What is Osphena (ospemifene)?

Ospemifene (Osphena): A Selective Estrogen Receptor Modulator for Postmenopausal Dyspareunia

Ospemifene is an FDA-approved selective estrogen receptor modulator (SERM) specifically indicated for treating moderate to severe dyspareunia (painful intercourse) associated with vulvar and vaginal atrophy in postmenopausal women without a history of estrogen-dependent cancers. 1

Mechanism and Classification

Ospemifene belongs to the SERM class of medications, which have tissue-specific estrogenic agonist/antagonist effects. It has:

• Strong estrogenic effects on vaginal tissue
• Neutral to minimal effects on endometrial tissue
• Potential antiestrogenic effects on breast tissue
• Similar chemical structure to tamoxifen and toremifene 2

FDA-Approved Indication

Ospemifene is specifically approved for:

• Treatment of moderate to severe dyspareunia due to vulvovaginal atrophy in postmenopausal women
• First non-hormonal treatment approved for this indication 3

Efficacy

Clinical trials have demonstrated that ospemifene effectively:

• Improves vaginal epithelial cells (decreases parabasal cells, increases superficial cells)
• Normalizes vaginal pH
• Significantly reduces dyspareunia symptoms 4
• Improves overall female sexual function as measured by the Female Sexual Function Index (FSFI), with improvements in domains of:
  • Sexual pain
  • Arousal
  • Desire
  • Lubrication
  • Satisfaction
  • Orgasm 5

Safety Considerations

Important Contraindications

• Contraindicated in women with known or suspected breast cancer 1
• Contraindicated in women with a history of breast cancer 1
• Not recommended during pregnancy (may cause fetal harm)
• Not recommended during lactation
• Not recommended in severe hepatic or renal impairment 6

Common Adverse Effects (≥5%)

• Nausea, vomiting
• Somnolence, dizziness, insomnia
• Constipation
• Hyperhidrosis
• Fatigue
• Feeling cold
• Anorexia
• Headache
• Diarrhea 6

Clinical Application in Cancer Survivors

The NCCN guidelines provide specific recommendations regarding ospemifene use in cancer survivors:

• Recommended for dyspareunia in survivors of cancers that are not hormonally sensitive 1
• Not recommended for survivors with a history of estrogen-dependent cancers 1
• May be useful for survivors of other types of cancers 1

Treatment Algorithm for Postmenopausal Vulvovaginal Symptoms

For women with symptoms of vaginal/vulvar atrophy, the following stepwise approach is recommended:

1. First-line options:

   • Vaginal moisturizers for daily comfort
   • Lubricants for sexual activity
   • Vaginal gels, oils, topical vitamin D or E

2. Second-line options (if first-line fails or symptoms are severe):

   • Low-dose vaginal estrogen (for women without hormone-sensitive cancers)
   • Topical anesthetics (OTC or prescription)
   • Pelvic physical therapy

3. Third-line options:

   • Ospemifene (for women without history of estrogen-dependent cancers)
   • Vaginal dehydroepiandrosterone (DHEA/prasterone) (with caution in women on aromatase inhibitors) 1

Clinical Pearls and Pitfalls

• Ospemifene is the first and only non-estrogen treatment approved for dyspareunia associated with vulvovaginal atrophy 2
• Unlike vaginal estrogens, ospemifene has a unique tissue-selective profile that makes it suitable for vaginal symptoms while potentially having protective effects on breast tissue 7
• The safety of ospemifene has not been established in survivors of estrogen-dependent cancers - a thorough discussion of risks/benefits is essential 1
• Ospemifene has been shown to improve all domains of female sexual function, not just pain 5
• Ospemifene may have potential benefits for bone health, though it is not FDA-approved for osteoporosis prevention or treatment 7

Ospemifene represents an important non-hormonal treatment option for postmenopausal women suffering from dyspareunia, particularly those who cannot or prefer not to use estrogen-based therapies, provided they do not have a history of estrogen-dependent cancers.