Metabolite-Informed Estrogen-Pathway Modulation for Adult Female Acne Remission: A Systems-Based Case Report

Anna Kolomitseva, ND

A case study illustrating how individualized hormone-metabolism targeting, dietary modulation, and circadian stabilization achieved sustained acne remission after oral-contraceptive discontinuation and brief testosterone exposure.

Abstract

Adult female acne often persists or flares despite standard topical and antibiotic therapies, particularly around hormonal transitions such as oral‑contraceptive discontinuation. This case describes a 27‑year‑old woman with inflammatory acne that began ~10 months after stopping a combined oral contraceptive (COC) and worsened around a physician‑prescribed, 5‑week course of exogenous testosterone in late 2023. Baseline conventional labs were unremarkable for hyperandrogenemia or polycystic ovary syndrome (PCOS). A urinary hormone panel suggested low global cortisol output, a 5‑α‑reductase preference, relatively high 2‑hydroxylation of estrogens with low 16‑OH E1, borderline 4‑OH E2, and suboptimal methylation markers. An individualized, stepwise naturopathic plan emphasized a low‑glycemic, dairy‑free dietary pattern; sleep consolidation; and targeted nutraceuticals (magnesium, activated B complex, N‑acetylcysteine, and Vitex agnus‑castus), followed by a defined phase of estrogen‑metabolism support (diindolylmethane and resveratrol) based on urinary steroid metabolite results. Spot topical tea tree oil and simple skin‑care were used; no isotretinoin, spironolactone, or hormonal contraception was initiated. Within six weeks, lesion count and oiliness decreased; after completing the estrogen‑metabolism phase (≈12 weeks), the patient reported clear, “glowing” skin with only rare premenstrual papules when off plan. Remission persisted through the last follow‑up with cycle regularity and improved sleep and energy. This case highlights a systems‑based approach to adult female acne that integrates diet, circadian/sleep care, and hormone‑metabolism targeting when guided by objective patterns.

Introduction

Adult female acne (AFA) is increasingly recognized as a chronic, multifactorial disorder driven by sebaceous androgen signaling, keratinization, Cutibacterium acnes biofilm ecology, diet‑linked insulin/IGF‑1 signaling, and neuroendocrine stress physiology. Contemporary reviews underscore the central role of androgens (including tissue‑level 5‑α conversion to DHT) and diet quality in acne pathogenesis.^1,2

Nutritional patterns with lower glycemic load and selective dairy reduction have shown clinically relevant benefits, and updated dermatology guidance reflects growing attention to diet as part of comprehensive care.

Androgen exposure, endogenous or exogenous, can precipitate or amplify acne activity; this is well‑documented in individuals receiving testosterone therapy.³ These observations help contextualize flares around hormonal transitions, including the period after combined OCP discontinuation when prior ovarian‑adrenal androgen suppression is removed.

We present a case of post‑OCP, adult‑onset acne that worsened after a brief, physician‑prescribed course of exogenous testosterone (not recommended by our clinic) and resolved with a structured, systems‑based naturopathic program personalized to urinary steroid metabolite patterns.

Case Presentation

Patient Profile

A 27‑year‑old woman presented with 18 months of inflammatory facial acne that began approximately 10 months after stopping a 10‑year course of a combined oral contraceptive (discontinued January 2022). In late 2023, under the care of another clinician, she received 5 weeks of exogenous testosterone injections for “low free T,” after which acne and oiliness worsened; therapy was stopped in December 2023. She sought non‑pharmacologic care and wished to avoid restarting OCPs, spironolactone, or isotretinoin.

Relevant history: childhood/teen acne; no hirsutism or virilization; regular menses post‑OCP (cycle length 30–32 days) but premenstrual mood lability and cravings; high job stress; variable sleep (difficulty staying asleep). Prior dermatologic care included benzoyl peroxide 5% and a short trial of an antibiotic wash with minimal benefit.

