Navigating Menopause: Hormonal vs Non-Hormonal Therapies – ARC Summit
I wanted to discuss the pharmacological differences between oral and transdermal hormone delivery. Transdermal delivery requires a smaller total dose and is absorbed directly through the skin into the bloodstream, avoiding the liver’s first pass effect. It is typically applied once or twice a week, in contrast to oral delivery, which requires daily intake and undergoes liver metabolism, making it less convenient.
Over time, due to various studies and the modality of application, transdermal estrogens have gained popularity, including FDA-approved and some bioidentical estrogens that were only recently approved. For instance, Wiona by Indentical Hormones was recently FDA approved. This shift from oral estrogens to transdermal products has led to a rise in the popularity of compounded bioidentical estrogen products. However, medical societies have consistently advised against these products. Marketed as natural, they are synthesized in laboratories and remain unregulated, delivering inconsistent hormone levels. There’s evidence that bioidentical estrogen products can increase the risk of endometrial cancer due to often lacking a progesterone component.
Pharmaceutical-grade, FDA-approved bioidentical transdermal estrogen, such as EstroGel, is available. It’s crucial to note that transdermal estrogen is exclusively estradiol, whereas oral preparations, like conjugated estrogens (CE), are a mix of estrogens dominated by estrone sulfate and equilin sulfate with minimal estradiol content. Oral preparations, such as esterified estrogens and estradiol, differ in their metabolic conversion compared to CE, resulting in a variety of estrogen receptor affinities and activities.
Oral and transdermal estrogens are approved for menopausal use, including transdermal, oral, and vaginal products, though some have been discontinued. The general contraindications for both oral and transdermal estrogen include a known or suspected history of breast cancer or other estrogen-sensitive cancers, active deep vein thrombosis or pulmonary embolism, history of blood clotting disorders (e.g., Factor V Leiden), arteriothrombotic diseases, chronic liver diseases, and migraines with aura. These contraindications do not necessarily apply to transvaginal estrogen therapy, as its serum concentrations are extremely low.
The North American Menopause Society recommends that the black box warning applied to conventional systemic HRT not apply to transvaginal estrogen treatment. Current understanding is that hormonal therapy formulations, routes of administration, and timing of initiation produce different effects, with the timing of initiation being crucial, especially for those with premature menopause. Healthy women have a low absolute risk for HT, but it can increase the risk of thrombosis, stroke, and cardiovascular events. Initiating treatment in older women carries greater risks, and breast cancer risk increases with treatment beyond three to five years. Estrogen therapy may be considered for longer durations if the uterus is absent, as it carries a lower risk for breast cancer.
Before initiating therapy, it’s essential to consider each woman’s priorities and risk factors. Alternatives to hormone therapy include non-hormonal prescription drugs such as antidepressants, anticonvulsants, antihypertensives, and neuropathic pain medications, and a new non-hormonal medication approved for hot flashes called Qlaira. Additionally, lifestyle adjustments such as using fans, relaxation techniques, maintaining a cool environment, and a healthy diet can help manage symptoms. Alternative medicines also offer options, though they carry their own risks.
