Does Diane 35 (cyproterone acetate and ethinyl estradiol) increase triglyceride levels in the blood?

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From the Guidelines

Diane 35 (cyproterone acetate and ethinyl estradiol) can increase triglyceride levels in the blood, as evidenced by the estrogen component, ethinyl estradiol, which is known to elevate triglycerides 1. The increase in triglyceride levels is generally dose-dependent, with higher estrogen doses causing greater elevations.

Mechanism and Effects

The triglyceride-raising effect of ethinyl estradiol occurs because it enhances hepatic triglyceride production and reduces clearance from the bloodstream. For most women with normal baseline triglyceride levels, this increase remains within acceptable limits. However, women with pre-existing hypertriglyceridemia or a family history of lipid disorders may experience significant elevations that could potentially increase cardiovascular risk or, in rare cases, lead to pancreatitis.

Clinical Considerations

For this reason, women taking Diane 35 should have their lipid profiles monitored, particularly those with existing risk factors. Alternative treatments might be considered for women with severely elevated baseline triglycerides (>500 mg/dL) or those who develop significant elevations while on the medication. It's also worth noting that the progestin component, cyproterone acetate, may have some ameliorating effects on the estrogen-induced hypertriglyceridemia, but the overall impact of Diane 35 on triglyceride levels is still a concern 1.

Recent Studies

A recent systematic review and meta-analysis did not directly address the effect of Diane 35 on triglyceride levels but highlighted the importance of considering lipid profiles in the management of polycystic ovary syndrome (PCOS), a condition for which Diane 35 is sometimes prescribed 1. Given the potential for increased triglyceride levels, careful consideration and monitoring are recommended when prescribing Diane 35, especially in patients with risk factors for hypertriglyceridemia or cardiovascular disease.

From the Research

Effects of Diane 35 on Triglyceride Levels

  • The study 2 found that significant increases in serum triglyceride were observed after the 3rd cycle of treatment with Diane 35.
  • Another study 3 also reported a substantial increase in triglycerides both in the serum and in the very low density lipoprotein (VLDL) fraction when cyproterone acetate was combined with ethinyl estradiol.
  • The study 4 found an increase in triglycerides at six and twelve months of treatment with cyproterone acetate combined with ethinyl estradiol.
  • However, the study 5 did not specifically report an increase in triglyceride levels with Diane 35 treatment, but rather found that it did not induce any change in the lipid profile compared to metformin.
  • The study 6 reported an improvement in lipid metabolism with the combination of Diane 35 and metformin, but did not specifically mention the effect on triglyceride levels.

Key Findings

  • Multiple studies have reported an increase in triglyceride levels with Diane 35 treatment 2, 3, 4.
  • The increase in triglyceride levels may be a concern for some patients, particularly those with pre-existing lipid metabolism disorders.
  • However, the studies also reported that the mean levels of triglycerides remained within the normal range throughout the treatment period 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Effects of a low-dose estrogen-antiandrogen combination (Diane-35) on lipid and carbohydrate metabolism in patients with polycystic ovary syndrome.

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 1990

Research

Effects of cyproterone acetate (CPA) on serum lipoproteins when administered alone and in combination with ethinyl estradiol (EE).

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 1987

Research

Metabolic effect at six and twelve months of cyproterone acetate (2 mg) combined with ethinyl estradiol (35 micrograms) in 31 patients.

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 1990

Research

Management of polycystic ovarian syndrome with Diane-35 or Diane-35 plus metformin.

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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