Does long-term suppression with dienogest (a progestin) for endometriosis in a female patient of reproductive age cause a decrease in Anti-Müllerian Hormone (AMH) levels?

Does Long-Term Dienogest Suppress AMH Levels in Endometriosis?

Current evidence does not demonstrate that long-term dienogest treatment for endometriosis causes clinically significant decreases in AMH levels, as dienogest only moderately suppresses estradiol (maintaining levels around 28 pg/ml after 60 months) and lacks the profound ovarian suppression seen with GnRH agonists. 1, 2

Understanding the Mechanism

Dienogest differs fundamentally from GnRH agonists in its hormonal effects:

• Dienogest maintains moderate estradiol levels (approximately 28 ± 12 pg/ml after 60 months of continuous use), which is substantially higher than the profound hypoestrogenic state induced by GnRH agonists 2
• The drug exhibits only moderate antigonadotrophic effects rather than complete ovarian suppression, distinguishing it from agents that cause severe ovarian function impairment 1
• Dienogest demonstrates significantly fewer hypoestrogenic effects compared to GnRH agonists commonly used for endometriosis treatment 1

Evidence on Ovarian Reserve Markers

While the provided evidence does not directly measure AMH levels during dienogest treatment, the physiologic data strongly suggests preservation of ovarian function:

• AMH correlates with ovarian reserve and antral follicle count in reproductive-age women, and serves as an indirect marker of the primordial follicle pool 3
• AMH levels decrease with treatments causing profound ovarian suppression, particularly alkylating chemotherapy and high-dose radiotherapy that directly damage the ovarian reserve 3
• GnRH agonists may affect ovarian function, though meta-analyses show inconsistent results and limited long-term data on ovarian reserve preservation 3

Clinical Implications for Fertility Preservation

The moderate hormonal suppression profile of dienogest has important fertility implications:

• Long-term dienogest treatment (up to 65 months) maintains efficacy in reducing endometriosis-associated pelvic pain without evidence of progressive ovarian damage 2, 4
• Women desiring future fertility can use dienogest as a bridge therapy, as the drug's mechanism does not involve the severe ovarian suppression that would be expected to deplete ovarian reserve 5, 1
• Post-operative dienogest administration prevents endometrioma recurrence (1.5% recurrence rate) without documented adverse effects on ovarian function during follow-up periods averaging 30 months 6

Critical Distinction from GnRH Agonists

This is a crucial clinical differentiation:

• GnRH agonists create a "medical menopause" with profound estradiol suppression, while dienogest maintains physiologic estradiol levels sufficient to avoid severe hypoestrogenic effects 1
• The moderate antigonadotrophic activity of dienogest does not translate to the complete ovarian shutdown seen with GnRH agonist therapy 1
• Dienogest's safety profile over 60+ months without documented ovarian failure or premature menopause suggests preservation of ovarian reserve 2, 4

Monitoring Recommendations

For women of reproductive age on long-term dienogest:

• Baseline AMH measurement before initiating therapy can establish individual ovarian reserve status, particularly for women concerned about future fertility 3
• AMH testing during treatment is not routinely indicated unless there are clinical signs of ovarian dysfunction (amenorrhea persisting after discontinuation, symptoms of estrogen deficiency) 3
• Counseling should emphasize that dienogest is not contraception, as ovarian function is maintained and pregnancy can occur despite treatment 5

Important Caveats

• The absence of direct AMH measurement studies in the dienogest literature represents a knowledge gap, though the physiologic evidence strongly suggests ovarian reserve preservation 1, 2, 4
• Individual variation exists, and women with pre-existing diminished ovarian reserve (low baseline AMH) should receive counseling about age-related fertility decline independent of dienogest use 3
• Dienogest should be discontinued when attempting conception, as progestins are not appropriate during pregnancy attempts despite the lack of evidence for permanent ovarian damage 5