E3, 1st

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Estriol, Compounded Hormone Therapy, Vulvovaginal Atrophy, VVA,

There are three naturally occurring estrogens in the female body: estrone (E1), estradiol (E2), and estriol (E3). Of the three, estriol has the lowest estrogenic activity. In compounded hormone therapy, it is often combined with estradiol (E2) as part of a topical estrogen formulation (i.e., Bi-Est) used in the treatment of vasomotor menopausal symptoms like hot flashes and night sweats. However, for women whose menopausal symptoms are limited to vaginal discomfort, low-dose and even ultra-low dose estriol therapy are recommended as first line therapy.

Vulvovaginal atrophy (VVA), identified by symptoms such as vaginal dryness, dyspareunia (painful intercourse), vaginal discharge and discomfort, affect 20-45% of women at midlife and older. Unlike vasomotor symptoms that resolve with time, VVA can persist well past menopause affecting sexual relationships and ultimately a woman’s quality of life. Studies demonstrate that vaginal application of estriol at doses even as low as 0.05 mg can help women with their vaginal symptoms. In one study, authors evaluated the sexual function and quality of life of postmenopausal women treated with a vaginal gel containing 0.05 mg estriol. Women applied the gel daily for 3-weeks and then twice weekly for up to 12-weeks. Sixty-eight women were enrolled into the treatment group and results demonstrated a significant difference in terms of objective markers (e.g., assessment of vaginal atrophy, vaginal pH) as well as subjective symptoms (e.g., sexual health and quality of life). In contrast, the control group had no change from baseline measurements. Although limitations of the study include its small sample size and short-term follow-up, its results confirm previous research that shows that low doses of vaginal estrogens should be considered as an initial treatment option in menopausal patients presenting with vulvovaginal complaints.

Of note, guidelines for the treatment VVA recommend low-dose vaginal estrogen, including estriol, as first-line therapy for patients who have not responded to non-hormonal therapies such as lubricants and moisturizers.  The benefits of local therapy include greater efficacy as well as lower systemic exposure to estrogens.

Vaginal preparations containing conjugated estrogens and estradiol are available commercially in the US.  However, vaginal preparations containing estriol are only available through a compounding pharmacy.

 

References:

  1. Caruso S, Cianci S, Amore FF, et al. Quality of life and sexual function of naturally postmenopausal women on an ultralow-concentration estriol vaginal gel. Menopause 2015. [Epub ahead of print]
  2. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause 2013;20:888-902.
  3. de Villiers TJ, Gass ML, Haines CJ, et al. Global Consensus Statement on menopausal hormone therapy. Maturitas 2013;74(4):391-2.

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