Hormonal Contraceptives and Acne: A Retrospective Analysis of 2147 Patients.

INTRODUCTION: Although hormonal contraceptives may help acne or worsen it, there is limited evidence on the effects of many commonly prescribed agents. The present study evaluates patient-reported effect on acne from 2147 patients who were utilizing a hormonal contraceptive at the time of their initial consultation for acne.
METHODS: At the time of initial consultation for acne, each of 2147 consecutive patients using hormonal contraception provided her assessment of how her contraceptive had affected her acne. The Kruskal-Wallis test and logistic regression analysis were used to compare patient-reported outcomes by contraceptive type.
RESULTS: Depot injections, subdermal implants, and hormonal intrauterine devices worsened acne on average, and were inferior to the vaginal ring and combined oral contraceptives (COCs; P ≤ .001 for all pairwise comparisons), which improved acne on average. Within COC categories, a hierarchy emerged based on the progestin component, where drospirenone (most helpful) > norgestimate and desogestrel > levonorgestrel and norethindrone (P ≤ .035 for all pairwise comparisons). The presence of triphasic progestin dosage in COCs had a positive effect (P = .005), while variation in estrogen dose did not have a significant effect (P = .880).
CONCLUSIONS: Different hormonal contraceptives have significantly varied effects on acne, including among types of COC.

J Drugs Dermatol. 2016;15(6):670-674.

Impact of the sharp changes in the use of contraception in 2013 on the risk of pulmonary embolism in France.

BACKGROUND: In late 2012, a national pill crisis led French women to promptly change their behavior regarding contraception, with a significant increase in the use of first-generation and second-generation combined oral contraceptives to the detriment of third-generation and fourth-generation products (C3Gs and C4Gs). OBJECTIVE: To assess the impact of the sharp changes in 2013 on the rate of women hospitalized for pulmonary embolism in France. METHODS: All hospitalized pulmonary embolisms in women aged 15-49 years, excluding those occurring during delivery stay, were identified from the French national hospital discharge databases from 2010 to 2013. Hospitalization rates, overall and by age group, were calculated. We compared rates in 2013 with those in 2012, and with mean rates over the preceding 3-year period (2010-2012). Two populations of non-users of contraceptives were used as control groups: men aged 15-49 years, and women aged 50-69 years. The expected reduction in pulmonary embolism incidence, estimated by modeling the number of expected cases based on modifications of combined oral contraceptive exposure, was also considered. RESULTS: In France, in 2013 as compared with 2012, the pulmonary embolism hospitalization incidence rate in women aged 15-49 years fell by 10.6%, corresponding to a reduction of 322 hospitalizations (95% confidence interval -468 to -156). The expected pulmonary embolism reduction is consistent with the observed reduction in hospitalization incidence rate (-10.2% and -10.6%, respectively). Such a pattern was not observed in the control groups. CONCLUSIONS: The sharp change in contraception methods, with decreased use of C3Gs and C4Gs, probably played a major role in the reduction in venous thromboembolism morbidity in France.

Epidemiology of hormonal contraceptives-related venous thromboembolism.

For many years, it has been well documented that combined hormonal contraceptives increase the risk of venous thromboembolism (VTE). The third-generation pill use (desogestrel or gestodene (GSD)) is associated with an increased VTE risk as compared with second-generation (levonorgestrel) pill use. Other progestins such as drospirenone or cyproterone acetate combined with ethinyl-estradiol (EE) have been investigated. Most studies have reported a significant increased VTE risk among users of these combined oral contraceptives (COCs) when compared with users of second-generation pills. Non-oral combined hormonal contraception, such as the transdermal patch and the vaginal ring, is also available. Current data support that these routes of administration are more thrombogenic than second-generation pills. These results are consistent with the biological evidence of coagulation activation. Overall, the estrogenic potency of each hormonal contraceptive depending on both EE doses and progestin molecule explains the level of thrombotic risk. Some studies have shown a similar increased VTE risk among users of COCs containing norgestimate (NGM) as compared with users of second-generation pill. However, for this combination, biological data, based on quantitative assessment of sex hormone-binding globulin or haemostasis parameters, are not in agreement with these epidemiological results. Similarly, the VTE risk associated with low doses of EE and GSD is not biologically plausible. In conclusion, newer generation formulations of hormonal contraceptives as well as non-oral hormonal contraceptives seem to be more thrombogenic than second-generation hormonal contraceptives. Further studies are needed to conclude on the combinations containing NGM or low doses of EE associated with GSD.

