding, absence of withdrawal bleeding and study discontinuation due to intermenstrual bleeding. RESULTS: Only one trial of limited quality compared a biphasic and monophasic preparation. This trial examined 533 user cycles of a biphasic pill (norethindrone 500 microg/ethinyl estradiol 35 microg for 10 days, followed by norethindrone 1000 microg/ethinyl estradiol 35 microg for 11 days) and 481 user cycles of a monophasic contraceptive pill (norethindrone acetate 1500 microg/ethinyl estradiol 30 microg daily). The study found no significant differences in intermenstrual bleeding, amenorrhoea and study discontinuation due to intermenstrual bleeding between the biphasic and monophasic oral contraceptive pills. CONCLUSIONS: Conclusions are limited by the identification of only one trial, the methodological shortcomings of that trial and the absence of data on accidental pregnancies. However, the trial found no important differences in bleeding patterns between the biphasic and monophasic preparations studied. Since no clear rationale exists for biphasic pills and since extensive evidence is available for monophasic pills, the latter are preferred.

[Effects of second and third generation oral contraceptives on hemostasis]. / Effecten van orale anticonceptiva van de tweede en de derde generatie op de hemostase.

Use of oral contraceptives induce changes in haemostatic parameters: changes occur in the procoagulant, anticoagulant, and fibrinolytic systems. The increased risk of venous thromboembolism with use of third, as compared with second generation oral contraceptives, found in epidemiological studies, has stimulated new research in haemostatic changes induced by both generations of oral contraceptives. A randomized crossover study showed that use of the third generation pill caused a greater increase of factor VII and prothrombin and a more pronounced decrease of factor V than the second generation pill. Acquired resistance to activated protein C (APC) was induced more strongly by preparations of the third than by those of the second generation. The concentration of protein S decreased markedly exclusively during use of the third generation pill, while it did not change during use of the second generation pill. The oral contraception-related effects on the anticoagulant system strongly resemble those of some forms of hereditary thrombophilia. If a woman with hereditary APC resistance (caused by factor V Leiden) uses oral contraceptives as well, and especially when she uses those of the third generation, she is subject to a considerable increase of the risk of venous thrombosis and becomes even more resistant to the anticoagulant action of protein C. In view of the epidemiological backgrounds of the difference in risk of thrombosis between second and third generation contraceptives, the second generation pill is recommended as the first choice for oral contraception.

Fuentes de información sobre los métodos anticonceptivos (con especial referencia a la anticoncepción oral): resultados de una encuesta española / Information sources on contraceptive methods. Results of a Spanish survey

Objetivo: Conocer las fuentes de información sobre los diferentes métodos anticonceptivos de la población femenina española en edad fértil (15-49 años).Material y métodos: Se realizó un muestreo aleatorio probabilístico, de tipo estratificado, de la población femenina española de 15 a 49 años y se procedió a encuestar a 2.136 mujeres que representan al total de las mujeres españolas en edad fértil. Los resultados se expresan en número de respuestas y porcentaje.Resultados: Más de la mitad de las mujeres españolas en edad fértil obtienen información sobre los diferentes métodos anticonceptivos en fuentes no médicas. Las mujeres más jóvenes (15-24 años) se informan, fundamentalmente, en su entorno social, aunque la familia representa un porcentaje bajo.Conclusiones: Parece necesario impulsar programas específicos de educación sexual en los colegios y universidades al mismo tiempo que emprender acciones dirigidas a la implicación activa de padres y médicos en la transmisión de información adecuada sobre los métodos anticonceptivos. (AU)

[Which contraception to choose for the diabetic woman?]. / Quelle contraception choisir pour la femme diabétique?

Low-dose oral contraceptives can be used by a great number of women with IDDM or a previous gestational diabetes mellitus. Others hormonal contraceptives (progestogen-only preparations) are less convenient and the compliance is poor with an increasing risk of gynaecologic side effects. The safety of this contraceptives as regards vascular diabetic complications is not evaluated well. Nulliparous patients with progressive complications can use barrier methods of contraception after education. Macroprogestative contraception is a adequate choice for women within forties. For multiparous diabetic women, intra-uterine devices represent the first choice.

Update on oral contraceptive pills.

Oral contraceptive pills are widely used and are generally safe and effective for many women. The World Health Organization has developed a risk classification system to help physicians advise patients about the safety of oral contraceptive pills. The choice of pill formulation is influenced by clinical considerations. By choosing appropriately from the available pill formulations, family physicians can minimize negative side effects and maximize noncontraceptive benefits for their patients. Additional monitoring and follow-up are necessary in special populations, such as women over 35 years of age, smokers, perimenopausal women and adolescents. Third-generation progestins are additional options for achieving noncontraceptive benefits, but their use has raised new questions about thrombogenesis. The U.S. Food and Drug Administration has labeled emergency postcoital contraception for use following unprotected coitus. Oral contraceptive pills are associated with few clinically significant drug interactions, although consideration of interactions remains important.

