What are the treatment options for chronic anovulation?

Treatment Options for Chronic Anovulation

The most effective treatment for chronic anovulation depends on the underlying cause, with first-line options including lifestyle modifications for weight loss in obese patients, clomiphene citrate for ovulation induction in those desiring pregnancy, and combined hormonal contraception for menstrual regulation in those not seeking pregnancy. 1

Diagnostic Evaluation

Before initiating treatment, proper diagnosis is essential:

• Measure serum levels of LH, FSH, prolactin, progesterone, testosterone, and other hormones to identify the underlying cause 1
• Check for polycystic ovary syndrome (PCOS), which affects 4-6% of the general population and is a common cause of chronic anovulation 1
• Evaluate for functional hypothalamic amenorrhea (FHA), which is associated with stress, excessive exercise, and weight loss 1
• Screen for thyroid dysfunction, hyperprolactinemia, and other endocrine disorders that can cause anovulation 1
• Consider transvaginal ultrasound to assess for polycystic ovarian morphology 1

Treatment Options Based on Underlying Cause

For PCOS-Related Anovulation

1. Lifestyle Modifications:

   • Weight loss of as little as 5% can normalize menstrual cycles and restore ovulation 2
   • Regular exercise and dietary changes are first-line interventions 1

2. For Women Desiring Pregnancy:

   • Clomiphene citrate is the first-line medication for ovulation induction 3, 2
     • Indicated for women with adequate endogenous estrogen levels 3
     • Treatment should not exceed six cycles (including three ovulatory cycles) 3
   • Metformin can improve insulin sensitivity and ovulation rates 1
     • May result in ovulation in some premenopausal anovulatory women 4
     • Often used as an adjunct to clomiphene citrate 5
   • Gonadotropins are second-line therapy when clomiphene fails 6, 7
   • Laparoscopic ovarian drilling may be considered when medications fail 2

3. For Women Not Seeking Pregnancy:

   • Combined oral contraceptives are effective for regulating cycles and reducing androgen levels 1
   • Cyclic progestins (such as medroxyprogesterone acetate) can be used to prevent endometrial hyperplasia 1

For Functional Hypothalamic Amenorrhea

1. Address Underlying Causes:

   • Reduce excessive exercise, correct energy deficits, and manage psychological stress 1
   • Aim for BMI ≥18.5 kg/m² before ovulation induction 1

2. For Women Desiring Pregnancy:

   • Pulsatile GnRH therapy is more effective than exogenous gonadotropins 1
   • Clomiphene citrate is less effective in FHA and should only be considered in women with sufficient endogenous estrogen levels 1

3. For Women Not Seeking Pregnancy:

   • Hormone replacement therapy to prevent complications of hypoestrogenism 1

For Other Causes of Anovulation

• Hyperprolactinemia: Dopaminergic agents like cabergoline 6
• Thyroid dysfunction: Appropriate thyroid hormone replacement or suppression 1
• Endometrial protection: Women with chronic anovulation are at increased risk for endometrial hyperplasia and cancer and require cyclic progestin therapy or combined hormonal contraception 1, 8

Monitoring and Follow-up

• Monitor for ovulation using basal body temperature, mid-luteal progesterone levels, or ovulation predictor kits 3
• For women on clomiphene citrate, be aware of the 7.98% risk of multiple pregnancies 3
• Women with chronic anovulation should be monitored for endometrial hyperplasia, especially if they have prolonged unopposed estrogen exposure 8

Common Pitfalls and Caveats

• Failure to distinguish between PCOS and FHA can lead to inappropriate treatment choices 1
• Clomiphene citrate is contraindicated in women with ovarian cysts (except in PCOS), abnormal vaginal bleeding, or liver dysfunction 3
• Metformin may cause gastrointestinal side effects but has fewer side effects than thiazolidinediones 1, 5
• Untreated chronic anovulation increases the risk of endometrial hyperplasia and carcinoma, requiring appropriate surveillance 8
• In women with FHA who also have polycystic ovarian morphology (FHA-PCOM), diagnosis can be challenging and may require additional testing to differentiate from PCOS 1

Remember that treatment should be directed at both restoring ovulation (if pregnancy is desired) and preventing the long-term consequences of chronic anovulation, particularly endometrial hyperplasia and cancer 1, 8.