Use of oral contraceptives in Germany: prevalence, determinants and use-associated health correlates. Results of National Health Surveys from 1984 to 1999.

OBJECTIVES: To describe oral contraceptive (OC) use, its determinants and use-associated health correlates from 1984 to 1999 in Germany. STUDY DESIGN: Cross-sectional comparison was performed for socioeconomic factors, personal lifestyle and use-associated health correlates between 1862 OC users and 2625 age-matched nonusers identified from five German National Health Surveys. Regression models were used to obtain the determinants of OC use. RESULTS: While in women aged 25-49 years OC use remained nearly constant in the western part of Germany from 1984 to 1999 (17.3-20.1%), it declined greatly in the eastern part from 43.0% in 1991 to 32.3% in 1999. Cross-sectional comparison and regression analysis suggested that OC users did not differ from nonusers in most selected personal and socioeconomic factors. OC users showed generally a better health profile than age-matched nonusers with more satisfaction with health, higher quality of life and no significant difference in history of cardiovascular diseases despite slightly higher prevalence of hypertension and hyperlipidemia that are of little clinical significance. CONCLUSIONS: OC use seems to be generally safe. Whether the better health profiles found in OC users are the results of OC use or effects of healthy users, or both, should be further studied.

Breast cancer and specific types of oral contraceptives: a large Norwegian cohort study.

The aim of our study was to examine the risk of breast cancer according to specific types of estrogens and progestagens in oral contraceptives (OCs) based on the prospective Norwegian Women and Cancer study (NOWAC). Between 1991-97 women aged 30-70 years were drawn at random from the central person register and mailed an invitation and a questionnaire. Women (102,443) were enrolled with follow-up information collected throughout 1999 by linkage with national registries of cancer, mortality and emigration based on the unique national identification number. Among the 96,362 women included in the present analysis 851 invasive breast cancer were diagnosed. The adjusted risk of breast cancer increased with 25% for ever use of OCs and the risk increased with increasing duration of use (test for trend: p = 0.007). No association between time since last use and breast cancer risk was found after stratification on duration of use. Positive trend was still found for total duration of use among women who used OCs more than 5 years ago. Second generation of OCs had an increased risk with increasing duration of use. Classifying progestagens according to chemical groups, the relative risk increased significantly with increasing cumulative dose of levonorgestrel progestagen. It was difficult to conclude for the other groups due to lack of power. In a multivariate analysis the cumulative dose for all progestagen groups were non-significant, although we observed a significant increased risk with increasing milligram-months of estrogen exposure (p = 0.002). In conclusion, the increased risk of breast cancer related with OC formulations could be due mostly to estrogen component.

Newer progestogens.

OBJECTIVE: To review the literature on the most recent progestogens to be developed, to provide clinical comparisons with older progestogens and to look at the potential of products not yet marketed. DATA SOURCES: Searches of Medline and Popline together with requests for bibliographies from the Population Council, Wyeth-Ayerst Research and Schering Health Care. STUDY SELECTION: Information from technical papers was used to ascertain the metabolic characteristics and receptor binding affinities of the compounds. Previous reviews were scrutinised in order to make comparisons with older compounds. Any available trials were examined to ascertain efficacy, bleeding patterns and tolerability, more weight being given to comparative trials. DISCUSSION: Five progestogens have been developed in the last decade. They are all devoid of androgenic activity; some have antiandrogenic activity. Combined oral contraceptive (COC) pills containing dienogest and drospirenone are already marketed. Nomegestrol and nestorone have been extensively studied as subdermal implants. CONCLUSIONS: Newer progestogens used in combination with oestrogen behave very similarly to existing products. Progestogen-only products using new progestogens have potential for significantly better tolerability due to their lack of androgenic activity.

