Reimagining Menopause with Hormones and Longevity

In today’s era of personalized medicine and aesthetic optimization, we must shift our understanding of menopause from a biological inevitability to a modifiable longevity marker. The intersection of hormone science, aesthetics, and functional medicine is now central to how we manage the aging female patient. We can reframe the role of the ovary not simply as a reproductive organ but as a pivotal driver of female vitality, healthspan, and even epigenetic inheritance.

For clinicians working in aesthetic medicine, the implications are profound. Our patients’ skin, mood, weight, and perceived aging are tightly linked to their hormonal milieu. Estrogen, in particular, is not just a “beauty hormone” but a master regulator that impacts nearly every hallmark of aging.

THE OVARY AS AN ORGAN OF LONGEVITY

While the ovary is often viewed through the lens of fertility, its reach extends well beyond reproduction. The ovary is the first organ to age. By 20 weeks of gestation, a female fetus has 6 million to 7 million oocytes; at birth, that number drops to 1 million to 2 million, and by menarche, only about 300,000 remain. This relentless decline continues until menopause, when just 1,000 eggs are left.

This biological timeline has implications not just for fertility but also for lifespan. Women who experience late menopause (after age 53) live up to 7 years longer than those with early menopause. Even the brothers of these women enjoy increased longevity—pointing to genetic and epigenetic mechanisms linked to ovarian aging.

THE MASTER REGULATOR OF AGING

Estrogen, particularly estradiol, is profoundly geroprotective. It interacts with virtually every cellular system implicated in aging:

• Genomic stability: Estrogen promotes DNA repair and reduces genomic instability.
• Epigenetic regulation: It supports DNA methylation, preserving youth-associated gene expression.
• Mitochondrial function: Estrogen enhances mitochondrial biogenesis and function.
• Telomere preservation: Women have longer telomeres than men, until menopause.
• Immune regulation: Estrogen reduces chronic inflammation and supports immune resilience.

So powerful is estrogen’s influence that we may reconsider menopause not as a natural transition but as a modifiable trigger of systemic aging.

THE BRAIN–OVARY AXIS AND MENOPAUSAL SYMPTOMS

Menopause symptoms are brain-driven. The hypothalamus, which governs circadian rhythm, thermoregulation, libido, mood, and sleep, is the first to feel estrogen’s absence. This explains the widespread but individualized symptoms: hot flashes, cognitive fog, insomnia, mood swings, and low libido.

Estrogen’s loss impacts the skin, soft tissue, muscle, and metabolism. The aesthetic signs are familiar: sudden facial sagging, jowling, mid-body fat accumulation, and a decline in skin glow. I call this constellation the SAG sign—sudden aging in the context of gonadal decline.

RETHINKING HORMONE THERAPY

The Women’s Health Initiative (WHI) cast a long shadow over hormone therapy. As a young researcher, I questioned the exclusion of natural progesterone from the trial design. We now know that the WHI used the wrong hormones (synthetic), delivered the wrong way (oral), to the wrong population (older, asymptomatic women). The result was a generation of undertreated menopausal women.

Today, we must move beyond outdated language. I advocate for hormonal optimization therapy (HOT)—not “replacement” but personalized, data-driven, patient-led care. In my practice, this begins with the patient’s goals: “Do you want to be mentally sharp, sexually active, vibrant, and look the part?” From there, I customize therapy using bioidentical hormones, which are structurally and functionally identical to human hormones, though not necessarily custom-compounded. Delivery method matters: patches, creams, sublinguals, and vaginal inserts each have unique pharmacokinetics. The site of application also matters; facial skin, for instance, is rich in ER-β receptors, making it a compelling site for topical therapy.

Baseline screening is critical. Beyond symptom questionnaires or urine metabolites, I assess breast density, family history, and genetic risk to tailor a safe and effective regimen.

ESTROGEN AND SKIN

As aesthetic practitioners, we often encounter estrogen-deficient skin without recognizing it. Estradiol, while potent, carries systemic risks and may not be appropriate for cosmetic use. However, estriol—a weak estrogen with strong affinity for ER-β—offers several advantages:

• Topical safety: Less systemic absorption and non-proliferative on breast tissue
• Cosmetic potential: Improves dermal thickness, hydration, and glow
• End-metabolite status: Does not convert to more carcinogenic estrogen derivatives

Emerging research on “soft estrogens” (topical analogs metabolized fully in the skin) promises targeted estrogenic effects without systemic risk.

