Contraception in women with obesity with special reference to gastric bypass surgery

Background: The prevalence of obesity is increasing worldwide. The treatment of morbid obesity is dominated by bariatric surgery, for example Roux-en-Y gastric bypass (RYGB) surgery. If other contraceptive options are available, women with obesity should not be prescribed combined hormonal contraceptives due to the obesity-related increased risk of venous thromboembolism. Women are advised not to become pregnant during the first 12-18 months after RYGB surgery. There is a lack of knowledge of what type of contraceptive methods women with obesity are prescribed and whether they experience more or different side effects compared to normal-weight women. It is not known if the absorption and pharmacokinetic profile of progestins are affected by RYGB. The aim of this thesis was to investigate the pattern of contraceptive use in women with obesity, what type of contraceptive counselling was given to women in relation to RYGB, and whether the pharmacokinetics of two different progestins were affected by RYGB surgery. Material and Methods: Paper I is a retrospective cohort study analysing the patterns of contraceptive prescription, adverse effects, duration of treatment, reasons for discontinuation and bleeding pattern in 371 women with obesity compared with 744 normal-weight women. Medical records were scrutinised from 1 Jan 2010 until 31 Dec 2014. Paper II is based on a questionnaire sent to 987 women who had undergone RYGB during 2010. The questionnaire concerned preoperative and present contraceptive use, contraceptive counselling in relation to surgery and what type of recommendations they had received regarding pregnancy after RYGB. Papers III and IV are experimental studies investigating the pharmacokinetics of desogestrel (etonogestrel) and levonorgestrel in relation to RYGB. Results and conclusions: The most commonly prescribed contraceptive method for women with obesity was the progestin-only pill but many women with obesity were prescribed combined hormonal contraceptives despite the current recommendations of cautious prescription of oestrogen-containing methods. There were no differences in adherence to contraceptive method between women with obesity and normal-weight women. Despite the uncertainties regarding absorption, almost 10 % of women continued using oral contraceptives after RYGB. Nearly 40% were not aware of the recommendation to avoid pregnancy in the first year after RYGB and almost one third did not use any contraception during this period. This could be due to a lack of information or that the women did not retain the given information to avoid pregnancy. We found no clinically significant differences in the steady state pharmacokinetics of desogestrel before compared with after RYGB, or in single dose pharmacokinetics of levonorgestrel in women with BMI< 30 having undergone RYGB compared with BMI-matched non-operated women. This suggests that oral contraceptives containing desogestrel and levonorgestrel might be used after RYGB surgery

Patterns of prescription and discontinuation of contraceptives for Swedish women with obesity and normal-weight women

Purpose: This study aimed to explore the prescription of different contraceptive methods to Swedish women with obesity and to compare the pattern of prescription and adherence to treatment between this group and normal-weight women. Materials and methods: This study included 371 women with obesity and 744 matched normal-weight women, aged 18-40. Medical records were scrutinised for the period 1 January 2010 to 31 December 2014. The retrieved variables included: background characteristics, prescribed contraceptive methods, adverse effects, duration of treatment, reason for discontinuation and bleeding pattern. Result: Progestin-only pills were mainly prescribed to women with obesity (44% vs. 20%, p = 0.001) whereas combined hormonal contraception was mainly prescribed to normal-weight women (60% vs. 21%, p amp;lt; 0.0001). Thirty-three percent vs. 25% (p = 0.003) discontinued their contraceptive method within 1 year. The most commonly declared reason for discontinuation was bleeding disturbance (14.7% vs. 9.6%, p = 0.008). Conclusion: The most commonly prescribed contraceptive method in women with obesity was progestin-only pills, but surprisingly many women with obesity were prescribed combined hormonal contraception despite current Swedish and European guidelines. Incident users with obesity were significantly more likely to discontinue their contraceptive method within the first year of the study period, compared with incident normal-weight users.Funding Agencies|county council of Ostergotland [ALF] [LIO 601741, LIO 697051]</p

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

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 &lt; 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 (AUC0–24h) was the main outcome measure. Results There were no significant differences in the studied pharmacokinetic parameters, AUC0–24h, total AUC, peak serum concentration (Cmax), time to peak serum concentrations (Tmax), apparent oral clearances of levonorgestrel (CLoral), or terminal half-lives (t½) between the groups. Conclusion This is to our knowledge the first study to evaluate the pharmacokinetics of oral levonorgestrel in women with a BMI &lt; 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.Funding Agencies|Linkoping University; county council of Ostergotland (ALF) [LIO 601741, LIO 697051]</p