Stella+

• Stimulates collagen and elastin production — estriol and GHK-Cu both independently activate fibroblasts to rebuild the skin's structural proteins, while tretinoin further drives collagen synthesis through retinoid receptor signaling ^1 2 3
• Reduces fine lines and wrinkles — research on 0.3% topical estriol, tretinoin, and GHK-Cu has each independently shown measurable reductions in wrinkle depth and surface area ^1 2 5
• Improves skin thickness and density — topical estriol counteracts the epidermal thinning associated with estrogen deficiency, and GHK-Cu has been shown to increase dermal density and firmness ^1 6
• Enhances skin hydration and barrier function — estriol boosts hyaluronic acid production, niacinamide supports ceramide synthesis, and tretinoin improves the stratum corneum's ability to retain moisture ^4 7
• Evens skin tone and reduces hyperpigmentation — tretinoin normalizes melanocyte activity and speeds cell turnover; niacinamide inhibits melanin transfer to the skin surface; estriol supports overall pigmentation regulation ^3 4
• Supports skin maintenance and regeneration — GHK-Cu activates multiple tissue repair pathways, attracts macrophages and mast cells, and promotes new blood vessel formation, accelerating recovery from environmental damage ^2 6
• Reduces skin inflammation — GHK-Cu has demonstrated meaningful anti-inflammatory effects in dermal fibroblasts; niacinamide suppresses pro-inflammatory cytokines; lower-dose tretinoin (0.01%) is generally well tolerated with reduced irritation compared to higher concentrations ^2 4 5
• Addresses hormonal skin aging at its root — rather than treating surface symptoms alone, estriol restores estrogen receptor signaling in the dermis, where postmenopausal skin loses up to 30% of its collagen in the first five years after menopause ^1 7

Potential Side Effects

Potential side effects are most common during the first 4–6 weeks of use as the skin adjusts to the retinoid component. Most are mild and temporary.⁵

Common possible side effects:

• Dryness, flaking, or mild peeling — especially in the first 2–6 weeks; usually resolves with continued use and a good moisturizer
• Redness or warmth at the application site — more common with nightly use; alternating nights can help during the initial adjustment
• Mild stinging or tingling immediately after application
• Increased sun sensitivity — use of daily broad-spectrum SPF 30+ sunscreen is essential while using this cream
• Skin purging — a temporary increase in breakouts during the first 4–6 weeks as tretinoin accelerates cell turnover; this is not an allergy and typically resolves

Less common possible side effects:

• Hyperpigmentation or darkening at the application site — this can occur if the skin is irritated and then exposed to UV light; strict sun protection helps prevent this
• Contact dermatitis or allergic reaction — rash, hives, or significant swelling; discontinue use and contact the prescriber if this occurs

Warnings and Precautions

• Apply sunscreen every morning — this is non-negotiable while using any tretinoin product; sun exposure while using tretinoin can worsen photosensitivity and increase the risk of irritation and hyperpigmentation
• Start with every-other-night application and increase to nightly as tolerated — "start low and go slow" reduces the risk of initial retinoid irritation
• Avoid waxing, laser treatments, chemical peels, or dermabrasion to areas being treated with Stella+ without first consulting the prescriber — tretinoin makes the skin more vulnerable to procedures
• Do not use near heat sources (e.g., heating pads, saunas) immediately after applying — increased blood flow to the skin may increase absorption and irritation
• Inform all healthcare providers that this cream is being used, especially before undergoing any facial procedures
• Do not apply during periods of significant skin barrier disruption (e.g., after laser resurfacing, chemical peels, or active sunburn) without specific provider guidance

Contraindications

Stella+ should not be used in the following situations without explicit guidance from a prescriber:

• Known or suspected pregnancy — tretinoin is a known teratogen (category X for systemic use) and topical use during pregnancy is generally contraindicated; estriol is also contraindicated in pregnancy
• Breastfeeding — use with caution; consult the prescriber
• Known allergy or hypersensitivity to estriol, tretinoin, GHK-Cu, niacinamide, or any other ingredient in the formulation
• History of estrogen-sensitive cancers (e.g., breast cancer, endometrial cancer) — use only under explicit specialist guidance due to the estriol component
• Active eczema, rosacea flare, seborrheic dermatitis, or significant skin barrier disruption at the intended application site — wait for resolution before initiating Stella+.
• Active facial infections (bacterial, viral, or fungal) at the application site

Drug Interactions

Stella+ is a topical cream with low systemic absorption, which limits the risk of systemic drug interactions. However, local skin interactions and the estriol component should be considered.⁸ Interactions to be aware of include:

• Other topical retinoids (tretinoin, adapalene, tazarotene, retinol products): Combining Stella+ with additional retinoid-containing products dramatically increases irritation risk — use only as directed and do not layer with other retinoid preparations
• Topical AHAs or BHAs (glycolic acid, salicylic acid, lactic acid): These exfoliants can compound retinoid-induced skin barrier disruption; avoid on the same nights as Stella+ until the skin has fully adapted⁵
• Benzoyl peroxide: Can oxidize and inactivate tretinoin — do not apply at the same time or on the same nights
• Products containing medicated or astringent ingredients (witch hazel, high-dose vitamin C, alcohol-based toners): May increase skin dryness and sensitivity when used alongside tretinoin³
• Systemic estrogen therapy (oral or transdermal): Because Stella+ contains topical estriol, patients already using systemic hormone therapy should inform their prescriber so that total estrogen exposure can be considered; systemic absorption of 0.3% topical estriol is generally low but should be acknowledged in the context of overall hormone management⁸

Stella+ works through three complementary and synergistic pathways, each targeting a different aspect of skin aging. Think of the skin as a building: estriol is the architect restoring the building's structural blueprint; GHK-Cu is the construction crew actively working and rebuilding the walls; and tretinoin is the renovation manager, accelerating turnover and clearing out old, damaged material to make room for the new.

Estriol (0.3%) works by binding to estrogen receptors in the skin — primarily estrogen receptor beta (ERβ) — which are found in high concentrations in dermal fibroblasts, the cells responsible for producing collagen and elastin.¹ When estrogen levels fall after menopause, fibroblast activity slows, collagen synthesis declines, and the skin thins and loses elasticity. Topical estriol restores this signaling locally, without the systemic exposure associated with oral hormones. At 0.3%, it has been shown in clinical studies to increase epidermal thickness, improve skin elasticity, and reduce wrinkle depth, with minimal systemic absorption.⁷

GHK-Cu (3%) is a copper-peptide complex naturally found in human blood plasma, where its levels drop from roughly 200 ng/mL at age 20 to about 80 ng/mL by age 60.⁶ When applied to the skin, GHK-Cu penetrates the outer layer and activates fibroblasts to produce collagen, elastin, and glycosaminoglycans — the molecules that give skin its density and moisture. Importantly, it also regulates enzymes called matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), carefully balancing collagen breakdown and rebuilding to produce a net gain in dermal tissue.² In a double-blind clinical trial, GHK-Cu reduced wrinkle volume by 31.6% compared to a comparator cosmetic peptide over 8 weeks. GHK-Cu is also a potent anti-inflammatory, reduces oxidative damage, and supports new blood vessel formation — all of which support skin maintenance and a youthful appearance.²

Tretinoin (0.01%) is the prescription-strength, active form of vitamin A. It works by binding to retinoic acid receptors in skin cells, directly activating genes that control cell differentiation, proliferation, and collagen production.³ It accelerates the natural turnover of skin cells (corneocytes), pushing older, sun-damaged cells to the surface and off, while encouraging the growth of new, healthier cells beneath. It also compacts the stratum corneum, the outermost skin layer, making it smoother, denser, and able to retain moisture. Tretinoin at 0.01% is the gentlest prescription concentration — sufficient to provide meaningful benefits while minimizing the dryness and peeling associated with higher strengths.⁵

Niacinamide, the vehicle-based supportive ingredient, plays a complementary role: it minimizes inflammation (helping the skin tolerate tretinoin's initial adjustment period), inhibits the transfer of melanin to skin surface cells (supporting even tone), boosts ceramide production to reinforce the skin barrier, and offers mild antioxidant protection.⁴ The combination of all four ingredients in a single cream creates a layered, multi-mechanism approach to skin restoration that no single ingredient alone can replicate.

Q: Is there a best time of day to apply Stella+?

A: Stella+ should always be applied at night. The tretinoin in Stella is light sensitive and will degrade in daylight. Tretinoin may also cause skin irritation, and is better tolerated while a patient is asleep.

Q: How can I minimize potential side effects?

A: The tretinoin in Stella+ may cause a transient increase in irritation. The inclusion of niacinamide in our formulation not only amplifies tretinoin's benefits, but helps with tolerability. Night time application will also address any perceived irritation. Your provider may also have you titrate the medication, using it less frequently at first and gradually increasing frequency as tolerated.

Q: What makes Stella+ different from regular skincare products?

