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Cited by 147Endometriosis Research and TreatmentEctopic Pregnancy Diagnosis and ManagementGynecological conditions and treatments

Progestogens for endometriosis: forward to the past

Open access
Vercellini, P.·2003·Human Reproduction Update
DOI 10.1093/humupd/dmg030
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Abstract

We performed a MEDLINE and EMBASE search to identify all studies published in the last decade in the English language literature on the use of progestogens for the treatment of endometriosis. Our aim was to clarify the biological rationale for treatment and define the drugs that can be used with their doses, routes of administration, efficacy and tolerability. Progestogens may prevent implantation and growth of regurgitated endometrium inhibiting expression of matrix metalloproteinases and angiogenesis, and they have several anti-inflammatory in-vitro and in-vivo effects that may reduce the inflammatory state generated by the metabolic activity of the ectopic endometrium, and the consequent immune response. Oral contraceptives increase the abnormally low apoptotic activity of the endometrium of women with endometriosis. Moreover, anovulation, decidualization, amenorrhoea and the establishment of a steady estrogen-progestogen milieu contribute to disease quiescence. Progestogens are effective in the control of pain symptoms in approximately three out of four women with endometriosis. Their effect does not seem to be inferior to that of other drugs used for the disease. Different compounds can be administered by the oral, intramuscular, subcutaneous, intravaginal or intrauterine route, each with specific advantages or disadvantages. Medical treatment plays a role in the therapeutic strategy when administered over a prolonged period of time. Given their good tolerability, minor metabolic effects and low cost, progestogens must therefore be considered drugs of choice and are currently the only safe and economic alternative to surgery. However, their contraceptive effectiveness limits their use to women who do not wish to have children in the short term.

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Crossref · 10.1093/humupd/dmg030

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  • Progestins offer long-term efficacy in endometriosis, but a number of these agents are associated with weight gain and androgenic effects when administered at the high doses required for efficacy.

    “Progestins offer long-term efficacy in endometriosis, but a number of these agents are associated with weight gain and androgenic effects when administered at the high doses required for efficacy”

    From Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial (2010) · cites this paper as Vercellini et al., 2003

    The Introduction and Conclusions say progestogens can be used long term and effectively control endometriosis pain. The Results report weight gain with some treatments and describe medroxyprogesterone acetate as having moderate androgenic activity. They do not establish that high doses are required for efficacy or link those adverse effects specifically to such doses. (LLM, conf=0.86)

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  • Depot medroxyprogesterone acetate has demonstrated efficacy equivalent to leuprolide acetate, but long-term use impacts adversely on bone mineral density, and the delay in resumption of ovulation that may follow discontinuation is a contraindication in women wishing to conceive in the near future.

    “Depot medroxyprogesterone acetate (MPA; 104 mg, subcutaneous injection, every 3 months) has demonstrated an efficacy equivalent to LA, but long-term use of depot MPA preparations is shown to impact adversely on bone mineral density (BMD), while the delay in resumption of ovulation that may follow discontinuation of this therapy is a contraindication to use in women wishing to conceive in the near”

    From Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial (2010) · cites this paper as Vercellini et al., 2003

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Irregular uterine bleeding is a known adverse effect of treatment with progestins, including depot preparations of MPA, which have been compared in trials against LA.

    “Irregular uterine bleeding is a known adverse effect of treatment with progestins, including depot preparations of MPA, which have been compared in trials against LA (Vercellini et al., 2003;Crosignani et al., 2006;Schlaff et al., 2006).”

    From Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial (2010) · cites this paper as Vercellini et al., 2003

    The intramuscular-route section identifies DMPA as a depot formulation of MPA and says uterine breakthrough bleeding may be prolonged and repeated. The paper describes a DMPA trial against an oral contraceptive plus danazol, but the passages do not support the claim that depot MPA was compared against LA. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Estrogen-progestins and progestins appear to be among the compounds that most favorably balance benefits, harms, and costs when hormonal treatments are continued for long periods.

    “Finally, when hormonal treatments are to be continued for long periods, estrogen-progestins and progestins appear to be among the compounds that most favorably balance benefits, harms, and costs (30,31).”

    From A stepped-care approach to symptomatic endometriosis management: A participatory research initiative (2018) · cites this paper as [30]

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Cites

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Research works printed but not linked: 2

  1. [22]22. Moore, J., Kennedy, S. and Prentice, A. (2003) Modern combined oral contraceptives for pain associated with endometriosis (Cochrane Review). In The Cochrane Library, Issue 1. Update Software, Oxford.
  2. [35]35. Prentice, A., Deary, A.J., Bland, E. (2003) Progestagens and anti-progestagens for pain associated with endometriosis (Cochrane Review). In The Cochrane Library, Issue 1. Update Software, Oxford.

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Authors
Vercellini, P.
Affiliations
University of Milan (IT)
Corresponding author
Vercellini, P.
ORCID
Vercellini, P.
Venue
Human Reproduction Update
Publisher
Oxford University Press (OUP)
Published
2003-07-01
Volume
9
Issue
4
Pages
387-396
ISSN
  • 1355-4786 (ISSN-L)
  • 1460-2369
DOI
10.1093/humupd/dmg030
OpenAlex
W2166974601
Cited by
147
References
51
Citations by year
2026: 2 · 2025: 2 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 1 · 2018: 11 · 2017: 3 · 2016: 4 · 2015: 8 · 2014: 9 · 2013: 8 · 2012: 12
FWCI
1.22
Type
journal article
Language
en
Open access
Locations
  • Human Reproduction Update (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
Keywords
progestogens, endometriosis, endometrial implantation, matrix metalloproteinases, angiogenesis, anti-inflammatory activity, endometrial apoptosis, oral contraceptives, anovulation, decidualization, pain management, route of administration, drug tolerability, alternative to surgery
MeSH terms
Endometriosis, Female, Humans, Pain, Progestins

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