The menopause transition is a natural endocrine milestone characterised by a progressive decline in circulating estrogen, progesterone, and testosterone [1] . Given the skin’s dense expression of hormone receptors, this hormonal attenuation exerts profound effects on cutaneous physiology - [7] . Historically underexplored, the dermatological consequences of menopause are now receiving increasing scientific attention. As the skin is a hormonally responsive organ, shifts in endocrine activity during perimenopause and menopause have measurable impacts on structural and functional skin parameters - [11] . Estrogen, progesterone and androgens act on cutaneous receptors to modulate collagen synthesis, antioxidant defences, immune surveillance, and lipid barrier maintenance - . Disruptions to these systems during menopause can precipitate a cascade of adverse cutaneous outcomes, diminishing skin health and aesthetic appearance - . Targeted dermatologic intervention during this period may therefore play a crucial role in restoring homeostasis and preserving skin vitality.

Given the growing recognition of menopause as a critical window for targeted dermatologic care, this research aims to address an underexplored clinical need: research-based, non-invasive interventions designed to mitigate the cutaneous impacts of hormonal decline. By intervening at the level of topical therapy, this study investigates whether structured, topical skincare can re-establish physiological equilibrium within the skin, thereby supporting health, vitality, and visual rejuvenation throughout the menopause transition.

Reductions in skin sensitivity of 53%, 69% and 76.9% were self-reported by subjects ( Figure 1 ) and confirmed by investigator analysis at 30, 60 and 90 days post treatment. Similarly, reductions in cutaneous erythema were reported and confirmed at 30, 60 and 90 days of 69.2%, 84.6% and 69.2% post treatment.

Skin dehydration is a common dermatologic consequence of menopause. Alleviation of this condition of 78.57% was self-reported ( Figure 2 ) and confirmed by investigator analysis at 30, 60 and 90 days post treatment.

Related to dehydration but manifesting as easily irritated and tight, flaky skin is commonly reported in menopause. Improvements in skin dryness of 76.9% and 84.6% were self-reported ( Figure 3 ) and confirmed by investigator analysis at 30, 60 and 90 days post-treatment.

Loss of skin luminosity and an accompanying complexion dullness are commonly reported by perimenopausal, menopausal and post-menopausal women. Improvements in skin clarity and radiance of 36.3%, 63.6% and 90.9% were self-reported by subjects ( Figure 4 ) and confirmed by investigator analysis at 30, 60 and 90 days.

Wrinkles are defined as folds or creases in the skin, which are known to be associated with a decline in skin elasticity and are often considered to be a result of excessive sun exposure over time. The baseline results for this patient were 13% and increased to 57% over a 12-week period ( Figure 6 ).

Wrinkles are defined as folds or creases in the skin, which are known to be associated with a decline in skin elasticity and are often considered to be a result of excessive sun exposure over time. The baseline results for this patient were 9% and increased to 99% over a 12-week period ( Figure 7 ).

Red Areas were examined in this study to identify improvement in a variety of potential skin conditions that could be exacerbated by sun damage (inflammation, rosacea etc.). This patient experienced a 32% decrease in Red Spots ( Figure 7 ).

Tolerability and Adverse Events

Two participants (10%) experienced transient adverse responses:

Participant A exhibited mild cutaneous reactivity following four weeks of daily use of the prescribed skincare regimen. Clinical presentation included itching localised to the lower face and the emergence of small pustular lesions on the neck and décolletage. The adverse response was managed through the temporary cessation of active ingredients and simplification of the at-home regimen. Upon gradual reintroduction, both Niacinamide and Bakuchiol were successfully tolerated by Day 60.

Participant B experienced cutaneous sensitivity within two weeks of initiating the prescribed regimen. The subject presented with erythema, stinging sensations, and xerosis. These symptoms resolved following the temporary suspension of active ingredients and simplification of the at-home regimen. Successful reintroduction of Niacinamide was achieved by Day 60 in the form of #1 Crème, following an unsuccessful attempt with #1 The Serum, which resulted in a recurrence of sensitivity.

These outcomes underscore the necessity of individualised treatment planning for sensitive phenotypes.

Estrogen, plays a pivotal role in maintaining skin homeostasis by binding to specific estrogen receptors expressed in key cutaneous cells, including keratinocytes, fibroblasts, sebaceous glands, hair follicles, and immune cells such as Langerhans and macrophages - [6] - [14] . Upon binding to these receptors, estrogen activates or suppresses specific genes, regulating essential skin functions such as collagen production, lipid synthesis, inflammatory control, and the maintenance of epidermal barrier integrity - [15] . Notably, estrogen enhances the skin’s antioxidant capacity by upregulating the expression of antioxidant enzymes such as Superoxide Dismutase (SOD) Glutathione Peroxidase (GPx), thereby contributing to the reduction of oxidative stress [16] [17] .

