Health Care Provider Attitudes Toward Safety of Selected Hormonal Contraceptives in Breastfeeding Women.

OBJECTIVES: Little is known about provider attitudes regarding safety of selected hormonal contraceptives among breastfeeding women. METHODS: Using a nationwide survey, associations were analyzed between provider characteristics and perception of safety of combined oral contraceptives (COCs) in breastfeeding women ≥ 1 month postpartum without other venous thrombosis risk factors and depot medroxyprogesterone acetate (DMPA) in breastfeeding women < 1 month postpartum and ≥ 1 month postpartum. RESULTS: Approximately 68% of public-sector providers considered COCs safe for breastfeeding women ≥ 1 month postpartum without other venous thrombosis risk factors, with lower odds among non-physicians versus physicians (adjusted odds ratios [aOR] range 0.34-0.51) and those with a focus on adolescent health/pediatrics versus reproductive health (aOR 0.68, 95% confidence interval [CI] 0.47-0.99). Most public-sector providers considered DMPA safe for breastfeeding women during any time postpartum, with lower odds among non-physicians versus physicians (aOR range 0.20-0.54) and those with primary clinical focus other than reproductive health (aOR range 0.26-0.65). The majority of office-based physicians considered COCs safe for breastfeeding women ≥ 1 month postpartum without other venous thrombosis risk factors, with lower odds among those who did not use, versus those who used, CDC's contraceptive guidance (aOR 0.40, 95% CI 0.21-0.77). Most office-based physicians also considered DMPA safe for breastfeeding women during any time postpartum. CONCLUSIONS FOR PRACTICE: A high proportion of providers considered use of selected hormonal contraceptives safe for breastfeeding women, consistent with evidence-based guidelines. However, certain provider groups might benefit from education regarding the safety of these methods for breastfeeding women.

Study design to evaluate the safety and effectiveness of hormonal contraception for women.

A discussion of the issues that affect the study design of hormonal contraception is presented, including ethical issues, measurement of contraceptive efficacy. Observational studies, experimental studies, and meta-analysis in hormonal contraception are also reviewed.

Contraception for midlife women.

Despite a decline in fertility, women of older reproductive age who do not desire pregnancy should use contraception until menopause. Unintended pregnancy can be disruptive at any age, but in older women, pregnancy is associated with higher rates of adverse health outcomes for the mother and the fetus because of advanced age and comorbid medical conditions (e.g., hypertension or diabetes). Therefore, providing appropriate contraceptive care to women of older reproductive age is critical.

Hormonal contraceptive methodology: an historical review.

The introduction of the first hormonal contraceptive was one of the most important events of the twentieth century for women. The availability of oral contraceptives (OCs) provided women with greater control over their reproductive lives. As OC usage steadily increased, so did concern over health risks associated with their use. Concluding that adverse events were dose-related, scientists sought to develop lower-dose formulations. In the four decades since the first OC, women seeking contraception have benefited from the development of non-oral hormonal delivery systems, including injectables, intrauterine devices, implants, a vaginal ring, and a contraceptive patch. It is hoped that this expanding menu of choices affords women opportunities to find methods better suited to their individual needs. Clinicians should continually evaluate their patients' hormonal contraceptive needs, and provide adequate counseling so that every woman is afforded the opportunity to achieve contraceptive success.

Prescribing oral contraceptives.

The combined oral contraceptive pill is the most popular method of contraception worldwide, with modern low-dose formulations significantly improving tolerability. Breakthrough bleeding is the most significant adverse event associated with the low-dose combined oral contraceptives. Monophasic, biphasic, triphasic and progestogen-only preparations are available, and the choice of formulation should be tailored to best suit the patient. Any areas of uncertainty or concern that the patient has should be addressed, and the patient should be clearly informed of how to use the oral contraceptive effectively, the likely initial adverse effects and what to do if a pill is missed.

Low-dose oral contraceptives and bone mineral density: an evidence-based analysis.

