The hormonal profile of norethindrone acetate: Rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis
Abstract
Gonadotropin-releasing hormone agonists (GnRHa) are an effective treatment of endometriosis-associated pelvic pain. The use of hormonal add-back therapy can alleviate the hypoestrogenic symptoms associated with GnRHa therapy, while preserving therapeutic efficacy. Norethindrone acetate (NETA) is a unique progestin that has both estrogenic and androgenic properties and is effective as an add-back regimen without estrogen supplementation. Through its estrogenic activity, NETA exerts beneficial effects on bone mineral density and vasomotor symptoms in women treated with GnRHa. In addition, NETA exhibits strong endometrial antiproliferative effects, which may result in further benefits for the endometriosis patient population. However, NETA add-back may be associated with progestogenic side effects and may lower high-density lipoprotein due to androgenic activity. These effects must be balanced with the overall benefits of NETA add-back therapy.
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NETA 5 mg/d was approved by the FDA as add-back therapy when combined with a GnRH agonist, based on RCTs in women with endometriosis.
“Based on results from RCTs in women with endometriosis, NETA (5 mg/d) was approved by the Food and Drug Administration (FDA) as add-back therapy when combined with a GnRH agonist [93].”
From Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review (2021) · cites this paper as [93]
NETA is partly metabolized to estrogens, with positive effects on bone metabolism.
“In addition, NETA is partly metabolized to estrogens [17,18], with subsequent positive effects on bone metabolism.”
From Oral and depot progestin therapy for endometriosis: towards a personalized medicine (2017) · cites this paper as [18]
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- Authors
- Chwalisz, K., Surrey, E., & Stanczyk, F. Z.
- Affiliations
- Colorado Center for Reproductive Medicine (US)
- University of Southern California (US)
- Venue
- Reproductive Sciences
- Published
- 2012-06
- Volume
- 19
- Issue
- 6
- Pages
- 563-571
- ISSN
- 1933-7191 (ISSN-L)
- 1933-7205
- OpenAlex
- W2067287778
- Cited by
- 58
- References
- 83
- Citations by year
- 2026: 7 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 9 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Reproductive Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- norethindrone acetate, add-back therapy, GnRH agonist, endometriosis, progestins, estrogenic activity, androgenic activity, estrogen deficiency, bone mineral density, vasomotor symptoms, HDL cholesterol
- MeSH terms
- Norethindrone Acetate, Endometriosis, Estrogens, Female, Humans, Gonadotropin-Releasing Hormone, Lipoproteins, HDL, Norethindrone, Osteoporosis, Progesterone, Bone Density, Pelvic Pain, Hot Flashes
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