A: Most over-the-counter skincare products work on the surface of the skin — hydrating, temporarily plumping, or providing antioxidant protection. Stella+ works differently. It contains three prescription-strength active ingredients that work at the cellular level to address the root causes of skin aging: hormonal decline, collagen loss, and reduced cell turnover.^1 3 Because it is compounded specifically for each patient by prescription, the formulation can be adjusted to fit individual skin needs in ways that mass-market products simply cannot.

Q: Who is Stella+ intended for?

A: Stella+ is designed primarily for peri- and postmenopausal women whose skin is showing signs of hormonal aging: thinning, increased dryness, sagging, fine lines, and uneven tone. It may also be appropriate for adults with significant photodamage or premature skin aging. It requires a prescription and a healthcare provider's assessment to determine whether it is a good fit.¹

Q: Can Stella+ be used on the neck and chest, not just the face?

A: Stella+ may be used on the neck and décolletage as directed by the prescriber. These areas also contain estrogen receptors and are commonly affected by hormonal skin aging. Skin in these areas is often thinner and more sensitive than the face, so beginning with every-other-night application and monitoring for irritation is especially important. Always discuss expanded use areas with the prescribing provider before proceeding.

Q: Does Stella+ count as hormone therapy?

A: Stella+ contains estriol at 0.3%, which is a very low concentration designed for localized facial application. Studies on topical facial estriol at this concentration have not shown meaningful increases in systemic estrogen levels.⁷ However, because it is a prescription estrogen, it should be disclosed to all healthcare providers.

Q: Is the tretinoin in Stella+ strong enough to make a real difference?

A: Tretinoin 0.01% is the gentlest prescription concentration of tretinoin. Some studies have found that 0.01% alone — as a standalone product — did not produce statistically significant photoaging improvements in all trials.⁵ However, in Stella+ formulation, it works synergistically with estriol and GHK-Cu, both of which also independently stimulate collagen and skin renewal through different pathways. The combined effect of all three ingredients is expected to be meaningfully greater than any single ingredient used alone. Additionally, 0.01% tretinoin is far better tolerated than higher concentrations, making it suitable for long-term consistent use — which is ultimately what produces results.³

IMPORTANT INFORMATION ABOUT COMPOUNDED MEDICATIONS

This medication has been compounded (custom-prepared) by a pharmacy. Compounded medications are specially prepared for individual patient needs based on a valid prescription and, as such, are not reviewed or approved by the U.S. Food and Drug Administration (FDA) for safety or efficacy. These statements have not been evaluated by the FDA.

This compounded preparation:

• Has not been approved by the FDA
• Has not undergone FDA review for safety, effectiveness, or quality
• Is prepared specifically for you based on your prescriber's order
• Individual outcomes may vary

Dosing is determined by the prescribing provider based on patient-specific factors. Always follow your healthcare provider's instructions. Compounded medications are not subject to FDA approval and lack the same safety and efficacy data as FDA-approved commercial medications. This medication should be prescribed and monitored by a licensed healthcare professional familiar with the condition being addressed and the specific applications of the medication.

1. Lephart ED, Naftolin F. Estrogen action and skin aging. Dermatology and Therapy. 2021;11(5):1837–1852. doi: 10.1007/s13555-021-00594-w
2. Pickart L, Vasquez-Soltero JM, Margolina A. GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration. BioMed Research International. 2015;2015:648108. doi: 10.1155/2015/648108
3. Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety. Clinical Interventions in Aging. 2006;1(4):327–348. doi: 10.2147/ciia.2006.1.4.327
4. Boo YC. Mechanistic basis and clinical evidence for the applications of nicotinamide (niacinamide) to control skin aging and pigmentation. Antioxidants. 2021;10(8):1315. doi: 10.3390/antiox10081315
5. Siddiqui MZ, Sonthalia S. Topical tretinoin for treating photoaging: a systematic review. International Journal of Women's Dermatology. 2022;8(1):e003. doi: 10.1097/JW9.0000000000000003
6. Pickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide in the light of new gene data. International Journal of Molecular Sciences. 2018;19(7):1987. doi: 10.3390/ijms19071987
7. Schmidt JB, Binder M, Macheiner W, Klade H, Aberer E, Gebhart W. Treatment of skin aging symptoms in perimenopausal females with estrogen compounds: a pilot study. Maturitas. 1994;20(1):25–30. doi: 10.1016/0378-5122(94)90012-4
8. Santoro N, Braunstein GD, Butts CL, Martin KA, McDermott M, Pinkerton JV. Compounded bioidentical hormones in endocrinology practice: an Endocrine Society scientific statement. Journal of Clinical Endocrinology & Metabolism. 2016;101(4):1318–1343. doi: 10.1210/jc.2016-1271