Vaginal estrogens

Standard of care for symptomatic vulvovaginal atrophy.

Available in cream, ring and tablet forms and all relieve symptoms.

Vaginal preparations of estradiol can result in systemic absorption, but to a limited extent.

Levels of estradiol increased from a baseline level of 3 pg/mL to 17 pg/mL after 7 days of vaginal estradiol tablets and cojugated estrogen cream (Labrie F).

Estradiol levels decrease over time when intravaginal estrogens are used consistently.

Small, incremental increase and circulating estradiol occurs in women who use vaginal estrogen products.

Mean serum estradiol levels increase from approximately 11 pg per mill at baseline to 43 pg per mill after treatment.

The increase in serum estradiol levels is lower with vaginal estradiol inserts, tablets, and the 7.5 mcg/D estradiol ring compared with estrogen containing creams.

Increase in estradiol levels following vaginal estrogens do not reach levels seen in premenopausal women.

The clinical significance of this small increase in serum estradiol level induced by vaginal estrogen is not known.

No evidence that vaginal estrogen increases the risk of breast and endometrial cancer, coronary heart disease, stroke, or VTE.
No evidence of increased early breast cancer specific mortality in females with breast cancer in patients who use vaginal estrogen therapy compared with patients who did not use hormonal replacement therapy (McVickler).

Circulating estrogen levels Transient The Increased with the first application of vaginal estrogen on a trophic vaginal tissues.

Circulating estrogen levels transiently increase with the first application of vaginal estrogens on atrophic vaginal tissues.

Estrogen creams are the least expensive type of vaginal estrogens.

Management of urogenital atrophy in women with a history of breast cancer is best treated with low dose vaginal 17 B-estradiol vaginal estradiol tablets, 10  g or vaginal estradiol ring).

Vaginal estrogens are an effective treatment for urogenital atrophy, but safety is uncertain in patients with breast cancer due to potential systemic absorption.

Estradiol rings release 7.mcg/daily and vaginal estradiol 4 micrograms daily are associated with the leaset systemic absorption of estrogens.

Progesterone is not needed for endometrial protection with the administration of vaginal estrogens.

Vaginal testosterone cream has been shown to improve vaginal atrophy symptoms in postmenopausal women taking AIs.

In a controlled study persistent estradiol elevation was rare among patients with breast cancer on aromatase inhibitors using a vaginal ring or intravaginal testosterone, and the use of these products is reasonable in patients experiencing urogenital atrophy (Melisko M).

It is recommended capping the use of high-strength creams that contain estradiol 100 ?g/g (0.01%) at a single treatment period of no longer than 4 weeks: to lower the risk for adverse effects, such as blood clots, strokes, and certain types of cancer, which can result from absorption of estradiol into the bloodstream from intravaginal creams used to relieve vaginal atrophy symptoms in postmenopausal women.

Data indicated that in postmenopausal women who had used these creams, the levels of estradiol in the blood were higher than normal postmenopausal levels.

Randomized clinical trials of vaginal estrogen measuring endometrial stimulation was only 52 weeks long, so long-term endometrial safety of vaginally administered estrogen is not known: existing trials show no cases of endometrial cancer in published reports.

The Women’s Health Iniative study showed that there was no increased risk of cardiovascular disease and cancer in women using vaginal estrogens compared to women not using vaginal estrogen doing a median follow up of 7.2 years.

Despite the absence of evidence the vaginal estrogen increases the risk of breast cancer and endometrial cancer, coronary artery disease, stroke, and venous thromboembolism it carries the same box warning as a systemic hormone therapy.

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