Effect of second- and third-generation oral contraceptives on fibrinolysis in the absence or presence of the factor V Leiden mutation.

Third-generation oral contraceptives (OC) have been associated with an increased risk of venous thrombosis compared with second-generation OC. To find an explanation for this increased risk, the effect of a second- and third-generation OC and of the progestagens used in these pills on several fibrinolytic parameters was studied in the absence or presence of the factor V Leiden mutation. In a single-center, double-blind trial, 51 women without and 35 women with the factor V Leiden mutation were randomized to either a second-generation (30 microg ethinylestradiol/150 microg levonorgestrel) or a third-generation (30 microg ethinylestradiol/150 microg desogestrel) oral contraceptive. After two menstrual cycles of use and a wash-out period of two cycles, the participants received the corresponding progestagen-only preparation containing 150 microg levonorgestrel or 150 microg desogestrel. D-Dimers, thrombin-activatable fibrinolysis inhibitor (TAFI) and the clot lysis time in the absence (LYSmin) or the presence (LYSplus) of a blocking anti-factor XI antibody were determined in plasmas of the participating women, and the mean difference in changes between the OC were calculated. Both combined OC induced increased plasma levels of D-dimers and TAFI, and induced a prolongation of LYSplus, whereas LYSmin hardly changed. Virtually no changes in fibrinolytic parameters were observed for the progestagen-only preparations. No differential effects between levonorgestrel- and desogestrel-containing OC were found in women without factor V Leiden. Women with the mutation on levonorgestrel-containing OC showed an increased LYSplus compared with desogestrel containing OC (3.9; 95% confidence interval, 0.1-7.7). When using progestagen-only preparations, no differential effect on the fibrinolytic parameters were found, except for non-carriers on levonorgestrel who showed a reduced LYSmin compared with non-carriers on desogestrel (-4.0; 95% confidence interval, -7.8 to -0.2). In conclusion, the effect of oral contraceptives on fibrinolytic parameters is largely independent of the type of progestagen. The increased fibrinolytic activity during OC use appears to be induced by the estrogen component and may be counteracted by increased TAFI activation. This may result in an enhanced downregulation of fibrinolysis.

[Oral contraception and menopausal hormone replacement: effects on hemostasis and risk of venous thromboembolism]. / Contraception orale et substitution hormonale de la ménopause: effets sur l'hémostase et le risque thromboembolique veineux.

The estrogen component of oral contraceptives enhances both coagulation and fibrinolysis. These contradictory effects result in activation of coagulation and an increased risk of venous thromboembolism. The relative risk is about 4-fold as compared with a nonuser of the same age. However, the risk of deep vein thrombosis or pulmonary embolism attributable to the pill is small (2 cases per 10,000 users per year). Pills containing a progestagen of the so-called 3rd generation seem to increase the risk by an additional factor of 2. Though small, the risk of venous thromboembolism makes it necessary before any oral contraceptive prescription to take a thorough personal and family history (including risk factors) and to study the risk-benefit ratio on an individual basis. Moreover, patients should receive detailed information on the evaluation. Postmenopausal hormone replacement therapy does not induce significant hemostatic changes (especially with transdermal application) and is not associated with a proven risk of venous thromboembolism. Venous risk factors thus do not contraindicate the use of hormone replacement therapy, except perhaps in the immediate (one-year?) period after an acute event.

[Contraception for the diabetic woman]. / La contraccezione nella donna diabetica.

