Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters: conventional vs. extended-cycle use

Sänger, Nicole; Stahlberg, Skadi; Manthey, Torsten; Mittmann, Katrin; Mellinger, Uwe; Lange, Evelyn; Kühl, H.; Wiegratz, Inka

doi:10.1016/j.contraception.2008.02.005

Cited by 34 publications

(22 citation statements)

References 19 publications

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“…A rise in TBG results in the reduced clearance of tri-iodothyronine (T 3 ) and T 4 , thus increasing total T 3 and T 4 . COC use, however, appears to have little or no effect on physiologically active, free fractions of thyroid hormones14,24-26. Also, no significant changes in free T 4 or in TSH were observed in either group after six months of treatment, which is in agreement with results from other studies14-24-25.…”

Section: Discussionsupporting

confidence: 90%

“…In general, COCs suppress both ovarian and adrenal androgen synthesis, resulting in decreased levels of the androgen precursors androstenedione and DHEAS, as well as free and total testosterone26. The more pronounced drop in free testosterone relative to total testosterone in women receiving NOMAC/E2 is likely the result of the increase in SHBG, which was greater for NOMAC/E2 than for LNG/EE.…”

Section: Discussionmentioning

confidence: 98%

“…The increase in TBG as seen in the NOMAC/E2 group and to a greater extent in the LNG/EE group is also considered to be caused by the oestrogenic component of COCs15-25-26. As for CBG, the EE-induced, dose-dependent increase in TBG is generally not suppressed by progestogens, although a progestogen with androgenic activity may counteract this effect to some extent15.…”

Section: Discussionmentioning

confidence: 99%

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Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in comparison to one containing levonorgestrel and ethinylestradiol on markers of endocrine function

Ågren¹,

Anttila²,

Mäenpää-Liukko³

et al. 2011

The European Journal of Contraception & Reproductive Health

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ObjectivesTo compare the effects of two monophasic combined oral contraceptives, containing either nomegestrol acetate/17β-oestradiol (NOMAC/E2) or levonorgestrel/ ethinylestradiol (LNG/EE) on endocrine function, androgens, and sex hormone-binding globulin (SHBG).MethodsRandomised, open-label, multi-centre trial involving 121 healthy women, aged 18-50 years old. Participants received NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen (n = 60) or LNG/EE (150 μg/30 μg) in a 21/7-day regimen (n = 61) for six cycles. The primary outcome was the change from baseline to cycle 6 in markers of adrenal and thyroid function, androgens, and SHBG.ResultsTotal cortisol, corticosteroid-binding globulin (CBG), and thyroxine-binding globulin (TBG) increased from baseline in both groups, with significantly greater increases in the LNG/EE group. No relevant changes from baseline or differences between the groups were observed for thyroid-stimulating hormone (TSH) and free thyroxine (T4). Androgens and androgen precursors decreased from baseline in both groups, with significantly greater decreases in the LNG/EE group (except for free testosterone). A greater increase in SHBG was observed with NOMAC/E2 than with LNG/EE.ConclusionsNOMAC/E2 has significantly less influence on markers of adrenal and thyroid function and androgens than LNG/EE. The clinical relevance of these findings requires further study.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in comparison to one containing levonorgestrel and ethinylestradiol on markers of endocrine function

Ågren¹,

Anttila²,

Mäenpää-Liukko³

et al. 2011

The European Journal of Contraception & Reproductive Health

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“…These treatments often did not qualify for the subgroup analyses. The duration of treatment varied from 1 treatment cycle (Kuhnz et al ., 1991) up to 12 treatment cycles (Jung-Hoffman et al , 1988a; Åkerlund et al , 1994; Wiegratz et al , 1995; Sänger et al , 2008). Treatment was assessed for 6 cycles (the effect measure used for the meta-analysis) in 16 studies, 3 cycles in 14 studies and for 12 studies another time point had to be taken for the analyses.…”

