Current understanding on pharmacokinetics, clinical efficacy and safety of progestins for treating pain associated to endometriosis

ABSTRACT

Introduction: Endometriosis is a chronic estrogen and progestogen responsive inflammatory disease associated with pain symptoms and infertility. The medical therapy of endometriosis aims to induce decidualization within the hormonally dependent ectopic endometrium, and it is often administered to ameliorate women’ pain symptoms or to prevent post-surgical disease recurrence. A variety of progestins have been used in monotherapy for the medical management of women with endometriosis.

Areas covered: This review aims to offer the reader a complete overview of pharmacokinetic (PK) and clinical efficacy of progestins for the treatment of endometriosis.

Expert opinion: Each progestin has a distinct PK parameters and pharmacodynamics affinity not only for progesterone receptor, but also for other steroid receptors, such as estrogen, androgen, and glucocorticoid. Moreover, progestins can also be delivered in different formulations. All these characteristics influence their final biological effect. Randomized, controlled, non-blinded studies support the use of oral progestin-only treatment for pelvic pain associated with endometriosis. Currently, the only two progestins approved by Food and Drug Administration (FDA) for the treatment of endometriosis are norethindrone acetate (NETA) and depot medroxyprogesterone acetate (DMPA).

KEYWORDS:

• Endometriosis
• progestins
• medical therapy
• norethindrone
• dienogest
• depot medroxyprogesterone
• LNG-IUD

Article highlights

• Progestins have been increasingly and successfully employed as monotherapy for the treatment of endometriosis related pain symptoms, being efficacious and well tolerated in several randomized, controlled, non-blinded studies;

• Progestins have good a long-term tolerability profile. However, the main drug-related AEs are spotting and breakthrough bleeding, depression, breast tenderness and fluid retention;

• Currently only norethindrone acetate (NETA) and depot medroxyprogesterone acetate (DMPA) as monotherapy have been approved by the Food and Drug Administration (FDA) for the treatment of endometriosis;

• NETA is one of the most studied progestin for the treatment of endometriosis. Its good safety-profile and efficacy in improving endometriosis-related pain do NETA a suitable medical option among first-line therapies;

• One of the best long-term medical treatment for endometriosis is the LNG-IUD. In comparison with the systemic administration, its local release of progestin has similar or improved efficacy, particularly evident on the local target organ, with reduced systemic AEs.

• Further studies are needed to clarify the effect of long-term treatment with progestins on bone mineral density (BMD).

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.