We reviewed studies of the association of oral contraceptive (OC) use and bone mineral density (BMD). We limited the review to studies of women using low-dose oral contraceptives and that measured BMD by bone densitometry. A total of 13 studies met the inclusion criteria. Nine of these showed a positive effect of OC use on BMD, and four did not show an association. However, none of the studies showed a decrease in BMD with OC use. We classified the level of evidence from each study according to the guidelines of the US Preventive Services Task Force. The level of evidence supporting a positive association between OC use and increased BMD is II-1. There is fair evidence (Category B) to support the position that OC use has a favorable effect on BMD. We made suggestions for a study design that could yield Level I evidence.

PIP: The authors reviewed studies of the association of oral contraceptive (OC) use and bone mineral density (BMD). They limited the review to studies of women using low-dose OCs and that measured BMD by bone densitometry. A total of 13 studies met the inclusion criteria; 9 of these showed a positive effect of OC use on BMD, and 4 did not show an association. However, none of the studies showed a decrease in BMD with OC use. They classified the level of evidence from each study according to the guidelines of the US Preventive Services Task Force. There is evidence supporting a positive association between OC use and increased BMD. There is fair evidence to support the position that OC use has a favorable effect on BMD. The authors made suggestions for a study design that could yield level I evidence.

Interrelationship of serum levonorgestrel and sex hormone-binding globulin levels following vaginal and oral administration of combined steroid contraceptive tablets.

Ten women were treated daily with a standard dose contraceptive tablet containing 0.25 mg levonorgestrel (LNG) in combination with 0.05 mg ethinylestradiol. Five women used the tablet vaginally, while the other five used it orally. Blood samples were taken at frequent intervals on the first day of treatment and after 1 and 2 hours on treatment days 7 and 14. Serum LNG levels were measured by radioimmunoassay, and sex hormone-binding globulin (SHBG) was quantitated by charcoal assay. On day 1, peak concentrations of LNG (5.1 ng/ml) occurred within 2 hours in the oral group, whereas in the vaginal group a peak of 2.2 ng/ml was reached after 4 hours. After 24 hours, mean serum concentrations of LNG were 1.1 and 0.69 ng/ml in the oral and vaginal groups, respectively. In both groups, mean LNG concentrations increased dramatically on days 7 and 14 compared to day 1. There was no significant difference between the two groups in LNG concentrations, except after 2 hours on day 1. SHBG levels were increased after one day of treatment. By day 14 of treatment, there was a 3.5- to 4.5-fold rise in SHBG levels from pretreatment values in both groups. However, there was no significant difference in SHBG levels between the two groups throughout the study. A high correlation was found between serum levels of SHBG and LNG in both the vaginal and oral groups. The results suggest that the increase in serum LNG levels in women receiving combined contraceptive tablets either vaginally or orally is due to increased levels of SHBG. Also, the measured concentrations of LNG in the vaginal group are consistent with the previously reported clinical contraceptive efficacy of combined contraceptive tablets administered vaginally.

An open-label, multicenter study to evaluate Yasmin, a low-dose combination oral contraceptive containing drospirenone, a new progestogen.

This open-label, multicenter study evaluated the efficacy, safety, and cycle control of Yasmin, a new low-dose, monophasic oral contraceptive containing the unique progestogen drospirenone (DRSP) 3 mg and ethinyl estradiol (EE) 30 microg. DRSP is a synthetic progestogen that has antiandrogenic and antimineralocorticoid effects. In this study, 326 women were evaluated and 220 (67%) completed all 13 treatment cycles. The corrected Pearl Index was 0. 407. Of the 151 subjects who experienced intermenstrual bleeding at any time during the study, the majority (64%) had bleeding during only one or two pill cycles. Breakthrough bleeding without spotting occurred in 1% of all cycles, spotting without breakthrough bleeding in 9.3% of all cycles, and breakthrough bleeding with spotting in 3% of all cycles. Amenorrhea was observed in 3% of all cycles. In all, 20 subjects (6%) discontinued participation in the study because of adverse events. No serious adverse events related to the study drug were reported. No clinically significant changes in weight, blood pressure, or lipids were reported. The impact of the new progestogen DRSP on the women's self-perception of menstrual health was also evaluated. Subjects reported that symptoms of water retention, negative affect, and increased appetite significantly improved at cycle 6 from baseline. This study demonstrates that Yasmin is an effective oral contraceptive that is safe and well tolerated.