During perimenopause and post-menopause, diminished estrogen levels disrupt these processes, manifesting as structural and functional alterations [2] [6] . Reduced fibroblast activity impairs collagen and elastin synthesis, causing dermal thinning, decreased elasticity, and wrinkle formation. . Attenuated sebaceous and lipid function compromises the epidermal barrier, promoting xerosis, rough texture, and increased transepidermal water loss . Dysregulated inflammatory signaling heightens cutaneous reactivity, while diminished antioxidant defenses exacerbate oxidative stress, leading to dullness and uneven tone . Concurrently, impaired estrogen-mediated modulation of Langerhans cells and macrophages compromises immune surveillance and reparative capacity [3] [13] .

Though discussed less frequently, progesterone and testosterone also influence skin physiology during peri-menopause and post-menopause. The natural decline in progesterone levels affects the brain’s chemical signalling systems—most notably the GABA system—which plays a key role in maintaining calmness and balance, as well as supporting emotional stability, focus, and sleep [19] . These functions are indirectly linked to skin health through elevated cortisol levels. Elevated cortisol is associated with impaired wound healing, increased collagen and elastin degradation, and amplified inflammatory processes [20] . Furthermore, sleep disruption has been clinically correlated with impaired skin barrier function, increased transepidermal water loss (TEWL), delayed cellular repair processes, and contributes to a dull, lackluster complexion [21] . Progesterone plays a modulatory role in cutaneous homeostasis, contributing to the regulation of inflammatory responses within the skin and influencing sebaceous gland activity to support balanced sebum production [1] [2] .

Testosterone, an androgen with known roles in collagen maintenance and structural support via musculoskeletal systems, influences cutaneous function by stimulating sebaceous gland activity [17] [22] [23] . During periods of hormonal fluctuation, the pro-inflammatory and pro-oxidative effects of androgens may become pronounced, often manifesting clinically as nodulocystic acne predominantly localised to the lower facial region [5] [24] .

The integration of a structured daily at-home regimen, comprising targeted solar protection and reparative interventions, in conjunction with adjunctive clinical therapies, demonstrated significant efficacy in supporting cutaneous health in estrogen-deficient skin - [29] . Clinical treatment regimens that were individually tailored according to cutaneous presentation, incorporated customised topical pharmacologic agents in combination with LED light therapy [26] [27] . This dual-modality approach yielded superior clinical outcomes, substantiating the role of combined photoprotective and reparative strategies with in-clinic treatments in mitigating menopausal skin changes - [30] . Among participants receiving professional in-clinic treatments, 70% reported measurable improvement in skin quality, accompanied by enhanced self-perception, self-esteem, and confidence.

Further knowledge, based on the reported adverse responses, confirmed the need for targeted and personalised skincare regimen, especially for sensitive skins. While two participants initially reacted mildly to Niacinamide and Bakuchiol specifically, their skins showed better tolerability by day 60. This was made possible by simplifiying their skincare regimen to remove the incriminated ingredients for a few weeks all the while building up their skin resilience and finally reintroducing gradually the ingredients.

The potent agents, although designed for the less resilient skins, can occasionally trigger reactions depending on the concentration and whether the skin it is applied to has an impaired skin barrier.

The documented improvements reflect the potency of the RATIONALE Essential Six in modulating skin inflammation, oxidative stress, and barrier function during hormonal decline [27] - [29] . The synergistic inclusion of antioxidants, bio-lipids, anti-inflammatory actives, barrier-repair agents, and photoprotective compounds is consistent with current mechanistic understanding of menopausal skin physiology.

The authors acknowledge the limitations of the study. Due to resources restrictions, the study group counted only twenty participants who had never been exposed to the skincare products chosen so that can represent their own controls. The products were presented and used in an open-label manner and was performed by the sponsors staff members, which assisted in understanding how to best tailor the skincare regimen based on the skin types and needs but also could be viewed as biased. Future research will further elucidate ingredient-specific contributions in a close-label manner and via an external lab as well as explore expanded treatment algorithms incorporating in-clinic interventions.

The findings of this 12-week study affirm the efficacy of the RATIONALE Essential Six regimen in restoring cutaneous health during the menopause transition. The combination of structured at-home application with adjunctive clinical therapies yielded superior outcomes, substantiating a dual-modality approach to optimising menopausal skin care.

The authors disclose that this study was entirely funded by RATIONALE Skincare Pty Ltd., Victoria, Australia.

Continued

Menopause and Skin Health Questionnaire

Continued

Continued