Richard Lynen

Potential reduction in neural tube defects associated with use of Metafolin-fortified oral contraceptives in the United States

OBJECTIVE The objective of the study was to estimate the potential reduction of neural tube defects (NTDs) through the use of Metafolin-fortified oral contraceptives (OCs) in the United States. STUDY DESIGN A population-based decision analytic model was developed to estimate the benefits of increased red blood cell (RBC) folate levels through the use of Metafolin-fortified OCs on NTD risk during pregnancy. We modeled women who began the year taking Metafolin-fortified or traditional OCs. Folate levels were derived from the National Health and Nutrition Examination Survey and clinical trial data. NTD risk was estimated by applying a published risk equation to respective RBC folate levels. RESULTS The number of predicted NTD cases declined by 23.7% to 31.4%, depending on median baseline folate levels in women taking a fortified OC compared with taking a traditional OC. CONCLUSION Metafolin-fortified OCs have the potential to reduce the number of folate-dependent NTDs among current and recent OC users.

Ovarian cysts: presence and persistence with use of a 13.5 mg levonorgestrel-releasing intrauterine system

OBJECTIVE The aim of this study was to assess the presence of ovarian cysts in women using a new low-dose levonorgestrel-releasing intrauterine contraceptive system (LNG-IUS 13.5mg [total content]). STUDY DESIGN A Phase 3 study assessed LNG-IUS 13.5mg use in healthy women with regular menstrual cycles who requested contraception. Transvaginal ultrasonography was performed at screening, baseline, and 3, 6, 9, 12, 18, 24, 30, and 36 months after placement. RESULTS A total of 1432 women, mean age 27.2±4.8 years, were studied. A total of 10,446 transvaginal ultrasound examinations were performed over 3 years. Ovarian cysts were present in 1.6, 1.1, 2.3, 2.1, 2.4, 2.0, 2.1, 2.2, 1.9, and 2.1% of participants at screening, baseline, and Months 3, 6, 9, 12, 18, 24, 30, and 36, respectively. One hundred first-time ovarian cysts were identified from baseline through Month 9. The size distribution through Month 12 was ≤30 mm (13%), >30 to ≤50 mm (74%), >50 to ≤80 mm (11%), and >80 mm (0%). The overall persistence of ovarian cysts from one examination to the next in Year 1 was 12% (11/90 with follow-up). Cyst persistence was 36% from baseline to 3 months, 13% from 3 to 6 months, 10% from 6 to 9 months, and 0% from 9 to 12 months. The likelihood of cyst persistence increased for cysts >50mm (36%) as compared to those ≤50 mm (8%). CONCLUSION Ovarian cysts were present in 1.6% of women at screening, 2.0 to 2.4% of LNG-IUS 13.5mg users during Year 1, and 1.9 to 2.1% during Years 2 and 3. The majority were >30 to ≤50 mm in size. The small and diminishing number of persistent cysts-decreasing to 0% from 9 to 12 months-suggests that they were functional in nature. IMPLICATIONS Transvaginal ultrasound follow-up of women during a 3-year clinical trial of LNG-IUS 13.5mg showed that ovarian cysts were present in 1.6% of participants at screening and 1.1-2.4% at each subsequent visit. Eighty-eight percent were ≤5cm, with none >8cm. No ovarian cysts persisted beyond Month 9, suggesting a functional etiology.

Premenstrual dysphoric disorder symptom cluster improvement by cycle with the combined oral contraceptive ethinylestradiol 20 mcg plus drospirenone 3 mg administered in a 24/4 regimen

BACKGROUND A combined oral contraceptive comprising ethinylestradiol (EE) 20 mcg/drospirenone 3 mg in a 24/4 regimen has been clinically shown to alleviate the symptoms associated with premenstrual dysphoric disorder (PMDD). However, previous studies did not report data according to cycle-by-cycle improvement. STUDY DESIGN This was a subanalysis of a Phase III, double-blind, multicenter, United States-based study. Women with confirmed PMDD were randomized to EE 20 mcg/drospirenone 3 mg 24/4 or placebo for three treatment cycles. Ten of the 21 emotional and physical items on the Daily Record of Severity of Problems scale were grouped to define three symptom clusters: (a) negative emotions, (b) food cravings and (c) water retention-related symptoms. The change from baseline at each treatment cycle was compared between groups using a weighted analysis of covariance model. RESULTS The full analysis set comprised 449 women. Daily Record of Severity of Problems scores for each symptom cluster were significantly reduced from baseline with both EE 20 mcg/drospirenone 3 mg 24/4 and placebo (p<.0001 for all). The greatest symptom improvements were achieved within the first cycle of treatment and continued throughout cycles 2 to 3. The mean between-treatment difference was significant in favor of EE 20 mcg/drospirenone 3 mg 24/4 for all three symptom clusters in all three treatment cycles (p≤.0001 vs. placebo in percent change from baseline). CONCLUSION Ethinylestradiol 20 mcg/drospirenone 3 mg 24/4 improved commonly recognizable PMDD symptom clusters relating to negative emotions, food cravings and water retention-related symptoms to a significantly greater extent than placebo during all three cycles of treatment.