Symptoms and Examination

At intake (early 2024), she had predominantly inflammatory papules and pustules on the cheeks and T‑zone with intermittent deeper chin lesions premenstrually; oiliness increased. No nodulocystic lesions or scarring. No signs of virilization. No physical exam findings suggested thyroid enlargement or Cushingoid features.

Diagnostic Testing

Conventional labs (2023): A1c 4.6%; TSH 2.22 mIU/L; 25‑OH vitamin D 42.5 ng/mL; SHBG 44.3 nmol/L; estradiol 55 pg/mL; progesterone 0.24 ng/mL (timing uncertain); % free testosterone low. Transvaginal ultrasound previously read as “clear ovaries”; LH/FSH ratio not consistent with PCOS.

Expanded labs (late 2024): Mid‑luteal progesterone 7.37 ng/mL; estradiol 111 pg/mL; iron indices elevated; ANA positive with anti‑RNP 2 (no rheumatologic symptoms); thyroid hormones within reference ranges.

Urinary steroid metabolite testing (late 2024): low global cortisol output; preference for 5‑α‑reductase pathway; relatively high 2‑OH E1 with low 16‑OH E1; high 2‑OH E2 with borderline 4‑OH E2; methylation capacity below optimal; low catecholamine metabolites (VMA/HVA) and low pyroglutamate (glutathione marker).

Interpretation: No biochemical hyperandrogenemia; pattern consistent with peripheral androgen sensitivity (5‑α preference) and catechol‑estrogen predominance with suboptimal methylation.

Timeline

2012–Jan 2022: On combined OCP with good acne control.

Jan 2022: OCP discontinued.
Nov 2022: Acne onset (papulopustular); minimal response to OTC benzoyl peroxide/antibiotic wash.
Nov–Dec 2023: 5 weeks of physician‑prescribed testosterone injections; acne/oiliness worsened; therapy stopped.
Feb–Mar 2024: Intake with initiated Phase 1 (diet/sleep + core nutrients + Vitex; simple topical care).

Apr–May 2024 (6–10 weeks): Fewer inflammatory lesions; less oiliness; improved sleep; cycles 30–32 days.
Oct–Nov 2024: Labs & urinary steroid metabolite testing; begin 7‑day liver‑reset, then Phase 2 (estrogen‑metabolism support).
Jan 2025 (~12 weeks into Phase 2): Patient reports clear skin; rare premenstrual papules if off plan.

Mar–Aug 2025: Maintenance; sustained remission; step‑down to core supports; lifestyle plan continued.

Differential Diagnosis

• Adult female acne (hormone‑sensitive acne vulgaris): favored by adult onset after OCP discontinuation, premenstrual clustering, seborrhea, and 5‑α preference without biochemical hyperandrogenemia.
• Exogenous‑androgen–associated acne: temporally associated worsening during testosterone injections.
• Polycystic Ovarian Syndrome: considered historically but less likely due to regular cycles, normal ovarian ultrasound, no biochemical hyperandrogenism, and no ovulatory dysfunction on mid‑luteal testing.
• Acneiform drug eruption: no culprit medications identified.
• Rosacea: distribution and comedones favored acne; no fixed centrofacial flushing or telangiectasias.
• Secondary endocrinopathies (eg, CAH, hyperprolactinemia): not supported by history or labs.

Interventions

Treatment Overview

Care progressed in two structured phases with maintenance thereafter, summarized in Table 1.

Phase 1 (Foundations; 8–12 weeks). We first stabilized diet, sleep, and topical care. Nutrition emphasized low‑glycemic, fiber‑rich meals with removal of liquid sugars, a time‑limited dairy‑free trial, and explicit protein at each meal.⁵ Sleep hygiene included a fixed wake time, caffeine cut‑off before noon, an evening wind‑down with chamomile/lavender tea, and bedtime magnesium bisglycinate 150 mg/day.^6-9 Core nutrients were an activated B‑complex with P5P 50 mg/day, N‑acetylcysteine 1.8 g/day, and vitamin D 2000 IU/day adjusted to laboratory values.^10-11 For short‑term luteal support and PMS mood, we used Vitex agnus‑castus fruit 500 mg each morning during Phase 1 only.^13,14 Skin care prioritized a gentle, non‑comedogenic cleanser and moisturizer, avoidance of over‑washing, and diluted tea tree oil as a spot antimicrobial for inflammatory lesions.¹⁵

