Skin Never Builds Retinoid Resistance, Dermatologist Dray Says

Dr Dray

Topical retinoids continue binding cellular receptors indefinitely, meaning breakthrough acne or visible plateaus stem from hormonal shifts, poor compliance, or barrier irritation rather than drug tolerance.

AI-assisted summary of Does Your Skin Get Used to Retinol? The Truth About Skincare “Resistance” — original source. Check the original for full context.

Source published: 2026-09-18

Key ideas

The skin does not develop biological resistance to topical retinoids; acclimation simply marks the end of the initial retinization period where receptor-saturating side effects like peeling and dryness subside while cellular gene expression continues. (0:00)
Apparent treatment failures are frequently caused by internal physiological shifts—such as hormonal surges, perimenopause, or stopping oral contraceptives—which can overpower a previously sufficient topical maintenance regimen. (3:41)
Clinical evidence indicates that photoaging benefits achieved after one year of daily retinoid use can often be sustained on a reduced weekly schedule, whereas acne management requires uninterrupted, consistent application. (5:16)
Prescription retinoids like tretinoin, adapalene, tazarotene, and trifarotene demonstrate essentially equivalent long-term disease control, rendering arbitrary molecule switching or aggressive percentage jumps unnecessary and prone to barrier irritation. (9:37)

Detailed notes

## Background Published on YouTube by board-certified dermatologist Dr Dray on September 18, 2026, this video investigates whether skin can develop a biological 'resistance' to skincare actives, focusing on topical retinoids such as tretinoin and adapalene. The description outlines how the guide clarifies the distinction between skin tolerance and true drug resistance, while examining why acne may re-emerge during long-term maintenance therapy and why plateaus should not be mistaken for treatment failure.

## TL;DR Dr Dray dispels the popular myth that skin becomes immune or resistant to topical retinoids, explaining that the end of flaking and irritation simply signals skin barrier acclimation rather than reduced cellular efficacy. Retinoids continue binding to nuclear receptors and modulating gene expression indefinitely, meaning resurfacing breakouts or ongoing aging are usually driven by hormonal surges, natural chronological processes, or declining application adherence. Furthermore, rotating between different retinoid molecules or arbitrarily escalating potency rarely enhances disease control and often provokes counterproductive barrier disruption. Instead of piling on harsh exfoliants when results plateau, patients are advised to audit their prescription refill consistency, assess systemic lifestyle triggers, and consult a dermatologist.

## Atmosphere & style The presentation is analytical, pragmatic, and reassuring, delivered in Dr Dray's signature straightforward, evidence-based dermatological style. It cuts through social media skincare folklore and consumer marketing panic, replacing the frustration of perceived product failure with calm, anatomical explanations. Watching feels like an informative clinical consultation that systematically eases anxiety, steering viewers away from over-treating their skin and encouraging patience and disciplined maintenance.

## Bulletin - [00:00](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=0s) The skin does not develop biological resistance to topical retinoids; acclimation simply marks the end of the initial retinization period where receptor-saturating side effects like peeling and dryness subside while cellular gene expression continues. - [03:41](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=221s) Apparent treatment failures are frequently caused by internal physiological shifts—such as hormonal surges, perimenopause, or stopping oral contraceptives—which can overpower a previously sufficient topical maintenance regimen. - [05:16](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=316s) Clinical evidence indicates that photoaging benefits achieved after one year of daily retinoid use can often be sustained on a reduced weekly schedule, whereas acne management requires uninterrupted, consistent application. - [09:37](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=577s) Prescription retinoids like tretinoin, adapalene, tazarotene, and trifarotene demonstrate essentially equivalent long-term disease control, rendering arbitrary molecule switching or aggressive percentage jumps unnecessary and prone to barrier irritation.

## Key takeaways - [00:00](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=0s) Fading side effects such as redness, peeling, and flaking reflect skin tolerance and barrier stabilization after the retinization phase, not a loss of drug efficacy. - [02:10](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=130s) Topical retinoids operate by binding nuclear receptors to alter gene expression, normalize follicular cell shedding, lower inflammation, and stimulate collagen synthesis without cellular downregulation. - [03:41](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=221s) Acne recurrence and ongoing skin aging occur because acne is a fluctuating inflammatory disease and chronological aging continues, not because retinoids lose biological potency. - [03:41](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=221s) Retinoids serve as ongoing symptom managers and cell normalizers rather than permanent cures for chronic genetic conditions. - [05:16](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=316s) Adherence drift is a primary hidden cause of returning breakouts, as patients frequently reduce treatment frequency after the initial weeks of therapy. - [05:16](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=316s) Photoaging improvements can often be sustained on a lower weekly frequency after one year of daily retinoid use, whereas acne control requires continuous regular application to stop microcomedone formation. - [06:38](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=398s) Environmental changes—such as relocating to an arid climate or increased urban pollution exposure—can stress the skin barrier and alter treatment response. - [06:38](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=398s) Declining estrogen levels during perimenopause and menopause drive dermal collagen and elasticity loss that topical retinoids alone cannot counteract. - [07:54](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=474s) Reacting to acne flares by layering leave-on exfoliating acids or applying extra retinoid damages the skin barrier and induces secondary inflammation that worsens breakouts. - [07:54](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=474s) Discontinuing oral contraceptives often triggers aggressive acne rebound because topical retinoids lack systemic androgen-suppressing capabilities. - [09:37](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=577s) Other active skincare ingredients, including antioxidants and chemical exfoliants, maintain consistent biological pathways over time rather than inducing skin resistance. - [09:37](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=577s) There is no biological reason to cycle or switch between retinoid formulations to maintain results, as long-term disease control remains comparable across tretinoin, tazarotene, trifarotene, and adapalene. - [09:37](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=577s) Escalating retinoid concentrations rarely improves long-term control and frequently introduces avoidable cutaneous irritation and barrier impairment. - [11:51](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=711s) A therapeutic plateau represents an expected maintenance baseline rather than drug resistance, and minor dips in skin clarity do not indicate treatment failure. - [11:51](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=711s) Tracking prescription refill dates provides an objective compliance audit to confirm whether actual application frequency has dropped below therapeutic thresholds. - [11:51](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=711s) Breakthrough lesions may represent diagnostic mimicry or secondary overlapping dermatologic conditions rather than retinoid-resistant acne vulgaris. - [13:20](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=800s) Consulting a dermatologist via telemedicine or in-office visits allows early intervention and regimen adjustments before persistent skin instability leads to scarring.