Oral contraception: current use and attitudes.

Oral contraception (OC) has been available for almost four decades. During this time, changes in contraceptive use in general and OC in particular have occurred. Knowledge and attitudes about OC may not always reflect trends in use. Contraceptive use data from 1965-1995 show that OC continue to be the method chosen consistently by more than one-quarter of women contraceptors. Probably even more women would use the pill if they had more accurate information regarding the higher failure rates with barrier methods (especially the condom), if misperceptions about OC safety were put to rest, and if greater awareness of the noncontraceptive health benefits of OC could be achieved. Increased education and awareness of women as well as their healthcare providers has the potential to positively affect future contraceptive use.

PIP: During the four decades that oral contraceptives (OCs) have been available to US women, important changes have occurred in their use patterns. The mass media, health care providers, and health insurance companies all have shaped these patterns. The media continue to emphasize the health risks of OC use, despite the fact that changes in the steroid content of OCs and identification of patient risk factors have eliminated or minimized many adverse outcomes. Educational efforts by health care providers on the noncontraceptive benefits of OC use have been inadequate to counteract media-promoted public misperceptions. Inaccurate information may lead women to select a method that lacks the appropriate degree of effectiveness and a consequent increased risk of unintended pregnancy. Two measures of socioeconomic status--income and education--exert a major influence on the choice of a contraceptive method by US women. Low-income women with a high school education or less are more likely to use female sterilization and less likely to use OCs than women with more education and income. Future contraceptive trends in the US will depend on factors such as the changing age distribution of women, revised upper age limits for OC use, the effects of delayed childbearing and sterilization, the impact of new methods, the availability of abortion, and concerns about HIV infection and other sexually transmitted diseases.

Improving patient educational literature: an understandable patient package insert for "the pill".

The objective of this project was to develop a simpler, more understandable, and accurate patient package insert (PPI) for inclusion in all packs of oral contraceptives (OCs). The project involved field-testing, using focus groups and semistructured cognitive interviews with family planning patients, a self-administered survey of clinic staff, and written recommendations from oral contraceptive and readability experts. The revision and field-testing of the PPI reduced its length by one third, lowered its reading level from the 10th to 1 2th grade down to 6th grade, included lay as well as medical terminology, and reorganized the information to make it easier to find and easier to use. The revised PPI, as submitted to the FDA in February 2001, could increase patient knowledge of safe and effective pill use and would be a valuable educational tool for providers of oral contraceptives. The FDA is currently updating the OC product labeling to reflect the most recent safety data and will then issue the labeling, including the field-tested patient package insert, for public comment.

[Contraceptive methods and adequacy of hormonal oral contraceptive use in the city of Pelotas, Rio Grande do Sul, Brazil: 1992-1999]. / Uso de métodos anticoncepcionais e adequação de contraceptivos hormonais orais na cidade de Pelotas, Rio Grande do Sul, Brasil: 1992 e 1999.

A cross-sectional study was conducted to assess contraceptive methods and the adequacy of oral contraceptive use by women aged 20 to 49 years in the city of Pelotas. The results were compared with another cross-sectional study performed in 1992. A sample was randomly selected, including 766 women aged 20 to 49 years. Some 495 of the sample (64.6%) used a contraceptive method, in the following order: oral contraceptives (55.4%), surgical sterilization (22.2%), condoms (10,5%), and IUD (7.7%). Among users of oral contraceptives, 62 (22.2%) had some contraindication. Incorrect use of contraceptive methods was associated with age but not with socioeconomic status. As compared to the previous study, there was a reduction in the use of oral contraceptives. Meanwhile, other methods such as surgical sterilization, condoms, and IUD were used more frequently than in 1992.

