Effects of oral contraceptives on metabolic parameters in adult premenopausal women: a meta-analysis

Abstract

Objective: To estimate the effect of oral contraceptives (OC) containing different progestins on parameters of lipid and carbohydrate metabolism through a systematic review and meta-analysis. Patients and Methods: Premenopausal women aged 18 or older, who received oral contraceptives containing chlormadinone, cyproterone, drospirenone, levonorgestrel, desogestrel, dienogest, gestodene or norgestimate, for at least 3 months. Outcome variables were changes in plasma lipids, body-mass index (BMI), insulin resistance and plasma glucose. We searched MEDLINE and EMBASE for randomized trials and estimated the pooled within-group change in each outcome variable using a random effects model. We performed subgroup analyses by study duration (<12 months versus ˃=12 months) and polycystic ovary syndrome status. Results: Eighty-two clinical trials fulfilled the inclusion criteria. All progestins (except dienogest) increased plasma TG, ranging from 12.1 mg/dL for levonorgestrel (p<0.001) to 35.1 mg/dL for chlormadinone (p<0.001). Most progestins also increased HDLc, with the largest effect observed for chlormadinone (+9.6 mg/dL, p<0.001) and drospirenone (+7.4 mg/dL, p<0.001). Meanwhile, levonorgestrel decreased HDLc by 4.4 mg/dL (p<0.001). Levonorgestrel (+6.8 mg/dL, p<0.001) and norgestimate (+11.5 mg/dL, p=0.003) increased LDLc, while dienogest decreased it (-7.7 mg/dL, p=0.04). Cyproterone slightly reduced plasma glucose. None of the progestins affected BMI or HOMA-IR. Similar results were observed in subgroups defined by PCOS or study duration. Conclusion: Most progestins increase both TG and HDLc, their effect on LDLc varies widely. OC have minor or no effects on BMI, HOMA-IR and glycemia. The antiandrogen progestins dienogest and cyproterone displayed the most favorable metabolic profile, while levonorgestrel displayed the least favorable.

Comparison of two drospirenone-containing oral contraceptives for their effect on the ovary, menstrual cycle, acne, and side-effect profile: 20 µg ethinylestradiol/3 mg drospirenone (24/4) versus 30 µg ethinylestradiol/3 mg drospirenone (21/7)

“…Drospirenone increases HDL and TG, increases LDL with longterm use. While estrogens increase TG and HDL, they support LDL catabolism [20]. In a study comparing 24/4 tablets containing 20 mcg EE/3mg drospirenone with 21/7 tablets containing 20 mcg EE/150 mcg desogestrel, both tablets increased HDL while decreasing LDL [21].…”

The influence of combined oral contraceptive pills on carbohydrate metabolism in healthy women and in women with PCOS - a systemic review

“…Other trials showed that COCs do not have any influence on glucose as well as insulin levels and do not change HOMA-IR in women with higher levels of testosterone. However, in healthy women COCs increased the insulin level and HOMA-IR [32]. In some cases it was conlcuded that taking COCs does not have any influence on insulin resistance in women with PCOS [33].…”

“…The results of this study show that combined hormonal contraceptives do not cause clinically important changes in carbohydrate metabolism in women without diabetes. In "Effects of oral contraceptives on metabolic parameters in adult premenopausal women: a meta-analysis", which included 82 clinical trials by L. S. Sliva-Bermudez [32], the outcomes were similar-COCs have minor or no effects on HOMA-IR and glycemia. One of the studies, which included women with PCOS, was a meta-analysis that included 35 studies.…”

Sex differences and considerations for female specific nutritional strategies: a narrative review

“…During exercise, triphasic OC have been shown to decrease glucose flux and may reduce insulin action [ 64 ]. Lipid profiles may also be altered in women taking OC as a recent meta-analysis concluded that most progestins increase the concentrations of both triglycerides and high-density lipoprotein cholesterol, but effects on low-density lipoprotein cholesterol varied [ 65 ]. However, some have shown no difference in substrate utilization or hormonal response to 45-min of exercise at 65% VO 2 max in eumenorrheic women compared to women taking low-dose oral contraceptives [ 24 ], while others have shown increased glycerol appearance, indicative of triglyceride mobilization, and increased cortisol during exercise in women taking OC [ 66 ].…”