## Detailed walkthrough ### [00:00](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=0s) Does Skin Build Resistance? Tolerance vs. Retinization

A common dilemma in dermatology and skincare is the sudden apparent failure of a long-trusted product. Many people use an active ingredient for months or even years with stellar results—breakouts stay under control, fine lines smooth out, and texture improves—only for breakouts or wrinkles to suddenly resurface. The immediate, intuitive conclusion is that the skin somehow "got used to" the product or developed a resistance to it. However, this interpretation conflates two completely different concepts: developing a biological tolerance to the therapeutic benefits of a drug versus the skin acclimating to its adverse side effects.

When beginning a topical retinoid, the skin typically undergoes an initial adjustment period known as retinization. During this phase, the active ingredient is essentially "getting dumped in there, overwhelming the receptors," resulting in telltale dryness, peeling, flaking, and heightened sensitivity. Over time, as the skin acclimates, the barrier stabilizes and these irritating side effects subside. Crucially, a lack of ongoing peeling and stinging does not mean the ingredient has stopped working. Acclimation simply means the retinization period is over; the molecule is still penetrating the skin, binding to cellular receptors, and carrying out its intended biological duties.

[02:10](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=130s) The Cellular Biology of Topical Retinoids

To understand why a retinoid cannot simply lose its punch through skin resistance, one has to examine its biological mechanism of action. Topical retinoids—spanning prescription formulations like tretinoin, tazarotene, trifarotene, and adapalene, as well as cosmetic over-the-counter options like retinol and retinaldehyde—operate by binding to specific nuclear receptors within skin cells. This binding directly alters cellular gene expression, effectively instructing skin cells on how to behave.