The prevalence of complications and healthcare costs during pregnancy

Abstract Objective: To study the economic burden of pregnancy in the US, common complications during pregnancy, and the incremental costs attributable to these complications. Methods: A retrospective comparative cohort study was conducted of pregnant women aged 15–49 years using de-identified medical and pharmacy claims from the Truven Health MarketScan Commercial Claims and Encounters database incurred between January 1, 2007 and December 31, 2011. The total healthcare costs are reported (adjusted to 2011 dollars) from the date of the first pregnancy-related claim through to 3 months post-delivery and these costs were compared to matched controls of non-pregnant women. Pregnancy-related complications were categorized, and the incremental costs associated with each complication were estimated using multivariate analyses. Results: A total of 322,141 eligible women with live births were studied. Compared to matched controls, the average costs of care for pregnant women were nearly

Bleeding pattern and cycle control of a low-dose transdermal contraceptive patch compared with a combined oral contraceptive: a randomized study.

13,000 higher through 3 months post-delivery. A total of 46.9% of women had at least one pre-specified pregnancy complication; the most commonly observed were fetal abnormality (24.7%) and early or threatened labor (16.3%). Multiple gestation (1.9%) resulted in the highest adjusted incremental cost (

The folate status of reproductive-aged women in a randomised trial of a folate-fortified oral contraceptive: dietary and blood assessments

12,212; 95% CI = 11,298, 13,216); hypertension (

Two-year continuation of intrauterine devices and contraceptive implants in a mixed-payer setting: A retrospective review.

6152; 95% CI = 5312, 6992) and diabetes (

Use of drospirenone/ethinyl estradiol (DRSP/EE) among women with acne reduces acne treatment-related resources.

5081; 95% CI = 4244, 5918) were also among those complications that led to high incremental costs of care. Conclusion: Pregnancy and delivery are frequently compounded by complications that lead to increased costs and resource utilization.

The Additional Cost Burden of Preexisting Medical Conditions During Pregnancy and Childbirth

OBJECTIVE(S) The aim of this study was to investigate the bleeding pattern and cycle control of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a combined oral contraceptive (COC) containing 0.02 mg EE and 0.1 mg levonorgestrel (LNG). STUDY DESIGN In this phase III, randomized, controlled, double-blind, double-dummy, multicenter trial, healthy women aged 18-45 years (smokers aged 18-35 years) received either the EE/GSD patch and a placebo tablet (n=171), or a placebo patch and the COC (n=175) for seven 28-day cycles. Bleeding control was assessed in two 90-day reference periods. RESULTS Mean number of bleeding/spotting days was comparable across treatment groups in both reference periods (p>.05). Mean number of bleeding/spotting episodes was also comparable in reference period 1; however, there were fewer bleeding/spotting episodes for COC in reference period 2 (3.4 versus 3.1; p=.01). Mean length of bleeding/spotting episodes was comparable across treatment groups for both reference periods (p>.05). Withdrawal bleeding occurred consistently in both groups over the entire treatment period, but its absence was more common in the COC group in cycles 4 and 6 of reference period 2 (p<.01). Intracyclic bleeding was comparable between groups. CONCLUSION(S) Bleeding pattern and cycle control with the EE/GSD patch was comparable to an EE/LNG-containing COC. IMPLICATIONS STATEMENT The findings suggest that bleeding patterns with the EE/GSD patch are similar to an EE/LNG-containing COC, except for absence of withdrawal bleeding, which was less common in patch users. The EE/GSD patch may constitute an additional contraceptive option for women.

Trends and regional variations in provision of contraception methods in a commercially insured population in the United States based on nationally proposed measures

OBJECTIVE To assess the folate status of US women in a study of a folate-fortified oral contraceptive (OC) using the Short Folate Food Frequency Questionnaire and plasma and red blood cell (RBC) folate samples. DESIGN Sub-analysis from a multi-centre, randomised, double-blind, controlled contraceptive trial with assessments at baseline and 6 months. We calculated dietary folate equivalents (DFE) consumed and the proportion of participants meeting folate adequacy benchmarks. SETTING Eight centres in the USA. SUBJECTS Healthy women aged 18-40 years requesting contraception with no contraindications for OC use. RESULTS Overall, 385 participants were randomised to either a novel folate-fortified OC or a marketed OC. The 262 (68 %) participants compliant with the protocol were included in the analysis set. Baseline daily DFE consumption was 529·8 (sd 342·1) μg and similar in both groups. At follow-up, the fortified OC group had higher intake than the conventional OC group (1225·9 (sd 346·2) μg compared with 500·6 (sd 361·2) μg). Mean plasma folate level increased from 44·5 (sd 17·2) to 55·8 (sd 21·1) nmol/l. Mean RBC folate level increased from 996·7 (sd 369·8) to 1311·9 (sd 436·0) nmol/l. The proportion meeting selected folate adequacy benchmarks increased in the fortified OC group (P < 0·001). CONCLUSIONS Lack of adequate folate intake in reproductive-aged women from dietary sources or supplements alone suggests the need for novel approaches. Use of folate-fortified OC ensures adequate folate levels and meeting of folate benchmarks.