Eficacia y aceptabilidad en mujeres venezolanas de un anticonceptivo oral monofásico que contiene 20 microgramos de etinilestradiol y 150 microgramos de desogestrel / Efficacy and acceptability in Venezuelan females of a oral monophasic contraceptive containing ethynilestradiol 20 micrograms and desogestrel 150 micrograms

Evaluar la eficacia anticonceptiva, control de ciclo, aceptabilidad por parte de la usuaria, cambios en el peso corporal y tensión arterial con el uso de un anticonceptivo oral monofásico que contiene 20 microgramos de etilestradiol y 150 microgramos de desogestrel. Estudio abierto no comparativo multicéntrico donde participaron 122 mujeres proporcionando datos relativos a 600 ciclos. Ocho centros privados localizados en Caracas, Barquisimeto y Mérida. De las 122 mujeres evaluadas durante 600 ciclos, no se presentó embarazo, el control del ciclo tuvo una duración en todos los casos entre 3 a 5 y no huvo cambios estadísticamente significativos con respecto al peso corporal y tensión arterial. Los resultados derivados de este estudio sugieren que la reducción en la dósis de etinilestradiol a 20 microgramos permite todavía una máxima eficacia, buena aceptabilidad y un adecuado control de ciclo

Re-evaluation of oral contraceptive classifications.

Classification of combination oral contraceptives (OCs) by "generation"--typically based on the time of introduction of new compounds--is problematic. The estrogen and progestin components may be present in differing doses, and their interaction may therefore vary from one formulation to another. In addition, assigning the progestin component itself to a particular generation does not account for the unique characteristics of individual progestins within that group. These issues can be clarified by understanding the evolution of combination OCs in relation to dosage changes and by differentiating the pharmacologic profiles of individual progestins, particularly norgestimate, desogestrel, and gestodene. Although all sex steroids have the same basic structure, relatively minor structural modifications can cause dramatic alterations in biochemical activity. Progestational activity is the desired pharmacologic effect of progestins used in OCs, whereas androgenic activity, which increases the potential for adverse metabolic and physical side effects, is undesired. In vitro assays of the ability of various OC progestins to bind progestin and androgen receptors suggest that the androgen/progestin (A/P) binding ratio--a measure of progestin selectivity--is more favorable for norgestimate than for levonorgestrel, gestodene, or desogestrel. In vivo measurements of interactions between various progestins and human sex hormone binding globulin (SHBG) support the concept that generational classification of OC progestins is misleading. These compounds also differ clinically, as exemplified by differential effects on lipoprotein metabolism. In summary, progestins exhibit individually unique biochemical and clinical properties.

[Biological status of adolescent girls using estrogen-progestins]. / Statut biologique des jeunes filles sous oestroprogestatifs (OP).

Frequently adolescents use oral contraceptives (OP). Measures of some biological and metabolical patterns were performed in a sample of 339 young girls under going periodic health examination at Pasteur Institute in Lille. A case control study showed lower glucose level, and lower quantity of red blood cells and hemoglobin in OP users. Variance analysis showed lower GGT and TGO with "Gestodene", "Desogestrel" and "Norgestimate" than with the older progestatives (but cigarette smoking seems to influence these datas). Conclusion claims that new progestatives have the best biological tolerance.

Classification and comparison of oral contraceptives containing new generation progestogens.

New generation-oral contraceptives containing desogestrel or gestodene, and possibly also norgestimate, are more or less similar with respect to contraceptive efficacy, cycle control and acceptability. They also show a more favourable metabolic profile in comparison with older preparations. The desogestrel-containing preparations Gracial and Marvelon, and possibly also the gestodene-containing preparation Gynera, have demonstrated a good efficacy in well-controlled studies in the treatment of mild to moderate acne and/or hirsutism. There may be differences between new generation oral contraceptives with respect to their effects on metabolic variables like high-density lipoprotein cholesterol and sex hormone-binding globulin. These differences are most probably modulated by variations in both the pharmacokinetics and selectivity of the progestogenic components. Of particular relevance here may be the recent finding that approximately 20% of administered norgestimate is metabolized into levonorgestrel. For use in clinical practice, it is of considerable help to have different preparations containing a range of oestrogen doses with the same progestogen. They allow the clinician to 'tailor make' the choice of oral contraceptives for those starting pill use or those switching to another combination due to symptomatology or changed circumstances, e.g. advancing age, smoking, etc. In this respect, desogestrel-containing oral contraceptives allow the most flexible approach.