In acne management, retinoids normalize epidermal turnover and the maturation of cells lining the follicular pore, ensuring that dead keratinocytes shed properly rather than clumping together to form microcomedones and clogged pores. Simultaneously, they interact with inflammatory cells within the immune system to dampen cutaneous inflammation. In the deeper dermal layers, retinoids stimulate fibroblasts to synthesize new collagen, which softens fine lines and improves structural firmness. As Dr. Dray emphasizes, "the biology that makes the retinoid useful doesn't go away." Skin cells do not downregulate or deactivate these receptors to ignore the retinoid over time; the cellular machinery remains fully responsive throughout continued use.

```mermaid flowchart TD accTitle: Topical Retinoid Cellular Mechanisms accDescr: Flowchart illustrating how topical retinoids bind nuclear receptors to drive gene expression and regulate acne, inflammation, and collagen.

subgraph Reception["Receptor Level"] A["Topical Retinoids (Tretinoin, Adapalene, etc.)"] --> B["Nuclear Retinoid Receptors"] B --> C["Modulation of Gene Expression"] end

subgraph Action["Target Cell Responses"] C --> D["Epidermal Cells (Normalize turnover & pore shedding)"] C --> E["Immune Cells (Reduce cutaneous inflammation)"] C --> F["Dermal Fibroblasts (Stimulate collagen synthesis)"] end

subgraph Outcomes["Clinical Results"] D --> G["Unclogged Pores"] E --> H["Calmed Breakouts"] F --> I["Softened Fine Lines"] end ```

[03:41](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=221s) Why Acne Returns and Aging Continues Despite Retinoid Use

If the skin never becomes biologically resistant to retinoids, why do so many people experience sudden breakouts or new wrinkles after years of success? The reality is that the underlying drivers of both acne and skin aging are dynamic and continually evolving. Acne is a chronic, fluctuating inflammatory condition heavily driven by hormones. Hormonal surges or shifts can easily overpower a maintenance regimen that previously kept milder breakouts in check. A skincare routine that successfully manages acne today, tomorrow, and three months from now is not an absolute guarantee of lifelong clearance if internal physiology changes three years later.

Similarly, when it comes to anti-aging, topical retinoids are powerful, but they cannot stop the clock. While they promote modest collagen production, diminish dyspigmentation, and soften superficial wrinkles, they do not render skin immune to natural biological aging. Lifestyle factors, cumulative UV exposure, chronological degradation, and intrinsic aging processes march on regardless of how dedicated one is to skincare and sun protection. Patients reach a baseline plateau of improvement where results are maintained, but new age-related structural changes will inevitably accumulate over decades.

- **Dynamic Hormonal Drive:** Shifts in internal hormones can trigger new waves of acne that exceed what topical retinoid monotherapy can suppress. - **Aging Reality Check:** Retinoids optimize cellular function and repair existing damage, but they cannot entirely halt the biological mechanisms of human aging. - **Maintenance vs. Cure:** A retinoid manages symptoms and normalizes behavior while applied; it does not permanently alter genetics or cure chronic skin conditions.

[05:16](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=316s) Compliance Drift and Maintenance Regimens

Another major factor behind recurring breakouts is a subtle decline in patient compliance. Decades of clinical adherence research reveal a consistent pattern: patients are exceptionally diligent during the first week of a new regimen, particularly when prescribed only a single topical product. As soon as routines become complex or multiple prescriptions are introduced, compliance drops sharply. Over time, even the most enthusiastic skincare users subconsciously "slack," skipping applications here and there until they are underutilizing the active ingredient and losing disease control.

There is, however, an interesting nuance when using retinoids solely for photoaging versus acne. Clinical evidence suggests that after approximately one full year of consistent daily retinoid application, the anti-aging benefits achieved can often be maintained on a reduced, less frequent weekly schedule. In contrast, acne maintenance typically requires ongoing, consistent use to prevent follicular hyperkeratinization from recurring.

[06:38](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=398s) Environmental Triggers, Hormonal Shifts, and Menopause

A perceived loss of retinoid efficacy is frequently traceable to changes in lifestyle, surroundings, or systemic health. Environmental shifts can place new stresses on the skin that a standard routine cannot handle alone: - Moving to an arid climate that accelerates trans-epidermal water loss. - Adopting a walking commute that spikes direct exposure to wind, sun, and urban airborne pollutants. - Incorporating incompatible, irritating cosmetic products that compromise the stratum corneum.

Hormonal milestones represent another major inflection point, most notably the transition into perimenopause and menopause. As systemic estrogen levels decline, the loss of estrogenic signaling leads to a marked drop in dermal collagen synthesis and skin elasticity. Topical retinoids alone cannot replace systemic estrogen or overcome the biological consequences of estrogen depletion on the dermis. While retinoids continue to perform their specific functions, the accelerated loss of structural support during menopause will often reveal deeper wrinkling and skin thinning regardless of retinoid use.

[07:54](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=474s) When Barrier Irritation Worsens Acne (and the Impact of Stopping Meds)

When acne flares up during retinoid treatment, a common instinct is to double down—applying the retinoid more aggressively or layering leave-on exfoliating acids like AHAs and BHAs. This approach almost always backfires. Piling on harsh actives overtaxes the moisture barrier, creating profound irritation and secondary inflammation that exacerbates the very breakouts the user is trying to eliminate. Instead of self-treating by destabilizing the skin barrier, flaring acne warrants an evaluation by a board-certified dermatologist.

Systemic medication changes also frequently unmask acne that was previously suppressed by multi-modal therapy. A classic scenario involves a patient using both an oral contraceptive pill and a topical retinoid: - Oral contraceptives regulate systemic androgen activity and suppress sebum production. - Topical retinoids normalize pore turnover and calm local inflammation. - When the birth control pill is discontinued, systemic hormonal regulation disappears.

Because topical retinoids exert zero systemic hormonal control, inflammatory acne often rebounds aggressively after birth control is stopped. Rather than waiting for breakouts to return and falsely blaming the retinoid, Dr. Dray advises patients to consult their dermatologist before discontinuing medications so alternative therapies can be initiated in advance. Furthermore, if excessive irritation arises during retinoid use, simple barrier-supportive adjustments—such as introducing a richer moisturizer or cutting face washing from twice a day to once daily—are far more effective than adding more active treatments.

[09:37](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=577s) Skincare Ingredients and the Myth of Switching Retinoids

The skin does not develop a tolerance to the biological mechanisms of other skincare ingredients either. Whether discussing antioxidant serums or exfoliating acids, these actives operate through the same biochemical pathways day in and day out. What actually changes over time is the underlying state of your skin or the external environmental conditions it is subjected to. This raises the common question: do you ever actually need to switch up your skincare products, particularly when it comes to topical retinoids? The short answer is no. There is no biological need to trade one retinoid for another simply "to keep things spicy and keep your skin on the edge of its seat."

The only practical reason to swap retinoid formulations is if you develop contact irritation or a sensitivity to a specific vehicle or inactive ingredient, in which case a dermatologist might transition you to an alternative formula. Otherwise, patients tend to vastly overestimate the comparative strength and real-world potency differences between various prescription options. The overarching clinical evidence demonstrates that across the board—whether evaluating tretinoin, tazarotene, trifarotene, or adapalene—long-term control remains essentially equivalent as long as the medication is tolerated and applied consistently. The primary objective is finding a formula your skin can sustainably tolerate rather than constantly chasing something new. Changing products or jumping to higher percentages often yields no additional therapeutic control and instead introduces unnecessary irritation. While a higher concentration might occasionally deliver more drug upfront to manage particularly thick, stubborn acne lesions faster, individual response variations do not mean a medication's biological efficacy fades over time.

- **Universal biological mechanisms:** Actives like antioxidant serums and chemical exfoliants continue performing their biological functions regardless of how long they have been used; ingredient failure is almost always attributable to shifts in skin barrier status or ambient climate. - **Retinoid equivalence:** With consistent adherence and good tolerability, tretinoin, adapalene, tazarotene, and trifarotene achieve comparable disease control over the long haul. - **The risk of escalating potency:** Arbitrarily stepping up percentages or switching molecules rarely enhances results and frequently provokes barrier disruption and dermatologic irritation.

[11:51](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=711s) Don't Confuse a Plateau with Resistance: Troubleshooting Flare-Ups

A critical rule in dermatologic care is: "Don't confuse a plateau with resistance." Reaching a maintenance phase where your skin stops making dramatic leaps in visible improvement—or even experiences a minor dip—does not signal that the active ingredient has suddenly ceased working. Often, managing chronic skin conditions simply requires adding a complementary agent, tweaking another component of the daily routine, or waiting out a natural fluctuation. When skin issues like acne flare back up, rather than assuming drug resistance, one must systematically investigate the underlying variables driving the recurrence.