Phase 2 (Hormone–metabolism targeting; ~12 weeks). After foundational steadiness, we implemented a 7‑day whole‑food reset emphasizing crucifers, berries, legumes, hydration, and alcohol cessation, then added metabolism‑supportive nutrients guided by urinary steroid‑metabolite profiling: diindolylmethane 120 mg/day to favor 2‑hydroxylation, resveratrol 1 g/day as an antioxidant adjunct, and methylcobalamin 1000 µg/day for methyl‑nutrient support.¹⁶ Vitex and other adaptogens were paused during this focused metabolism phase to simplify signal attribution. NAC and bedtime magnesium were continued; the diet and sleep plan were maintained.

Maintenance. The patient continued the diet/sleep routine and bedtime magnesium; NAC was tapered to the lowest effective dose. A cautious dairy re‑challenge was discussed but ultimately avoided due to reproducible flares. Vitex was reserved for any future PMS‑mood recurrence, and zinc was deferred unless intake proved low and GI tolerance acceptable.

Rationale

This plan addressed converging drivers relevant to hormonally patterned acne: diet‑linked insulin/IGF‑1 signaling, tissue‑level androgen sensitivity, oxidative stress, estrogen‑metabolite balance, and sleep/circadian stability.

Diet & glycemia. Higher dietary glycemic load and dairy, particularly low‑fat/skim, are associated with acne activity via insulin/IGF‑1 and downstream mTORC1 signaling; shifting toward lower‑glycemic, fiber‑rich meals while removing liquid sugars and dairy reduction is therefore a rational first‑line lever.^4,5

Sleep & circadian. Sleep consolidation supports neuroendocrine balance and adherence. Evidence‑based routines are recommended for insomnia; caffeine within ~6 hours of bedtime impairs sleep continuity; chamomile tea has improved sleep quality in adults; and magnesium is commonly used at bedtime with a favorable safety profile, hence our choice of bisglycinate at night.^6-9

Targeted nutrients. N‑acetylcysteine was selected for its antioxidant and keratinization‑modulating effects, with supportive signal in a systematic review of acne.¹⁰ Vitamin D was replenished to sufficiency based on labs and supported by a recent randomized, double‑blind trial showing clinical improvement when used adjunctively with topical therapy.¹² The activated B‑complex (with P5P) was positioned for general cofactor support in women’s health rather than as a primary acne treatment.¹¹

Short‑course Vitex. Vitex agnus‑castus was used briefly for PMS‑mood and luteal symptoms, guided by a placebo‑controlled clinical trial and recent receptor‑level work demonstrating dopamine‑D2 interactions consistent with pituitary modulation; given limited acne‑specific data, Vitex was paused during the metabolism‑focused phase.^13,14

Topical strategy. To complement barrier‑friendly cleansing and moisturizing, diluted tea tree oil was used as a spot antimicrobial; a 2023 systematic review of randomized trials supports clinical utility and acceptable safety when appropriately diluted.¹⁵

Estrogen‑metabolism support (Phase 2). Urinary steroid‑metabolite data indicated an opportunity to favor 2‑hydroxylation; diindolylmethane was used to shift the urinary estrogen profile toward 2‑OH metabolites in premenopausal women, with resveratrol as an antioxidant adjunct and methylcobalamin for methyl‑nutrient support. These selections were mechanistic and personalized to this patient’s biochemical pattern rather than generalized acne therapy.¹⁶

Adjustments

• Vitex and adaptogens were paused during the concentrated estrogen‑metabolism phase.
• Zinc was not routinely added due to GI tolerance and mixed evidence; reserved for dietary insufficiency.
• Skin care remained intentionally simple to avoid irritant dermatitis.