UNBOXING MHT: A CLINICAL UPDATE

In November 2025, the US Food and Drug Administration (FDA) announced intent to remove the long-standing boxed warning on menopausal hormone therapy (MHT)—an overdue correction to end the overgeneralized fear messaging that has persisted in the wake of the WHI trial.^1-5

This move is symbolic, signalling an end to the fearmongering and stigma that has limited the use of MHT, and this is particularly true for low-dose vaginal estrogen. As a result of the overrepresentation of risk and inappropriate extension of findings from the WHI trial, menopausal women have been undertreated, resulting in erosion of quality of life and increased risk of disease including complications of urinary tract infections associated with the genitourinary syndrome of menopause (GSM).

The FDA has clarified its plan to remove the broad box warning related to cardiovascular disease, breast cancer, and probable dementia for certain MHT products while retaining the endometrial cancer warning for systemic estrogen-only therapy in women with a uterus (clinically mitigated with the use of progesterone).

While the motion to remove the FDA box warning is widely regarded as long overdue and favorable, some public messaging by FDA Commissioner Mark Makary, MD, has been criticized for overstating claims about MHT reducing dementia risk or extending longevity, despite the absence of definitive randomized trial evidence.

ESTROGEN SIGNALING AND THE SKIN

Menopause produces an estrogen-deficient syndrome that dramatically affects the skin’s health, appearance, and aging. Estrogen-deficient skin loses 30% of its collagen within 5 years of menopause, and as the microarchitecture of the skin is altered, there is thinning, loss of hydration, impaired wound healing, inflammation, susceptibility to UV damage, and structural degradation.

Estrogen’s effects on skin are mediated through multiple signaling pathways, most notably estrogen receptor beta (ERβ), estrogen receptor alpha (ERα), and rapid non-genomic pathways including GPER1. In skin, ERβ is the key functional receptor, widely expressed in keratinocytes, fibroblasts, hair follicles, and the dermal microvasculature. This ER subtype is strongly linked to collagen production, barrier integrity, immunity, and wound healing—the determinants of youthful skin. By contrast, ERα plays a prominent role in reproductive function and is more proliferative.

With the dramatic loss of ovarian estrogen (estradiol) at menopause, there is a resulting decrease in ERβ signalling, as well as ERβ density and concentration on fibroblasts, which in turn diminishes the regenerative capacity of the skin and upregulates inflammatory pathways, causing inflammaging. Menopause-mindful aesthetic care, therefore, must focus on the preservation of ERβ signalling to support the skin’s firmness, elasticity, thickness, hydration, health, and repair capacity.

Effective treatments for estrogen-deficient skin should follow these principals: where appropriate, systemic hormone optimization therapy (beauty from within), topical estrogen supportive care (cosmetic estrogen analogues), and bioregenerative approaches including biostimulators and biologics to preserve the skin’s structural and functional resilience.

Whether it is from endogenous sources (eg, ovary, fat, skin) or exogenously applied (systemic or topical), estrogens are not all the same. Women throughout their reproductive lives have 3 predominant estrogens: estradiol (E2), estrone (E1), and a weak estrogen metabolite estriol (E3). Estradiol is the major ovarian estrogen and has high binding affinity for both ER subtypes. When applied to the skin, estradiol will have systemic effects; this is true for both the pharmaceutical and compounded forms. While estriol is a weaker estrogen and available only in the compounded form (in North America), it too will exert systemic effects on both forms of the ER when used cosmetically.

CRITIQUES OF COSMETIC ESTROGENS

While the off-label use of pharmaceutical estrogen products for cosmetic effect is on the rise and promoted widely on social media, this practice has drawn criticism and lacks clinical support. Some physicians and medical societies criticize the use of compounded hormones, citing lack of FDA oversight, uncertain systemic absorption, and the absence of a drug monograph. These critiques fail to distinguish the nuances of estrogen therapy, including differentiating between the forms of pharmaceutical estrogen (systemic vs vaginal), the type of hormone (estriol vs estradiol), and engineered estrogen analogues referred to as “soft estrogens” (which have been clinically investigated for cosmetic use and are FDA approved as non-hormone cosmetics due to lack of systemic effect).

