Can a progesterone course cause ovarian cyst enlargement?

Progesterone's Effect on Ovarian Cyst Enlargement

Yes, progesterone treatment can cause ovarian cyst enlargement in some cases, particularly when used as add-back therapy with GnRH agonists or in certain hormonal conditions.

Mechanism of Progesterone's Effect on Ovarian Cysts

Progesterone's effect on ovarian cysts depends on several factors:

1. Type of cyst: Different cyst types respond differently to progesterone
2. Hormonal context: Whether progesterone is used alone or with other hormones
3. Underlying condition: Presence of conditions like PCOS or endometriosis

Evidence for Cyst Enlargement

The evidence indicates that progesterone can promote cyst growth through several mechanisms:

• When used as add-back therapy with GnRH agonists, progesterone has been observed to increase growth of existing cysts 1
• Progesterone add-back therapy in patients receiving GnRH results in increased growth of uterine leiomyomata, suggesting a similar growth-promoting effect may occur with ovarian cysts 1

Contraindications and Considerations

For women with existing ovarian cysts or polycystic liver disease (PLD):

• The KDIGO guidelines note that estrogen and possibly progesterone exposure may increase the risk of PLD progression 1
• Women with ADPKD and liver cysts should be educated about their contraceptive choices due to potential hormonal effects 1
• The impact of progestin-only methods (pills, injections, implants) on cyst growth is not fully established 1

Clinical Management Approach

Assessment of Ovarian Cysts

Before initiating progesterone therapy, evaluate:

1. Cyst characteristics: Size, morphology, and risk classification using O-RADS 2

   • Simple cysts ≤3 cm require no further management
   • Simple cysts >3 cm but <10 cm require follow-up ultrasound in 8-12 weeks
   • Nonsimple cysts require specialist evaluation regardless of size

2. Risk stratification:

   • O-RADS 1-2: Low risk (<1%)
   • O-RADS 3: Intermediate risk (1-<10%)
   • O-RADS 4-5: High risk (≥10%) 2

Monitoring During Progesterone Treatment

For patients on progesterone therapy with existing cysts:

• Perform baseline ultrasound before initiating therapy
• Schedule follow-up ultrasound in 8-12 weeks, preferably during the proliferative phase 2
• Monitor for symptoms of cyst complications (pain, rapid growth)
• Consider alternative contraceptive methods for women with significant cysts or PLD

Special Considerations

• Functional cysts: Research has shown that estrogen/progestin therapy does not improve the rate of disappearance of functional ovarian cysts 3
• Hormonal balance: In some veterinary studies, progesterone administration has been shown to reduce cyst lifespan in certain contexts, suggesting complex hormonal interactions 4, 5
• Underlying conditions: In rare cases like 17,20-lyase deficiency, elevated progesterone levels have been associated with giant ovarian cysts 6

Conclusion

When considering progesterone therapy in women with ovarian cysts, clinicians should:

1. Perform baseline imaging to document cyst characteristics
2. Consider alternative non-hormonal methods in women with significant or complex cysts
3. Monitor cyst size and morphology during treatment
4. Be aware that progesterone can promote cyst growth, particularly when used as add-back therapy with GnRH agonists

For women with PCOS or other conditions requiring hormonal management, the benefits of progesterone therapy must be weighed against the potential risk of cyst enlargement.