```mermaid flowchart TD accTitle: Troubleshooting Recurrent Breakouts accDescr: Flowchart outlining the questions to ask when skin issues return during retinoid therapy. A["Acne or Eruption Returns"] --> B{"Audit Treatment Adherence"} B -->|"Refill delayed"| C["Inconsistent Application / Reduced Frequency"] B -->|"Refilled on time"| D{"Evaluate Systemic & Pattern Shifts"} D -->|"Internal changes"| E["Hormonal Shifts or New Medications"] D -->|"Location shifts"| F["Anatomical Pattern Changes (e.g., Jawline or Body)"] D -->|"Atypical lesions"| G["Misdiagnosis / Secondary Condition (Not true acne)"] ```

The first and most objective metric to audit is true adherence. Patients frequently believe they are using a medication faithfully when their actual habits have slipped. A foolproof accountability check for prescription topicals is looking at your pharmacy refill history: if a tube that should last a couple of months has stretched out over a far longer period, you are simply not applying it with the necessary frequency to sustain disease control. Beyond compliance, consider internal shifts such as new medications or hormonal changes, as well as shifts in eruption patterns—such as facial acne clearing up while new lesions emerge along the jawline or migrate to the trunk. Furthermore, self-diagnosis frequently leads patients astray because "not everything that looks like acne is acne." Conditions mimicking acne can emerge, just as patients managing atopic dermatitis (eczema) can develop secondary, overlapping skin conditions that masquerade as worsening primary disease when an entirely separate pathological process is at play.

- **Refill tracking as an adherence check:** Checking prescription renewal dates reveals whether treatment frequency has quietly tapered off below therapeutic levels. - **Pattern and systemic changes:** Re-emerging flares frequently correlate with hormonal fluctuations, systemic medication updates, or transitions from generalized facial acne to targeted jawline or body distributions. - **Diagnostic mimicry:** Breakthrough bumps may represent an entirely different dermatologic condition rather than a failure of the retinoid to manage acne vulgaris.

[13:20](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=800s) The Bottom Line and When to Consult a Dermatologist

The core takeaway is clear: skincare ingredients do not simply stop working, and your skin does not become biologically immune to their effects. When a routine appears to stall or backslide, chasing alternative formulations of the same active is rarely the answer. Pinpointing why your skin is responding differently requires looking at the broader clinical picture, and the most reliable way to navigate that assessment is by consulting your dermatologist—particularly when managing chronic skin diseases with prescription topicals.

Patients should not wait until their skin is severely flared or in crisis before seeking professional guidance. Reaching out at the first signs of persistent instability allows for timely regimen adjustments before significant damage or scarring occurs. Modern access makes this significantly easier: with the widespread availability of telemedicine, resolving a skincare plateau or flare does not always require fighting for an elusive in-office appointment window. Dermatologists can frequently accommodate patients through digital visits, evaluate the skin via high-resolution photos or video, and adjust treatment plans efficiently.

In closing, viewers experiencing plateauing results are encouraged to investigate systemic triggers rather than abandoning effective therapies. Dr Dray points viewers toward her related video on applying topical retinoids to the neck and signs off with her customary channel reminder to wear sunscreen and subscribe.

## Notable quotes > [00:00](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=0s) getting dumped in there, overwhelming the receptors — Dr Dray

> [02:10](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=130s) the biology that makes the retinoid useful doesn't go away. — Dr Dray

> [02:10](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=130s) Skin cells do not downregulate or deactivate these receptors to ignore the retinoid over time; the cellular machinery remains fully responsive throughout continued use. — Dr Dray

> [03:41](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=221s) A skincare routine that successfully manages acne today, tomorrow, and three months from now is not an absolute guarantee of lifelong clearance if internal physiology changes three years later. — Dr Dray

> [06:38](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=398s) Topical retinoids alone cannot replace systemic estrogen or overcome the biological consequences of estrogen depletion on the dermis. — Dr Dray

> [09:37](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=577s) to keep things spicy and keep your skin on the edge of its seat. — Dr Dray

> [09:37](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=577s) The primary objective is finding a formula your skin can sustainably tolerate rather than constantly chasing something new. — Dr Dray

> [11:51](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=711s) Don't confuse a plateau with resistance. — Dr Dray

> [11:51](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=711s) not everything that looks like acne is acne. — Dr Dray

> [13:20](https://www.youtube.com/watch?v=NEhoD-6m4BY&t=800s) Skincare ingredients do not simply stop working, and your skin does not become biologically immune to their effects. — Dr Dray

## Mentioned Dr Dray, Tretinoin, Adapalene, Tazarotene, Trifarotene, Retinol, Retinaldehyde, Can You Use Retinoids on the Neck?

## Video description Does your skin really get “used to” skincare ingredients? In this video, dermatologist Dr. Dray explains the difference between skin tolerance and true resistance, with a focus on topical retinoids like tretinoin, adapalene, tazarotene, and trifarotene.

Many people wonder why a skincare ingredient that once worked so well seems less effective over time, especially when acne starts coming back after years of successful retinoid use. Dr. Dray explains why this does not necessarily mean the skin has become resistant to the ingredient, and why topical retinoids can continue to be effective as long-term acne maintenance treatments.

The video covers why acne can return while using tretinoin, how changes in hormones, treatment consistency, irritation, skincare routines, and acne patterns can affect results, and why a plateau in visible improvement is not necessarily the same as treatment failure.

Dr. Dray also discusses whether people need to switch retinoids, how to recognize when irritation is being mistaken for worsening acne, and why “my skin got used to it” is often an overly simplistic explanation for changes in skincare results.

CHAPTERS:

0:00 Does your skin get used to skincare ingredients? 0:41 Your skin can become more tolerant 2:10 What topical retinoids actually do 3:41 Why acne can come back 5:16 Are you getting the same exposure to your retinoid? 6:38 When irritation complicates acne 9:30 Can your skin get used to other skincare ingredients? 9:56 Do you ever need to switch retinoids? 11:54 Don't confuse a plateau with resistance 12:08 What to ask when acne returns 13:20 The bottom line: tolerance vs. resistance

RELATED VIDEO: Can You Use Retinoids on the Neck? https://youtu.be/Z9W1W3X4BZA

Dr. Dray is a board-certified dermatologist who discusses evidence-based skincare, acne, retinoids, anti-aging skincare, and common skincare myths.

