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Plasma concentrations of etonogestrel in women using oral desogestrel before and after Roux-en-Y gastric bypass surgery: a pharmacokinetic study
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN.
Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
Visa övriga samt affilieringar
2019 (Engelska)Ingår i: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 126, nr 4, s. 486-492Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective

To investigate whether Roux‐en‐Y gastric bypass (RYGB) affects oral desogestrel (etonogestrel) pharmacokinetics.

Design

Single centre, open label, phase‐2 pharmacokinetic study.

Setting

University hospital of Linköping, Sweden.

Population

Fourteen women with planned RYGB surgery were included; nine women aged 18–45 years using 75 micrograms desogestrel completed the study.

Methods

Steady‐state etonogestrel pharmacokinetic (PK) parameters were measured on three occasions for each individual (at 8 ± 6 weeks before surgery, and at 12 ± 2 and 52 ± 2 weeks after surgery). Each patient served as her own control. On each occasion, serum samples were collected during a 24‐hour period and etonogestrel concentrations were determined with ultra‐performance liquid chromatography/tandem mass spectrometry.

Main outcome measures

Area under the plasma concentration time curve of etonogestrel (AUC0–24 hours).

Results

All women had significant postoperative weight loss. There were no significant differences in AUC0–24 hours, terminal half‐lives (t½), time to peak serum concentrations (Tmax), or apparent oral clearances of etonogestrel (CLoral) before and after gastric bypass surgery on any occasion. Peak serum concentrations (Cmax) increased after 52 ± 2 weeks compared with preoperative values (0.817 ng/ml versus 0.590 ng/ml, P = 0.024).

Conclusion

To our knowledge, this is the first study to investigate the effects on desogestrel pharmacokinetics after RYGB. This study did not reveal any clinically significant changes in etonogestrel pharmacokinetics, suggesting that oral desogestrel may be used by women after RYGB surgery. The sample size was limited, however, and therefore the results should be interpreted cautiously.

Ort, förlag, år, upplaga, sidor
Wiley-Blackwell Publishing Inc., 2019. Vol. 126, nr 4, s. 486-492
Nyckelord [en]
Contraceptives; desogestrel; etonogestrel; gastric bypass surgery; hormonal contraception; obesity; oral contraceptives; pharmacokinetic; Roux-en-Y gastric bypass
Nationell ämneskategori
Gynekologi, obstetrik och reproduktionsmedicin
Identifikatorer
URN: urn:nbn:se:liu:diva-154831DOI: 10.1111/1471-0528.15511ISI: 000458702400012PubMedID: 30347490Scopus ID: 2-s2.0-85056623277OAI: oai:DiVA.org:liu-154831DiVA, id: diva2:1294597
Anmärkning

Funding Agencies|county council of Ostergotland (ALF)

Tillgänglig från: 2019-03-07 Skapad: 2019-03-07 Senast uppdaterad: 2025-02-11Bibliografiskt granskad
Ingår i avhandling
1. Contraception in women with obesity with special reference to gastric bypass surgery
Öppna denna publikation i ny flik eller fönster >>Contraception in women with obesity with special reference to gastric bypass surgery
2019 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2019. s. 75
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1677
Nationell ämneskategori
Gynekologi, obstetrik och reproduktionsmedicin
Identifikatorer
urn:nbn:se:liu:diva-156643 (URN)10.3384/diss.diva-156643 (DOI)9789176850961 (ISBN)
Disputation
2019-05-29, Berzeliussalen, Universitetssjukhuset, Linköping, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2019-05-02 Skapad: 2019-05-02 Senast uppdaterad: 2025-02-11Bibliografiskt granskad

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Ginstman, CharlotteFrisk, JessicaCarlsson, BjörnÄrlemalm, A.Hägg, StaffanBrynhildsen, Jan
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Avdelningen för barns och kvinnors hälsaMedicinska fakultetenKvinnokliniken i LinköpingInstitutionen för klinisk och experimentell medicinKirurgiska kliniken ViNAvdelningen för läkemedelsforskningKlinisk farmakologiInstitutionen för medicin och hälsa
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