Local Estrogen Therapy for the Treatment of Vaginal Atrophy Figure 3: Vaginal Maturation Index35 A 100% B 100% * 80% 80% * 60% 60% ** * * * * * * *
40%
40%
20%
20%
0% Baseline 2 4 Weeks 8 12 (LOCF) Parabasal 52 (LOCF) Intermediate Superficial
A. Vaginal maturation index by cell type in the placebo treatment group; B. Vaginal maturation index by cell type in the 10 mcg 17β-estradiol treatment group. *p<0.001; 10 mcg estradiol versus placebo; **p=0.007; 10 mcg estradiol versus placebo. LOCF = last observation carried forward.
specific dose, and decreased leakage.27,34,36 In an atrophic vaginal
epithelium the estrogen cream and estradiol tablet can initially raise systemic estrogen by a small amount, until the epithelium thickens. According to where local estrogen is inserted in the vagina, there may be absorption variations. Absorption of estrogen to the uterus was significantly decreased when the tablet was inserted in the outer third of the vagina in a controlled crossover study of 10 post-menopausal patients assessing the site of insertion of 17β-estradiol tablets and endometrial safety.37
Systemic Estrogen Therapy
The risk for endometrial cancer related to systemic estrogen therapy is reduced by using a progestogen hormone.24
The
benefits of systemic administration include improvement of vasomotor symptoms and prevention of post-menopausal osteoporosis.40,41
Less
frequent administration and reduced doses can be used to lower the risk related to systemic hormone therapy.19,24,42,43
Among patients who
take systemic hormone therapy, it is estimated that 40 % nevertheless suffer persistent vaginal dryness.5
In view of this, and considering the
unwillingness of many patients to discuss vaginal symptoms, physicians should ask about persistent vaginal symptoms, as local estrogen therapy may be required to attain symptom control.24
Systemic Absorption of Vaginal Estrogen Therapy Estrogen Cream
Following 24 weeks of treatment at the maximum dose of CEE cream used, 1.25 mg/d, 21 of 59 (47%) patients had a serum estradiol level outside the post-menopausal range, >49 pg/ml.27
However, in another US OBSTETRICS & GYNECOLOGY
study involving 20 patients treated with CEE cream, 0.3 mg, there were no significant increases in serum estradiol and estrone levels after six months of therapy.44
In a study of estradiol vaginal cream in seven post-menopausal patients, 10 mcg daily for three weeks, followed by additional twice-weekly treatment for nine weeks, serum estrogen levels remained within the post-menopausal range during 12 weeks of use.28
The dose of vaginal
estradiol cream currently recommended by the manufacturer is 100 mcg one to three times a week after the initial daily dose.45
a non-placebo controlled study in only seven women therefore the effectiveness of the 10 mcg dose is undetermined.
43 This was
Systemic estrogen therapy is indicated for relief of VVA as well as many menopausal symptoms and can enhance women’s quality of life (see Figure 5).38,39
Figure 4: Vaginal pH Grade35
1.0 1.5 2.0 2.5 3.0
0.5 0.0 Baseline 2 4 Weeks Placebo 10 μg E2
Grade of vaginal atrophy: 0 = no, 1 = mild, 2 = moderate, 3 = severe. pH values assigned a grade: pH <5 = 0, pH 5–5.49 = 1, pH 5.5–6.49 = 2, pH >6.49 = 3. LOCF = last observation carried forward.
8 12 (LOCF) 52 (LOCF)
0% Baseline 2 4 Weeks 8 12 (LOCF) 52 (LOCF)
p<0.001 p<0.001 p<0.001 p<0.001
p<0.001
Mean vaginal pH grade
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