#Retinoids #Tretinoin #Skincare #Acne #Dermatologist #Retinol #Adapalene #AntiAgingSkincare #AcneTreatment #SkincareMyths

FTC: This video is not sponsored. Links are commissionable, meaning I may earn commission from purchases made through links.

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Disclaimer: This video is not intended to provide diagnosis, treatment or medical advice. Content provided on this Youtube channel is for informational purposes only. Please consult with a physician or other healthcare professional regarding any medical or health related diagnosis or treatment options. Information on this Youtube channel should not be considered as a substitute for advice from a healthcare professional. The statements made about specific products throughout this video are not to diagnose, treat, cure or prevent disease.

[Source](https://www.youtube.com/watch?v=NEhoD-6m4BY)

中文简报

Dray表示皮肤不会对维A酸类产生抗药性痤疮爆发主要由激素驱动外用维A酸类药物可无限期维持细胞受体活性，这意味着痤疮复发源于激素波动、用药依从性下降或屏障刺激，而非药物耐药。 Dr Dray 澄清了一个常见误区，即皮肤不会随着时间推移对局部外用维A酸类及其他护肤成分产生生物学抗药性或免疫。当初期刺激消退后，维A酸类药物仍会继续调节细胞代谢周期、基因表达和胶原蛋白合成，因此副作用的缓解仅代表皮肤适应，并不意味着药效丧失。突破性痤疮爆发或持续衰老通常是由体内激素激增、用药依从性下降、过度去角质导致的屏障受损，或超出单一外用疗法效果的内在生理衰老所驱动。对于痤疮再次复发的患者，与其轮换产品或盲目提高维A酸浓度，不如反思用药的规律性，保护皮肤屏障，并寻求针对性的皮肤科专业指导。使用维A酸类药物期间脱皮、干燥和刺激感的消退，表明皮肤屏障已逐渐适应，并不代表生物学疗效丧失或受体产生抗药性。 (0:41) 外用维A酸受体不会随时间发生下调；表面上的治疗失效通常是由于患者用药依从性下降、激素激增或屏障刺激所致。 (2:10) 痤疮维持治疗需要持续、规律地使用，而抗衰老维A酸疗法在每日使用约一年后，通常可以逐步减少为每周数次的低频维持方案。 (5:16) 为防止耐药而在不同外用维A酸类之间轮换在临床上没有必要，因为 tretinoin、adapalene、tazarotene 和 trifarotene 等处方制剂均可提供相当的长期疾病控制效果。 (9:56)

Reading summary

Dr. Dray explains that skin does not develop biological resistance or tolerance to topical retinoids or other active skincare ingredients. Apparent declines in effectiveness typically stem from barrier acclimation, hormonal fluctuations, declining patient compliance, or ongoing chronological aging rather than cellular desensitization. Barrier Acclimation Versus Drug Resistance (0:00) A widespread misconception occurs when the initial dryness, flaking, and irritation of retinoid use—known as retinization—subside. Users often assume that the absence of peeling means the product has stopped working or that the skin has grown resistant. In reality, Dr. Dray emphasizes that reduced irritation merely indicates that the skin barrier has acclimated and stabilized. At the cellular level, topical retinoids—including prescription agents like tretinoin and adapalene, as well as cosmetic retinol—operate by binding to specific nuclear receptors to alter gene expression. They normalize epidermal cell turnover, calm cutaneous inflammation, and stimulate collagen synthesis in dermal fibroblasts. Skin cells do not downregulate or deactivate these receptors over time; the biological pathways remain fully responsive with ongoing use. Dynamic Hormonal Shifts and Natural Aging (3:41) When acne flares or fine lines deepen after years of successful retinoid use, evolving internal physiology is typically the cause. Acne is a chronic inflammatory condition driven by hormones, and internal hormonal surges can easily overpower a topical maintenance routine that previously maintained clear skin. Similarly, major milestones such as perimenopause and menopause bring sharp drops in systemic estrogen, triggering accelerated collagen loss and skin thinning that topical retinoids alone cannot counterbalance. Furthermore, retinoids manage symptoms and optimize cellular function, but they cannot halt intrinsic human aging. While consistent use repairs superficial damage and modestly boosts collagen, cumulative UV exposure and natural chronological degradation inevitably continue. Improvement reaches a maintenance plateau, but this reflects biological realities rather than drug resistance. Compliance Declines and Barrier Overuse Pitfalls (5:16) Perceived loss of efficacy frequently traces back to adherence drift. Decades of clinical research show that patients naturally become less consistent over time, subconsciously skipping applications until they fall below therapeutic levels. Dr. Dray recommends checking pharmacy refill dates to verify whether a prescription meant to last two months has been stretched out significantly longer. While photoaging benefits can often be maintained on a reduced weekly schedule after a full year of daily use, acne control generally requires sustained, consistent application to prevent microcomedones from reforming. When breakouts do resurface, doubling down on retinoids or layering exfoliating acids like AHAs and BHAs backfires by stripping the moisture barrier. This induces secondary inflammation that worsens breakouts. Systemic changes also unmask acne; for example, stopping oral contraceptives eliminates systemic androgen suppression, causing acne to rebound aggressively despite continued topical retinoid application. Equivalent Efficacy Across Retinoid Formulations (9:37) There is no biological need to rotate skincare actives or switch retinoids simply to prevent the skin from adapting. Clinical evidence indicates that prescription retinoids—including tretinoin, tazarotene, trifarotene, and adapalene—provide comparable long-term disease control when applied consistently and tolerated well. Patients often overestimate potency differences between formulations. Changing products is only indicated if a user develops contact dermatitis to an inactive vehicle ingredient. Arbitrarily switching formulations or jumping to higher concentrations rarely provides superior long-term disease management and frequently provokes unnecessary barrier disruption. Dr. Dray concludes that addressing a skincare plateau requires evaluating treatment adherence, environmental stresses, hormonal changes, and possible diagnostic mimicry rather than abandoning effective actives. When routines stall, consulting a board-certified dermatologist—in-office or via telemedicine—enables appropriate regimen adjustments before scarring or severe irritation develops.

