Pharmacokinetics of Oral Levonorgestrel in Women After Roux-en-Y Gastric Bypass Surgery and in BMI-Matched Controls

Abstract

Background Women are advised to primarily use non-oral contraceptive alternatives after Roux-en-Y gastric bypass since it is not known if the surgery affects the pharmacokinetics of oral contraceptives. Methods This is a multi-center, open label, phase 2 pharmacokinetic study performed at the University Hospital of Linköping and the Clinical Trials Center, Department of Obstetrics and Gynecology, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. Fifteen women aged 18–40 years who had previously undergone Roux-en-Y gastric bypass surgery and reached a BMI < 30 were included. Fifteen BMI-matched women with no previous history of Roux-en-Y gastric bypass surgery served as a control group. After administration of a single dose of a combined oral contraceptive containing 0.03 mg ethinylestradiol/0.15 mg levonorgestrel, serum levonorgestrel concentrations were determined during a 24-h period using ultra performance liquid chromatography/tandem mass spectrometry. The area under the plasma concentration time curve of levonorgestrel (AUC 0–24h ) was the main outcome measure. Results There were no significant differences in the studied pharmacokinetic parameters, AUC 0–24h , total AUC, peak serum concentration ( C max ), time to peak serum concentrations ( T max ), apparent oral clearances of levonorgestrel (CL oral ), or terminal half-lives ( t ½) between the groups. Conclusion This is to our knowledge the first study to evaluate the pharmacokinetics of oral levonorgestrel in women with a BMI < 30 at least 1 year after RYGB compared with a BMI-matched group of women. We could not find any significant pharmacokinetic differences between the groups, suggesting that oral levonorgestrel may be used in non-obese women after Roux-en-Y gastric bypass once a stable body weight has been reached. Clinical Trial Number EudraCT 2014–004677-17.

Adverse Neonatal and Obstetric Outcomes in a 20-year Brazilian Retrospective Cohort of Pregnancies after Bariatric Surgery

“…Almost one-third of women with unplanned pregnancies in our cohort were not under any contraceptive method, and another one-third were on an oral contraceptive. There is large and growing evidence of the controversy on the efficacy of oral contraceptives after RYGB, especially during the weight loss period [38]. Although we did not evaluate adherence and thus represent a possible bias, this method should be discouraged, which is the practice in our center nowadays.…”

Considerations for clinical evaluation of the effects of bariatric surgery on the pharmacokinetics of orally administered drugs

“…To minimize the bias from the follow-up period and type of surgery, only data with a follow-up period equal to or greater than 6 months after RYGB were included. Six types of drugs from 12 studies were selected ( Table 3 ) [ 13 14 15 16 18 19 20 21 22 23 24 25 ]. As mentioned above, the AUC of acetaminophen in Chen et al was analyzed in the AUC inf instead of the AUC last .…”

FSRH Guideline (August 2022) Progestogen-only Pills

“…There are theoretical concerns that both malabsorptive and restrictive bariatric procedures could decrease absorption of oral contraceptives 38,39. Evidence from two recent pharmacokinetic studies40,41 suggests that absorption of combined oral contraceptives (COCs) is not significantly affected by Roux-en-Y gastric bypass (RYGB). There is inadequate evidence to inform the effect of any type of bariatric surgery on contraceptive effectiveness of POPs 42–44…”