The various contraceptive methods available today are examined here: natural methods; sterilization; intrauterine devices; oral contraceptives. The analysis of the advantages and disadvantages of each of them indicates that in the diabetic woman low dosages of estrogen-progestins are the most suitable for short-term contraception since they do not seem to influence diabetic control. Once the patient has completed her family, the choice of method for long-term contraception is intrauterine devices or sterilization.

PIP: The menstrual cycle of the diabetic woman is irregular, therefore natural methods are not very reliable. Among male contraceptive methods vasectomy has the advantage of simplicity, requiring only local anesthesia. It does not require surgical intervention in the diabetic woman, but the disadvantage is its irreversibility. There have been numerous attempts with steroids, vaccines, and chemical substances, however, there is no contraceptive yet that is effective and harmless. Once the diabetic woman has achieved the desired family size, sterilization is more often used and it is safe. Sterilization should not be performed during cesarean section, especially not during preterm delivery. The route of choice is laparoscopy or the vaginal route. IUDs are not recommended for nulliparous women because of the possibility of tubal inflammation and hence the effect on fertility. Oral contraceptives (OCs) have shown a diabetogenic effect that has not been fully confirmed. This effect is attributed to the progesterone component. The risk of cardiovascular disease increases in diabetic patients during long-term use according to some studies. A 1991 study indicated that low-dose contraceptives used for 6 months by women with gestational diabetes did not provoke changes in the glucose tolerance test and the lipid profile. Similar findings were obtained in 100 women followed up for 5 years who had been implanted subcutaneously with silicone capsules containing 16 mg of levonorgestrel. The contraceptive vaccine could solve all these metabolic problems, however, research is still at the beginning. In sum, for short-term use in nulliparous women low-dose OCs are suitable, while for the long term the IUD or female or male sterilization is recommended.

[Indication-oriented prescription of hormonal contraceptives]. / Indikationsgerechte Verordnung hormonaler Kontrazeptiva.

A review about the different groups of oral contraceptives as monophasic combined pills, two-, triphasic and sequential preparations is given. Discussion of contraindications and advises for prescribing practice.

[The efficacy of Veinobiase in venous disorders presented in women taking estroprogesterone agents (a statistical study of 2,295 patients)]. / Efficacité de Veinobiase sur les troubles veineux présentés par des femmes sous estroprogestatifs (étude statistique réalisée chez 2,295 patientes).

The authors tryed by a statistical study to evaluate the efficacy of aphlebotinic therapy in venous diseases induced or aggravated by estroprogestative contraception. During this study, it emerged that the induced functional venous problems were quite virtually corrected by this treatment.

[The benefit of the classification of oral contraceptives. Studies of 525 women taking oral contraceptives (author's transl)]. / Nutzen der Klassifikation hormonaler Kontrazeptiva. Studie an 525 Frauen unter hormonaler Kontrazeption.

The multiplicity of oral contraceptives suggests a classification for clinical routine. From the dosage of estrogens and gestagens in oral contraceptives, aberration indices were calculated from consideration of proliferation and transformation aspects. According to these a classification of oral contraceptives into 3 "estrogen" groups and 4 "gestagen" groups was made. Such a classification was made in 525 women taking oral contraceptives which took into consideration the following parameters: age, length of time during which oral contraceptives had been taken, subjective side-effects, sexual medical and psychometric aspects.

[Directions for classification and indications of oral contraceptives (author's transl)]. / Hinweise zur Klassifikation und Indikation oraler Kontrazeptiva.

PIP: A method for classifying oral contraceptives based on functional criteria is described. Contraceptive preparations are classified according to the hormonal differences between the normal menstrual cycle and the cycle under hormonal treatment. These differences may be expressed as an "aberration index" based on temporal and hormonal differences between the normal and hormone-treated cycles. This index is calculated for seven common progestins, and use of the index values in prescribing contraceptives for women of specified physiological types is explained.^ieng