Source quotes

[0:00] Dr Dray: getting dumped in there, overwhelming the receptors [2:10] Dr Dray: the biology that makes the retinoid useful doesn't go away. [2:10] Dr Dray: Skin cells do not downregulate or deactivate these receptors to ignore the retinoid over time; the cellular machinery remains fully responsive throughout continued use. [3:41] Dr Dray: A skincare routine that successfully manages acne today, tomorrow, and three months from now is not an absolute guarantee of lifelong clearance if internal physiology changes three years later. [6:38] Dr Dray: Topical retinoids alone cannot replace systemic estrogen or overcome the biological consequences of estrogen depletion on the dermis. [9:37] Dr Dray: to keep things spicy and keep your skin on the edge of its seat. [9:37] Dr Dray: The primary objective is finding a formula your skin can sustainably tolerate rather than constantly chasing something new. [11:51] Dr Dray: Don't confuse a plateau with resistance. [11:51] Dr Dray: not everything that looks like acne is acne. [13:20] Dr Dray: Skincare ingredients do not simply stop working, and your skin does not become biologically immune to their effects.

Original transcript

[0:00] Well, hey guys. Welcome back. If you're [0:01] new here, I'm Dr. Dray. I'm a [0:03] board-certified dermatologist. Have you [0:05] ever found yourself having used a [0:08] particular skin care product, skin care [0:10] ingredient for many months, maybe even [0:13] many years, and then all of the sudden [0:15] the benefits that you were getting from [0:18] that ingredient or product or what you [0:19] had observed as being a positive no [0:22] longer seems to be holding up. For [0:24] example, maybe this was helping to [0:25] control breakouts and now you're [0:27] breaking out again. Maybe it was helping [0:29] to [0:30] diminish fine lines and wrinkles, but [0:32] now they're suddenly appearing. Does [0:34] that mean that the skin got used to [0:36] those ingredients? Did they stop [0:38] working? We're going to get into it in [0:40] today's video. First of all, let's clear [0:42] something up. When people talk about can [0:44] your skin become tolerant to an [0:46] ingredient, generally what they're [0:48] talking about and what I'm addressing [0:50] here is can your skin develop a [0:52] tolerance to the effect of an ingredient [0:56] as far as what you are pursuing, meaning [0:58] the drug or the active ingredient no [1:01] longer exerts the biological effect that [1:03] it should. For the purposes of today's [1:05] video, however, what it doesn't mean and [1:07] what you shouldn't confuse it with is [1:09] when your skin gets used to an [1:12] ingredient's adverse side effects. [1:14] Classic example of this is going to be a [1:16] topical retinoid. We all know that the [1:18] skin goes through this adjustment period [1:21] of what's referred to as retinization, [1:23] [clears throat] where the active [1:25] ingredient is kind of getting dumped in [1:27] there, overwhelming the receptors, and [1:29] you get a lot of dryness, peeling, and [1:31] heightened sensitivity. And with ongoing [1:33] use, that normalizes and those side [1:36] effects in most cases should subside. [1:39] However, it does not mean that over time [1:42] the skin starts to respond less well to [1:46] the topical retinoid. In other words, [1:48] lack of ongoing irritation, sensitivity, [1:50] dryness, and peeling from your topical [1:52] retinoid doesn't mean that the active [1:54] ingredient, the retinoid, is no longer [1:56] working. It just means that your skin [1:58] has acclimated, the retinization process [2:01] is over, and it's no longer excessively [2:03] irritating, but it's still able to get [2:05] in and bind to the receptors and exert [2:07] effects at the level of the skin cells. [2:10] To understand, however, why some people [2:12] might find that their retinoid stops [2:15] working, it's important to revisit what [2:16] exactly topical retinoids are intended [2:19] to achieve. Topical retinoids, which [2:21] include tretinoin, tazarotene, [2:22] trifarotene, adapalene, as well as the [2:25] cosmetic versions, retinol and [2:26] retinaldehyde, ultimately are designed [2:29] to bind to receptors in the skin and [2:31] exert their effects at the level of [2:34] cellular gene expression, meaning how [2:36] that cell behaves. For acne, for [2:39] example, they help to normalize the rate [2:41] at which skin cells turn over, such that [2:45] now you have smoother and more [2:47] predictable and more normal, if you [2:50] will, maturation of the epidermis lining [2:52] the pore, ultimately cutting down on [2:55] pore clogging. They also exert their [2:57] effects in this way on certain [2:59] inflammatory cells of the immune system [3:01] to help with reducing inflammation. And [3:04] within the deeper layers of the skin, [3:06] they exert these effects on the [3:08] fibroblasts, ultimately helping them to [3:10] produce more collagen, contributing to [3:12] how it is they work to reverse the [3:14] visible signs of skin aging, namely fine [3:17] lines and wrinkles. So, this is one of [3:19] the key reasons why topical retinoids [3:21] remain a cornerstone of treating acne [3:23] and are also utilized to improve the [3:26] visible signs of skin aging, as well as [3:28] many other indications. The biology that [3:31] makes the retinoid useful doesn't go [3:33] away, the skin cells don't down regulate [3:36] expression of those receptors so that [3:38] they start ignoring the topical [3:39] retinoid, nothing of that sort. So, then [3:42] why exactly is it that I used a topical [3:45] retinoid for years and then all of the [3:46] sudden my acne came back or I'm starting [3:49] to see dark spots, I'm starting to see [3:52] little fine wrinkles. Well, here's the [3:54] thing. The overall extent and severity [3:57] of acne can change a lot throughout your [3:59] lifetime. It's heavily influenced by [4:01] hormones. So, changes in your hormones [4:05] can lead to more breakouts that now are [4:08] no longer adequately going to be [4:09] controlled by a topical retinoid alone [4:12] or whatever prior regimen you were [4:14] using. Just because your medication [4:17] regimen gives good control of your acne [4:19] today, tomorrow, and 3 months from now [4:22] doesn't mean that 3 years from now it [4:24] can't still come back. Likewise, when