Optimizing menopausal hormone therapy: For treatment and prevention, menstrual regulation, and reduction of possible risks Original paper

What was reviewed?

This review explains how menopausal hormone therapy and vaginal microbiome considerations shape modern care for peri- and postmenopausal symptoms, bleeding control, and long-term prevention. The article synthesizes evidence on estrogen and progestogen choices, timing of therapy, and routes of delivery. It highlights that all systemic estrogens relieve vasomotor and genitourinary symptoms to a similar degree, while the route and the paired progestogen drive differences in safety. The authors argue for transdermal estradiol to lower clot risk and for physiologic progesterone or dydrogesterone to limit breast effects. They also discuss estriol for local urogenital symptoms and note an estriol-plus-lactobacilli option that supports a healthy vaginal flora with very low systemic uptake. They frame sequential versus continuous combined regimens as tools to regulate bleeding and protect the endometrium, and they set the “window of opportunity” for starting therapy to enhance cardiometabolic benefit.

Who was reviewed?

The review focuses on symptomatic peri- and postmenopausal women, including those with high thrombotic or cardiovascular risk, and on younger women with premature ovarian insufficiency or surgical menopause who need longer replacement. It also considers women with intact uteri who require progestogen for endometrial protection and those who prefer local therapy for genitourinary syndrome of menopause. The discussion includes patients who need androgenic or antiandrogenic partial effects from chosen progestogens, and women who benefit from a levonorgestrel intrauterine device with transdermal estradiol when contraception and endometrial control matter.

Most important findings

The authors report that estrogen relieves symptoms across preparations, but delivery route changes risk. Transdermal estradiol can lower venous thromboembolism and stroke risk compared with oral forms, which supports it for women with clot or metabolic risk. The progestogen partner shapes breast outcomes; physiologic progesterone and dydrogesterone appear more breast-neutral than several synthetic agents and may lower risk signals seen in older trials that used medroxyprogesterone acetate. The paper links regimen choice to bleeding control: sequential regimens induce predictable withdrawal bleeding and suit perimenopause or early postmenopause, while continuous combined regimens aim for amenorrhea in established postmenopause. For endometrial protection, at least 10–14 days of a progestogen per cycle in sequential therapy, or daily progestogen in continuous therapy, remains essential.

Key implications

Clinicians can improve safety by starting therapy within the first 6–10 years after menopause and by favoring transdermal estradiol when thrombotic or metabolic risk is present. Pair estradiol with progesterone or dydrogesterone to maintain breast and vascular neutrality while protecting the endometrium. Use sequential regimens in the late reproductive transition and early postmenopause to manage bleeding, and move to continuous combined regimens for stable amenorrhea later. For genitourinary syndrome of menopause, consider estriol, and when suitable, use estriol with lactobacilli to support a lactobacillus-dominant vaginal microbiome at a very low estriol dose and with minimal systemic exposure. These points offer clear entries for a microbiome signatures database around lactobacillus-linked symptom relief and dose-sparing local therapy.