Section: Resultsmentioning

confidence: 99%

“…cycle 2 (Days 12–14)Direct RIAIntra-assay CV: NRInter-assay CV: NRLLQ: NRMethod used is based on centrifugal ultrafiltration dialysis;calculated from a normogram constructed using serum SHBG and %FT (Hammond et al , 1980); free T can then be determined from T (Hammond et al , 2003)62 n = 24Mean (SD) age: 19.9 ± 1.3 yearsWeight/BMI: NR3 cycles25 EE/180-215-250 NGM, 21:7Legro et al (2008) 2 Randomized, double-blind, comparative, parallel groupHealthy womenNo OC: ≥3 monthsnormal menstrual cycle (21–35 days)non-smoking1 n = 31Mean (SD) age: 27.5 ± 4.7 yearsMean (SD) weight: 67.7 ± 13.9 kg6 cycles20 EE/1 mg NET 21:7Control cycle (Days 15–21) Tr. cycle 6 (days 15–21)Direct RIAIntra-assay CV: <10%Inter-assay CV: <10%LLQ: NR Not applicable7Sänger et al (2008) 2 Randomized, prospective, comparative, parallel groupHealthy women18–40 yearsRegular menstrual cycleNo hormonal contraceptives: ≥4 weeks1 n = 29 Mean (SD) age: 24.6 ± 3.2 yearsMean (SD) weight: 63.7 ± 8.0 kg12 cycles30 EE/2 mg DNG 21:7Control cycle (Days 21–26) Tr. cycle 4 (Days 19–21)CLIAIntra-assay CV: 4.6%Inter-assay CV: 7.4%LLQ: 0.07 nmol/lDirect RIAIntra-assay CV: 12.3%Inter-assay CV: 18.3%LLQ: 0.52 pmol/l7Duijkers et al (2010)Randomized, open-label, comparative, parallel groupHealthy women18–35 yearsNo hormonal contraceptives: not specified, but women using OC and only after return of spontaneous menses control cycle was started (= at least 2 cycles no OC)Control cycle: ovulation confirmed1 n = 32Mean (SD) age: 22.8 ± 3.3 yearsMean (SD) weight: 68.5 ± 12.3 kg6 cycles1.5 mg E2/2.5 mg NOMAC, 24:4Control cycle (Days 5–7) Tr.…”

Section: Resultsmentioning

confidence: 99%

The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis

Zimmerman

et al. 2013

Human Reproduction Update

244

151

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BACKGROUNDCombined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Although this suppressive effect has been investigated by numerous studies over many years, to our knowledge no systematic review concerning this issue had been performed. This systematic review and meta-analysis was performed to evaluate the effect of COCs on concentrations of total T, free T and SHBG in healthy women and to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T and free T.METHODSA review of the literature was performed using database searches (MEDLINE, EMBASE and the Cochrane Central Register of Clinical Trials) and all publications (from inception date until July 2012) investigating the effect of COCs on androgen levels in healthy women were considered eligible for selection. Three reviewers were involved in study selection, data extraction and critical appraisal. For the meta-analysis, data on total T, free T and SHBG were extracted and combined using random effects analysis. Additional subgroup analyses were performed to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T or free T.RESULTSA total of 151 records were identified by systematic review and 42 studies with a total of 1495 healthy young women (age range: 18–40 years) were included in the meta-analysis. All included studies were experimental studies and 21 were non-comparative. Pooling of the results derived from all the included papers showed that total T levels significantly decreased during COC use [mean difference (MD) (95% confidence interval, CI) −0.49 nmol/l (−0.55, −0.42); P < 0.001]. Significantly lower levels of free T were also found [relative change (95% CI) 0.39 (0.35, 0.43); P < 0.001], with a mean decrease of 61%. On the contrary, SHBG concentrations significantly increased during all types of COC use [MD (95% CI) 99.08 nmol/l (86.43, 111.73); P < 0.001]. Subgroup analyses revealed that COCs containing 20–25 µg EE had similar effects on total and free T compared with COCs with 30–35 µg EE. In addition, suppressive effects on T levels were not different when comparing different types of progestins. However, subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did show significant differences: COCs containing second generation progestins and/or the lower estrogen doses (20–25 µg EE) were found to have less impact on SHBG concentrations.CONCLUSIONSThe current literature review and meta-analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations. Due to the SHBG increase, free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T, but both affect SHBG. The clinica...

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Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception

Edelman

Gallo²,

Jensen

et al. 2005

Cochrane Database of Systematic Reviews

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Evidence from existing randomized control trials comparing COCs given continuously (greater than 28 days of active pills) to traditional monthly cyclic dosing (21 days of active pills and 7 days of placebo) is of good quality. However, the variations in type of pill and time length for continuous dosing make direct comparisons between regimens impossible. Future studies should choose a previously described type of pill and dosing regimen. More attention needs to be directed towards participant satisfaction and menstruation-associated symptoms.

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Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters: conventional vs. extended-cycle use

Cited by 34 publications

References 19 publications

Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in comparison to one containing levonorgestrel and ethinylestradiol on markers of endocrine function

Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in comparison to one containing levonorgestrel and ethinylestradiol on markers of endocrine function

The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis

Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception

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