Can the progesterone-only pill (Progestin) be used to treat endometriosis?

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From the Guidelines

Yes, the progesterone-only pill (POP) can be used to treat endometriosis, as it has been shown to reduce the size of lesions and alleviate symptoms, according to the American College of Obstetricians and Gynecologists 1.

Treatment Options

The progesterone-only pill is a viable treatment option for endometriosis, particularly for patients who cannot take estrogen-containing contraceptives due to risk factors like migraines with aura, history of blood clots, or who are breastfeeding.

  • POPs like norethindrone acetate (Aygestin, 5-15 mg daily), dienogest (Visanne, 2 mg daily), or desogestrel (Cerazette, 75 mcg daily) are effective options.
  • Treatment is typically continuous without breaks to suppress menstruation and is often maintained long-term until pregnancy is desired or symptoms are adequately controlled.
  • POPs work by thinning the endometrial lining, reducing menstrual flow, and sometimes stopping periods altogether, which helps decrease the growth and activity of endometriosis lesions.
  • They also reduce inflammation associated with endometriosis.

Side Effects and Considerations

Side effects may include irregular bleeding, headaches, mood changes, and breast tenderness.

  • While POPs can effectively manage symptoms for many patients, they may not be as effective as combined hormonal contraceptives for some individuals, and response varies between patients.
  • A more recent study published in 2021 suggests that natural micronized progesterone may have a favorable profile in terms of minimizing hormonal-related cardiovascular risks and thrombotic risk 1.

Recommendation

Based on the most recent and highest quality study, the use of progesterone-only pill, specifically natural micronized progesterone, is recommended for the treatment of endometriosis, due to its effectiveness in reducing symptoms and minimizing cardiovascular risks 1.

From the Research

Treatment of Endometriosis with Progesterone Only Pill

  • The progesterone only pill can be used to treat endometriosis, as progestins are synthetic compounds that mimic the effects of progesterone and have been demonstrated to be effective in reducing or eliminating pain symptoms in approximately 90% of patients 2.
  • Progestins are available in many forms, including oral preparations, injections, subdermal implants, and intrauterine systems, and continuous progestin use is an effective therapy for the treatment of painful symptoms associated with endometriosis 2.
  • However, there is no evidence that progestin use is superior to other types of treatment in endometriosis-related pain symptoms 2.

Mechanism of Action

  • Progesterone resistance is a key factor for endometriosis sufferers, and medical therapy can avoid surgical intervention, which may lead to a reduced ovarian reserve, and its effects of earlier menopause and reduced fecundity 3.
  • Progesterone receptor isoform has provided new insight as the potential treatment, and progestin, anti-progestin, and selective progesterone receptor modulators usage, which target these receptors, could avoid hypo-estrogenic side effects, which can be debilitating 3.

Comparison with Other Treatments

  • Gonadotrophin-releasing hormone (GnRH) analogues, the levonorgestrel-releasing intrauterine system (LNG-IUD), and danazol were beneficial interventions for women with pain and endometriosis, and laparoscopic treatment of endometriosis and excision of endometriomata were also associated with improvements in pain 4, 5.
  • However, the evidence on the effectiveness of progestogens compared to other treatments is limited, and the quality of the evidence for specific comparisons ranged from very low to moderate 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Progestin therapy in endometriosis.

Women's health (London, England), 2015

Research

Reviewing the role of progesterone therapy in endometriosis.

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 2019

Research

Endometriosis: an overview of Cochrane Reviews.

The Cochrane database of systematic reviews, 2014

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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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