it [4:27] comes to the visible signs of skin aging [4:30] and the improvements that you get with a [4:31] topical retinoid, remember, they improve [4:34] the appearance of, they modestly improve [4:36] collagen production, they can diminish [4:39] the appearance of little fine lines, [4:41] they can help to clear up unwanted [4:43] pigmentation, but they somehow do not [4:45] render your skin completely devoid of [4:48] the aging processes that contribute to [4:51] skin aging. In other words, just using a [4:53] topical retinoid and good skin care and [4:55] protecting your skin from the sun and [4:57] leading a healthy lifestyle, it's not [5:00] like it completely stops the aging [5:02] process. Nothing does that. It's just [5:04] the nature of how we exist, okay? So, [5:07] you're still going to accumulate [5:08] age-related change, in other words, and [5:10] you're going to observe that above and [5:12] beyond the improvements. You know, you [5:14] get to a level of improvement and that [5:16] is maintained. Here's another reason why [5:18] the acne might come back. Is that you [5:20] have to be honest with yourself. Are you [5:22] actually using the topical retinoid? [5:24] Because here's the thing that we have [5:26] come to learn over many years of people [5:29] studying how patients use their topical [5:32] medications. Most often, patients are [5:34] really good about using them regularly [5:37] in the first week. Provided you've only [5:39] given them one prescription, they don't [5:41] have to use multiple prescriptions. The [5:43] more prescriptions you give them, that [5:45] compliance decreases even further. [5:48] Suffice it to say, over time, no matter [5:51] how gung-ho you are, people tend to [5:53] slack. They may not even realize it. [5:55] They may start skipping nights here and [5:57] there, and then, depending on what it is [5:59] you're dealing with, like acne for [6:01] example, you might just be [6:03] underutilizing the ingredient, and [6:05] you're no longer exerting the level of [6:07] control that you need. Now, there's some [6:08] nuance here, because when we're talking [6:10] about the benefits that one gets as far [6:13] as anti-aging from a topical retinoid, [6:15] for example, there is some evidence that [6:17] suggests that once you go from using it [6:20] for about a year on a daily basis, well, [6:23] the benefits that you have obtained can [6:26] be maintained with a less frequent [6:28] weekly regimen. So, in other words, it [6:31] is possible to come down in the [6:33] frequency of use and maintain the [6:35] effects, the benefits, without [6:37] aggravating anything. Another [6:38] possibility is that something in your [6:40] routine or your lifestyle has changed. [6:42] Maybe you have introduced other [6:44] ingredients that increase irritation, [6:46] and that irritation is a contributing [6:48] factor to flaring the underlying skin [6:50] condition that private previously was [6:52] well controlled with just the topical [6:55] active ingredient that you're now [6:56] worried is no longer working. Hormonal [6:58] shifts, for example, can be a big [7:00] driving factor for nuance that worsening [7:03] acne. Also, environmental changes. Maybe [7:05] you moved, you live in a drier climate [7:07] now, you have to commute by foot, so you [7:09] have a lot more outdoor exposures. Maybe [7:11] you now live in a big city, and you have [7:13] a lot more pollution. These are all [7:15] contributing factors to skin problems, [7:17] and why all of a sudden now your topical [7:20] may no longer work. Not to mention [7:22] age-related changes, such as those that [7:24] occur around menopause with a decline in [7:26] estrogen, and you're going to get more [7:28] wrinkles. Topical retinoids are unlikely [7:30] to move the dial even further on the [7:34] estrogen depletion, if you will, that [7:36] happens in collagen. That's still going [7:38] to happen. You're still going to lose [7:40] that signal, and retinoids, they only do [7:42] so much. So, you're going to start [7:44] seeing that many case in many cases [7:47] women will with menopause. And if you're [7:49] curious, what about using a topical [7:50] estrogen? Check out my video on topical [7:52] estrogens for this very purpose. [7:54] Irritation can really complicate things. [7:56] Sometimes people think that if their [7:59] skin is breaking out more, well, maybe [8:01] they should be using their retinoid even [8:02] more frequently. Maybe they should try [8:04] different ingredients to get the [8:06] breakouts to come under control. They [8:08] add a bunch of exfoliating acids. The [8:10] next thing they know, they've actually [8:12] just taxed their skin barrier, caused a [8:14] lot of irritation that further [8:15] aggravates the underlying skin problem. [8:17] In other words, if you experience a [8:20] return of your disease process in the [8:23] case of acne, or you notice some [8:25] changes, don't try and get in there and [8:27] fix it yourself. See your dermatologist [8:29] to find out what's going on. Other [8:31] prescription medications might be needed [8:33] at this point to bring in that [8:34] additional piece of control. For [8:36] example, if you are someone who [8:39] previously was taking birth control [8:41] pills, and you also have been using a [8:43] topical retinoid. Well, say you need to [8:45] stop those birth control pills. Well, [8:48] once you do, you no longer have that [8:50] hormonal control from the birth control [8:52] pills, because topical retinoids don't [8:54] exert that hormonal control. And so, you [8:57] might experience a return of acne, and [9:00] you don't want to wait till the acne [9:01] returns. Actually, go ahead and see your [9:03] dermatologist before any medication [9:06] changes that might impact your skin. So, [9:08] they can initiate other therapies to [9:11] begin to start working in the skin to [9:13] give you that same level of control and [9:15] cut down on the risk that you have. [9:18] And cut down on the risk that you [9:19] develop worsening of your skin [9:21] condition. If you're developing [9:22] excessive irritation, it may be a [9:24] scenario where you need to use [9:25] moisturizer or consider reducing the [9:28] frequency of cleansing from twice a day [9:30] to once a day. We've talked a lot about [9:32] retinoids today, cuz I think this