Outcomes and Follow-Up

Early response (6–10 weeks): fewer papules/pustules, decreased oiliness, better sleep continuity, reduced premenstrual cravings; cycles remained regular (30–32 days).

Post‑Phase‑2 (≈12 weeks): patient reported clear skin with a healthy glow; only a rare premenstrual chin papule with dietary lapses. No scarring or post‑inflammatory hyperpigmentation developed.

Sustained remission (≥6 months): maintained on diet/sleep plan, magnesium nightly, and a tapered NAC schedule; she elected to remain dairy‑free given reproducible flares on re‑challenge. No adverse events were reported.

Co‑morbid signals: improved daytime energy and mood stability; normalized sleep latency and maintenance.

Importantly, the short course of exogenous testosterone that coincided with acne worsening was prescribed by another clinician; no exogenous androgens were recommended or administered by our clinic.

Discussion

This case illustrates how a structured, systems‑based naturopathic program can achieve durable acne remission in an adult woman following oral‑contraceptive discontinuation and a brief course of physician‑prescribed exogenous testosterone, without resuming OCPs, spironolactone, or isotretinoin. Her presentation maps onto contemporary models in which diet‑driven insulin/IGF‑1 signaling and tissue‑level androgen sensitivity (including 5‑α‑reductase activity in the pilosebaceous unit) are central, even when serum androgens remain within reference ranges.^2,17

Nutritional therapy consistent with a low‑glycemic, dairy‑reduced pattern is supported by randomized and review‑level evidence and is increasingly reflected in guideline discussions. In adults, higher‑glycemic loads and certain dairy exposures (notably low‑fat/skim) correlate with greater acne severity, whereas low‑glycemic patterns are associated with improvement.^2,5 Recent U.S. guidelines also counsel clinicians to discuss diet in the context of evidence signals and patient preference.¹⁸

Phase‑2 “hormone‑metabolism targeting” was guided by urinary steroid‑metabolite patterns and anchored to emerging clinical and mechanistic literature. In a recent clinical study, diindolylmethane shifted urinary estrogen‑metabolite ratios toward greater 2‑hydroxylation in premenopausal women, aligning with the intended biochemical direction of our intervention.¹⁶ Resveratrol, while not an acne drug, has laboratory evidence of down‑regulating CYP1B1 and reducing catechol‑estrogen quinone formation, mechanisms pertinent to individuals with higher 4‑hydroxylation tendencies.¹⁹

Adjuncts were selected for plausibility and patient preference. N‑acetylcysteine has emerging, albeit limited, clinical evidence for acne via antioxidant and anti‑inflammatory effects.¹⁰ For topical care in patients minimizing multi‑agent regimens, tea tree oil retains supportive human data from randomized trials across dermatologic indications and has been used as a spot adjunct in acne.¹⁵

Overall, this case adds to a pragmatic body of work showing that targeted nutrition, sleep consolidation, and carefully chosen adjuncts can meaningfully modulate diet‑hormone‑skin axes. It also underscores the importance of timing and context around androgen exposure, and the value of data‑guided iteration (e.g., metabolite‑informed use of DIM and antioxidant support) within an integrative dermatology framework.

Conclusion

A structured, systems‑based naturopathic program anchored in diet quality, sleep/circadian consolidation, and targeted nutraceuticals produced sustained acne remission after oral‑contraceptive discontinuation and brief physician‑prescribed testosterone exposure, without resuming OCPs, spironolactone, or isotretinoin. Urinary hormone‑metabolite testing informed phase‑2 estrogen‑metabolism support, while removal of individualized triggers (liquid sugars, dairy, late eating, poor sleep) stabilized flares. For selected adult female acne patients without overt hyperandrogenemia, lifestyle‑first care with selective hormone‑metabolism support can deliver durable outcomes and lessen reliance on pharmacologic escalation. Prospective studies should test this staged sequence (foundations to metabolism targeting) using standardized clinical and biochemical endpoints.

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