[A review of international clinical experience with a low-oestrogen oral contraceptive (author's transl)]. / Ubersicht internationaler klinischer Erfahrungen mit einem östrogen-niedrig-dosierten oralen Kontrazeptiveum

PIP: 854 women received C49'249-Ba for contraceptive purposes over a total of 4478 cycles (average 5.3 cycles each patient). No pregnancies occurred during the treatment. 50% of the women tolerated the drug without any undesirable side effects. 8% of the women discontinued treatment because of negative side effects. 26 negative side effects were reported in 309 (36.6%) of the patients, in a total of 766 (17.1%) cycles. Amenorrhea was observed in 4.1% of the women in 1.3% of the cycles. 24.4% of the patients reported bleeding disorders. Other symptoms were nausea (7.4% of the cycles), fatigue (2.4%), headache (5.4%). Weight gains, elevated blood pressure, libido changes, and disorders in liver, blood coagulation, or lipid serum were slight. Most of these undesired side effects appeared in the early cycles of therapy and decreased or disappeared after continuation of the treatment. Pregnanediol tests showed that the contraceptive effect of C49'249-Ba occurs through changes in the cervix mucus membrane, endometrium as well as by means of ovulation inhibition. In spite of the low estrogen dose, this preparation offers reliable contraceptive protection.^ieng

Reduced community access to a key contraceptive: public health consequence from false suspicion of HIV-contaminated injectables.

BACKGROUND: This study was conducted to investigate a report of positive test results with DMPA on an HIV rapid test. Suspecting HIV contamination, the Zambian Ministry of Health initiated a product withdrawal pending full evaluation. STUDY DESIGN: DMPA was evaluated for compliance to product specifications. Contamination with HIV and blood components was investigated with PCR and human IgG ELISA. The performance of Genie II, Unigold and Determine HIV rapid tests was evaluated using DMPA. RESULTS: DMPA was found compliant with product specifications and negative for HIV and human IgG. DMPA impaired the performance of HIV rapid tests resulting in false-positive/indeterminant results. Rapid test results using polysorbate 80 (formulation component of DMPA) mimicked results obtained with DMPA. CONCLUSIONS: The DMPA sample was negative for HIV and human IgG. Formulation components may have led to the interpretation of false-positive results, reinforcing the need to validate the sample type used in any test. DMPA use was reinstated in Zambia, minimizing the public health impact that resulted from the initial rapid test results.

Evaluating the safety of medicines, with particular reference to contraception.

Toxicological studies and clinical trials cannot be expected to predict all important adverse effects of medicines and contraceptives. Post-marketing surveillance is essentially an epidemiological task that involves detecting associations between drugs and events. The first alerts about drug safety problems have often come from case reports, but epidemiological studies are needed to confirm adverse (or beneficial) effects and to provide quantitative information. This article illustrates methodological principles by considering three examples from the field of contraceptive safety: oral contraceptives and breast cancer, intrauterine contraception and pelvic inflammatory disease, and newer oral contraceptives and venous thromboembolism. Key issues that emerge include bias and confounding, the place of subgroup analyses, random error, and the use of computerized databases. In research on contraceptive and drug safety, conclusions usually need to be based on careful assessment of multiple observational studies.

[The value of the gingival cytogram for the evaluation of hormonal contraceptives]. / Zur Bedeutung des Zytogramms der Gingiva für die Bewertung hormonaler Kontrazeptiva.

The results obtained from the cytological examination of gingival smears taken during one cycle demonstrate that the effect of the depot contraceptive Deposiston on the gingivae is measurable.

PIP: Cytological smears of the gingiva were taken from 14 women who used the depot preparation Deposiston for 12 cycles. A temporary increase in the keratinization and karyopyknosis indices was observed shortly after the 1 mg ethinyl estradiol tablets were taken in the first three weeks of the treatment cycle. These indices decreased markedly at the beginning of the 4th week after the 10 mg norethisterone acetate tablet was taken.