is [9:34] where people become most concerned that [9:36] they might lose their effect. But what [9:37] about other skin care ingredients? No, [9:40] your skin does not become tolerant of [9:42] the biological effects of skin care [9:44] ingredients. Whether it be your [9:46] antioxidant serums, whether it be your [9:49] exfoliating acids, they all work the [9:51] same way. What changes can be your skin [9:54] or the conditions that your skin is [9:56] existing in. Do you ever need to switch [9:58] up your skin care products, however? For [10:02] example, if you have been using a [10:04] topical retinoid, [10:05] >> [clears throat] [10:05] >> do you need to switch to another one at [10:07] any point? No. It is not necessary to [10:10] switch up your topical retinoid. [10:13] However, in some cases, someone may find [10:16] that they've developed irritation from [10:18] something in a topical retinoid, in [10:20] which case it might be prudent for your [10:22] dermatologist to prescribe you another [10:24] one. But you don't need to change up the [10:26] topical retinoid that you've been using [10:28] solely to just keep things spicy and [10:30] keep your skin on the edge of its seat. [10:32] I think people way over estimate the [10:35] relative strengths of different [10:37] retinoids and their robustness, their [10:40] potency, when in reality, the [10:42] overwhelming body of evidence suggests [10:44] that for the majority of cases and the [10:46] majority of things, all types of topical [10:48] retinoids, whether it be tretinoin, [10:50] tazarotene, trifarotene, or adapalene, [10:52] if the patient tolerates them and they [10:55] are used consistently, they can achieve [10:57] the same level of control, no matter the [11:00] topical retinoid. So it's more about [11:02] finding and sticking with the topical [11:04] retinoid that you find to be one you can [11:07] stick with, okay? Rather than seeking to [11:10] change it up. Whenever you change things [11:12] up, there's the possibility to introduce [11:14] irritation. It doesn't exert any [11:16] additional control. You don't gain [11:18] anything, in most cases, from going up [11:20] in percentages. I say in most cases [11:23] because when it comes to treating [11:24] disease, sometimes, for example, acne, [11:27] you might start developing thicker acne [11:29] spots, in which case maybe a higher [11:31] percentage does deliver a little bit [11:33] more of the retinoid earlier on to allow [11:36] you to get better control faster, but [11:38] that's not even necessarily always the [11:40] case. For whatever reason, some people's [11:42] skin disease does respond better to [11:44] different retinoids, but that's not [11:47] something that necessarily changes over [11:49] time per se. Don't confuse a plateau [11:52] with resistance. Just because the skin [11:54] is no longer looking as good as you felt [11:56] it once did on the given regimen, [11:58] doesn't mean that the ingredient is no [12:01] longer working. It just means maybe you [12:03] need something additional, maybe you [12:04] need to change something else up in your [12:06] routine, or maybe you just need to ride [12:08] it out. In other words, when skin [12:10] problems return, you need to ask why [12:12] they returned. Are you still using the [12:14] active treatment as frequently? And a [12:16] good way to hold yourself accountable is [12:18] in the case of prescription medications, [12:20] have you been finishing and refilling [12:22] your prescription as prescribed? If not, [12:26] if you find it's been a lot longer since [12:28] you've needed to refill, that's a clue [12:30] that you're probably not using it as [12:32] consistently as you might think that you [12:35] are. Have you undergone any hormonal [12:37] changes or medication changes? Is there [12:39] a change in the pattern in which your [12:42] skin is erupting? For example, maybe you [12:44] once dealt with acne breakouts on your [12:46] face that are now really well [12:48] controlled, and maybe now you're [12:49] breaking out a lot along the jawline. Or [12:51] maybe rather than your face, it's coming [12:54] also on your body. Also, not everything [12:56] that looks like acne is acne. This is a [12:59] common issue people self-diagnose when [13:03] in reality they might have something [13:05] entirely different going on. And that [13:06] holds true with other skin conditions [13:09] like eczema, for example, atopic [13:11] dermatitis. You can develop other skin [13:13] problems on top of that that look like [13:15] the disease is getting worse, when in [13:17] reality you have a whole new disease [13:19] process that needs to be addressed. [13:21] Bottom line, skin care ingredients do [13:23] not stop working. You don't necessarily [13:26] need to pursue another version of that [13:28] ingredient. There are a variety of [13:30] things that need to be taken into [13:31] account as to why it is that you might [13:33] not be responding like you once did to a [13:36] given regimen. The best way to figure [13:38] that out is to you see your [13:40] dermatologist in the case of [13:41] prescription topical, especially those [13:43] being used to treat and control [13:45] underlying skin conditions. Don't wait [13:48] until things get so bad that you have no [13:50] other choice but to see your [13:52] dermatologist. Get in and see them or at [13:54] least give them a call. Nowadays with [13:56] the widespread use of telemedicine, [13:57] often times some of these things can be [13:59] handled with a telemedicine visit. So, [14:01] you may not necessarily need to fight [14:04] for that in office treatment window in [14:07] their schedule. They may be able to slip [14:09] you in digitally, take a quick look, and [14:12] come up with a plan for you moving [14:14] forward. All right, y'all. I hope [14:15] today's video was helpful and [14:16] informative in discussing do skin care [14:19] ingredients stop working. Now, on the [14:22] end slate I'm going to put my recent [14:24] video all about can you put topical [14:26] retinoids on the neck. So, check that [14:29] one out next if you missed it. But, if [14:30] you enjoyed today's video, give it a [14:32] thumbs up, share it with your friends, [14:33] and as always, don't forget sunscreen [14:35] and subscribe. I'll talk to you guys [14:37] tomorrow. Bye. [14:57] >> [music]