Presently, the optimal skin-direct approach to address estrogen deficiency is to use estrogens designed for cosmetic use that bind both ERs with moderate affinity and are fully metabolized in the skin. While some SERMs and several investigational compounds show high affinity for Erβ, there are no currently available evidence-based ERβ exclusive therapies.  As we anticipate advancements in treating estrogen-deficient skin, forward-facing practitioners can embrace menopausal aesthetic paradigms combining estrogen cosmetics with bioregenerative therapies.

WEIGHT GAIN AND THE METABOLIC THEORY OF MENOPAUSE

Menopause is often accompanied by a 15-lb weight gain, primarily as visceral fat. This is not merely cosmetic; it is inflammatory, insulin-resistant fat, driving cardiovascular and metabolic risk. Estrogen therapy alone will not reverse this. What is needed is a comprehensive metabolic management approach that includes nutritional optimization; resistance training to preserve lean mass; targeted supplementation; and pharmacologic strategies where appropriate.

As we push menopause later in life and extend female healthspan, managing body composition and inflammation becomes a cornerstone of longevity.

DISRUPTING MENOPAUSE: THE FUTURE IS NOW

What if we could delay or even eliminate menopause? We now have the science to do so. I am collaborating with a reproductive longevity laboratory that is actively exploring ovarian tissue cryopreservation, not for fertility but for menopausal deferral. This strategy involves cryopreserving ovarian tissue from women in their 30s, reimplanting aliquots of tissue decades later in small quantities, and maintaining natural hormone production well beyond the natural menopausal window.

Coupled with AI-based assessment tools to determine optimal timing for intervention, this approach could shift menopause from an inevitability to an option.

The implications are staggering. Instead of managing symptoms, we may one day postpone ovarian senescence entirely, enabling women to enjoy decades more of hormonal vitality, with benefits for brain, bone, skin, and beyond.

A NEW ERA

We are at the dawn of a new era in women’s health, where aesthetics, longevity, and hormone science intersect. The ovary is no longer just the reproductive clock; it is a master regulator of aging. Menopause, as we currently define and manage it, is outdated.

Through hormonal optimization, aesthetic hormone therapy, and even ovarian preservation, we can empower women to live not just longer but better. As aesthetic providers, it is time we embrace our role in this mission, not merely as beautifiers but as partners in lifelong vitality. 

Editor’s note: This article is based on a presentation delivered at the 2025 Genesis: Innovations in Aesthetic Regenerative Medicine Meeting.

1. HHS Advances Women’s Health, Removes Misleading FDA Warnings on Horomone Replacement Therapy. US Food and Drug Administration website. https://www.fda.gov/news-events/press-announcements/hhs-advances-womens-health-removes-misleading-fda-warnings-hormone-replacement-therapy. Published November 10, 2025. Accessed January 12, 2026.

2. FACT SHEET: FDA Initiates Removal of “Black Box” Warnings From Menopausal Hormone Replacement Therapy Products. https://www.hhs.gov/press-room/fact-sheet-fda-initiates-removal-of-black-box-warnings-from-menopausal-hormone-replacement-therapy-products.html. US Department of Health and Human Services website. Published November 10, 2025. Accessed January 12, 2026. 

3. Makary MA, Nguyen CP, Høeg TB, Tidmarsh GF. Updated Labeling for Menopausal Hormone Therapy. JAMA. 2025 Nov 10. Epub ahead of print. 

4. The Menopause Society Comments on the FDA Announcement on Hormone Therapy. The Menopause Society website. https://menopause.org/press-releases/the-menopause-society-comments-on-the-fda-announcement-on-hormone-therapy. Published November 10, 2025. Accessed January 12, 2026.

5. ACOG President Says Label Change on Estrogen Will Increase Access to Hormone Therapy. American College of Obstetricians and Gynecologists website. https://www.acog.org/news/news-releases/2025/11/acog-president-says-label-change-on-estrogen-will-increase-access-to-hormone-therapy. Published November 10, 2025. Accessed January 12, 2026.