What medications improve volume loss and wrinkling in perimenopausal (perimenopause) women?

From the Guidelines

For perimenopausal women experiencing volume loss and wrinkling, hormone replacement therapy (HRT) with estrogen-containing formulations is the most effective medication option, as it can significantly improve skin thickness, hydration, and elasticity. According to the US Preventive Services Task Force recommendation statement 1, estrogen therapy can be used to treat symptoms of menopause, such as hot flashes or vaginal atrophy, and may also have benefits for skin health. Estrogen-containing formulations like Premarin (0.625mg daily) or estradiol patches (0.05mg twice weekly) can be considered, and these can be combined with progesterone (100-200mg daily) for women with an intact uterus to prevent endometrial hyperplasia.

Some key points to consider when prescribing HRT for perimenopausal women with volume loss and wrinkling include:

• The use of bioidentical hormones is not recommended due to lack of FDA approval and limited data on their safety and effectiveness 1
• The American Heart Association and the American Congress of Obstetricians and Gynecologists recommend against the use of menopausal hormone therapy for the primary or secondary prevention of cardiovascular disease 1
• A thorough medical evaluation is necessary to assess risks, particularly for women with a history of breast cancer, blood clots, or cardiovascular disease
• Topical retinoids such as tretinoin (0.025-0.1% cream applied nightly) can also be beneficial for reducing fine lines and improving collagen production
• Injectable dermal fillers containing hyaluronic acid (like Juvederm or Restylane) can restore lost volume, while neurotoxins (Botox, Dysport) can reduce dynamic wrinkles.

From the FDA Drug Label

The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. The Women’s Health Initiative (WHI) enrolled a total of 27,000 predominantly healthy postmenopausal women to assess the risks and benefits of either the use of oral 0.625 mg conjugated estrogens (CE) per day alone or the use of oral 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate (MPA) per day compared to placebo in the prevention of certain chronic diseases.

Estradiol may improve volume loss and wrinkling in perimenopausal women by:

• Replacing the decreased estrogen levels during menopause
• Acting on estrogen-responsive tissues
• However, the FDA drug label does not directly address the improvement of volume loss and wrinkling in perimenopausal women. The use of estrogen therapy should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman 2, 2, 2.

From the Research

Medications for Volume Loss and Wrinkling in Perimenopausal Women

• Hormone replacement therapy (HRT) is a commonly recommended treatment for managing menopausal symptoms, including volume loss and wrinkling 3, 4, 5, 6.
• HRT can help improve the symptoms of menopause, including vasomotor symptoms, mood disruption, and genitourinary symptoms 3, 5, 6.
• Estrogen-based hormonal therapies are the most effective treatments for many menopausal symptoms, including volume loss and wrinkling, and have a generally favorable benefit:risk ratio for women below age 60 and within 10 years of the onset of menopause 6.
• Non-hormonal treatment options are also available for managing perimenopausal and menopausal symptoms, although HRT is often the most effective treatment 6.

Considerations for HRT Use

• The use of HRT has been associated with potential risks, including an increased risk of cardiovascular disease and breast cancer 3, 4.
• However, more recent studies have suggested that these risks may be lower than previously thought, particularly for women who start HRT close to the onset of menopause 4, 5.
• Individualized decision making and a symptom-driven treatment approach can help improve health and quality of life for midlife women 6.