A Better Approach to GSM (Genitourinary Syndrome of Menopause)

Genitourinary Syndrome of Menopause (GSM) is one of the most common—and most under-treated—conditions affecting women in midlife and beyond. It is often dismissed as “just dryness,” but in reality, GSM represents a broader decline in the health and function of vaginal and vulvar tissues.

Common symptoms include:

• Vaginal dryness

• Burning or irritation

• Pain with intimacy (dyspareunia)

• Decreased lubrication

• Recurrent urinary tract infections

• Urinary urgency

• Reduced sexual sensation or arousal

• Clitoral and vulvar atrophy

These symptoms can significantly impact quality of life, relationships, and overall well-being.

Why Systemic Hormones Are Often Not Enough

Even in patients on systemic hormone replacement therapy (HRT), GSM may persist.

This is because:

• Circulating hormone levels do not always adequately restore local tissue health

• Vaginal and clitoral tissues require direct hormonal support for full restoration

For this reason, local vaginal hormone therapy should be considered standard of care for moderate to severe GSM.

A More Complete Treatment Approach: The “2–2–20” Formula

2-2-20 is a compounded vaginal hormone cream designed to restore both structure and function:

2–2–20 Formula

• Estradiol (E2): 2 mg/mL (0.2%)

• Testosterone: 2 mg/mL (0.2%)

• DHEA: 20 mg/mL (2%)

Why This Combination Works

Estradiol (E2)

• Restores vaginal epithelium

• Improves lubrication and elasticity

• Reverses atrophic changes

Testosterone

• Enhances sensitivity and sexual response

• Supports clitoral and vulvar tissue health

• Improves arousal and function

DHEA (Prasterone Precursor)

• Provides intracrine hormone conversion within vaginal tissue

• Converts locally into both estrogen and androgens

• Supports tissue regeneration and function

Clinical Insight

Estradiol alone is often effective for dryness.

However, many patients report:

“It’s better—but it still doesn’t feel the same.”

That difference is often due to:

• Androgen deficiency

• Loss of tissue responsiveness

• Reduced local hormone conversion

Combination therapy addresses all three.

How It Is Used

Typical dosing:

• Apply 0.5 mL (2 clicks):

  • External (vulva/clitoris)

  • At the vaginal opening (introitus)

  • Internally

• Nightly for 6–8 weeks, then

• 2–3 times weekly for maintenance

Expected Timeline

• Early improvement: 2–4 weeks

• Full tissue restoration: 2–3 months

Consistency is key.

When to Adjust

Increase if:

• Persistent dryness

• Pain with intimacy

• Poor tissue response

Decrease if:

• Excess discharge

• Local irritation

Safety of Vaginal Estradiol

Low-dose vaginal estradiol has been shown to:

• Produce minimal systemic absorption

• Maintain serum estradiol levels within postmenopausal range

• Be safe for most patients, including many with a history of breast cancer (in consultation with their oncologist)

This is a key distinction from systemic estrogen therapy.

Why Not Bi-Est?

Bi-Est (estradiol + estriol mixtures) is commonly marketed, but:

• Estradiol (E2) is the primary active estrogen needed for symptom relief

• Estriol (E3) is weaker and adds little clinical benefit in most cases

• Mixed formulations reduce precision and predictability

Using pure estradiol allows for more consistent and effective treatment.

The Goal: Restoration, Not Just Relief

The goal of GSM treatment is not simply to reduce symptoms—but to restore:

• Tissue integrity

• Function

• Sensation

• Comfort

With the right approach, many women experience a level of improvement they did not realize was possible.

Final Thought

If you have been told that these symptoms are simply part of aging—or that limited improvement is the best you can expect—it may be time to consider a more comprehensive approach.

Selected References

1. North American Menopause Society (NAMS).
   The 2020 genitourinary syndrome of menopause position statement.
   Menopause. 2020;27(9):976–992.

2. Faubion SS, Larkin LC, Stuenkel CA, et al.
   Management of genitourinary syndrome of menopause in women with or at high risk for breast cancer.
   Menopause. 2018;25(6):596–608.

3. Simon JA, Goldstein I, Kim NN, et al.
   The role of androgens in the treatment of genitourinary syndrome of menopause (GSM).
   Menopause. 2018;25(7):837–847.

4. Labrie F, Archer DF, Koltun W, et al.
   Efficacy of intravaginal DHEA (prasterone) for vaginal atrophy.
   Menopause. 2016;23(3):243–256.

5. Suckling J, Lethaby A, Kennedy R.
   Local estrogen therapy for vaginal atrophy in postmenopausal women.
   Cochrane Database Syst Rev. 2006;CD001500.