Hormonal Treatment Options for Endometriosis
Combined oral contraceptives (COCs) and progestins are the first-line hormonal treatments for endometriosis, with progestins such as norethindrone acetate, depot medroxyprogesterone acetate, and dienogest offering high efficacy with reduced side effects. 1
First-Line Hormonal Therapies
Combined Oral Contraceptives (COCs)
- Provide consistent hormonal suppression of endometriotic lesions
- Significantly protect against endometrial and ovarian cancers when used >3 years
- Extended or continuous cycles are preferred over traditional 21/7 day regimens
- Common side effects: irregular bleeding, headache, nausea (typically transient)
- Contraindications: severe uncontrolled hypertension, hepatic dysfunction, complicated valvular heart disease, migraines with aura, thromboembolism history 1
Progestins
- Highly effective for all endometriosis phenotypes
- Options include:
DMPA works by transforming proliferative endometrium into secretory endometrium and inhibits pituitary gonadotropin secretion, preventing follicular maturation and ovulation 2.
Second-Line Hormonal Therapies
GnRH Agonists
- Effective for pain relief (Level A evidence) when used for at least 3 months 1
- Requires add-back therapy (estrogen) to reduce bone mineral loss without reducing efficacy 1
- Add-back therapy can be introduced before the third month to prevent side effects 3
Other Second-Line Options
- Desogestrel progestin-only pills
- Etonogestrel implants 3
Third-Line Hormonal Therapies
- Aromatase inhibitors 4
Treatment Algorithm
Initial Assessment:
- Evaluate pain characteristics (dysmenorrhea, non-menstrual pelvic pain, dyspareunia)
- Assess fertility desires (hormonal treatments contraindicated if immediate pregnancy desired)
First-Line Treatment (for women not seeking immediate pregnancy):
- COCs (preferably in continuous regimen) OR
- Progestins (DMPA, dienogest, or LNG-IUS)
If First-Line Fails:
- Switch to another first-line option OR
- Escalate to GnRH agonists with add-back therapy
If Second-Line Fails:
- Consider aromatase inhibitors OR
- Surgical options (laparoscopic removal of lesions)
Post-Surgical Hormonal Treatment
- Hormonal treatment is recommended after surgical treatment to prevent pain recurrence and improve quality of life
- COCs or LNG-IUS are recommended as first-line post-surgical options
- COCs should be maintained long-term to prevent endometrioma recurrence if tolerance is good 3
- For dysmenorrhea, postoperative COCs should be used in a continuous scheme 3
Treatment Duration and Follow-up
- Long-term therapy is often necessary as symptoms frequently recur after treatment cessation
- Annual clinical review recommended for patients on long-term therapy
- Follow-up 1-3 months after starting COCs to assess efficacy and side effects 1
Important Considerations
- Approximately 11-19% of individuals with endometriosis have no pain reduction with hormonal medications 4
- 25-34% experience recurrent pelvic pain within 12 months of discontinuing hormonal treatment 4
- For women with endometriosis who required oophorectomy, combined estrogen/progestogen therapy can effectively treat vasomotor symptoms and may reduce disease reactivation 5
Pitfalls to Avoid
- Delaying treatment escalation when first-line therapies fail
- Using GnRH agonists without add-back therapy (increases risk of bone mineral loss)
- Discontinuing hormonal therapy too early (recurrence rates are high)
- Using progestins alone in women with endometriosis who have undergone oophorectomy (combined estrogen/progestogen therapy is more effective) 5
The most recent evidence supports a systematic approach to hormonal therapy for endometriosis, with COCs and progestins as first-line options, followed by GnRH agonists with add-back therapy if initial treatments fail 4, 1.