Endometrial cancer is frequently hormone-responsive, yet synthetic progestins are rarely used in high-risk histologies such as serous or clear-cell carcinomas. Micronized (bio-identical) progesterone is commonly employed in naturopathic practice for sleep support due to its GABA-A receptor activity. This report describes two postmenopausal women with advanced or recurrent high-risk endometrial cancer in whom oral micronized progesterone was integrated primarily for sleep, quality-of-life improvement, along with its anti-cancer potential included within a broader naturopathic oncology program that included dietary optimization, supplementation, exercise, lower dose intravenous vitamin C-based nutrition, intravenous mistletoe, and in one case repurposed agents.
Case 1: Active Surveillance in Recurrent p53-Abnormal Serous Endometrial Cancer
A 75-year-old Korean woman with a history of FIGO stage IB p53-mutated serous endometrial adenocarcinoma (mismatch-repair proficient, POLE wild-type) underwent total laparoscopic hysterectomy with bilateral salpingo-oophorectomy and staging in February 2022, followed by six cycles of carboplatin/paclitaxel and pelvic external-beam radiation. In August 2024, she developed biopsy-proven recurrence in the left supraclavicular lymph nodes and received palliative radiotherapy (30 Gy/5 fractions). In December 2024, PET/CT revealed new FDG-avid right para-aortic disease, also treated with palliative radiotherapy (30 Gy/5 fractions, January 2025). She declined further standard systemic therapy and elected active surveillance.
She began naturopathic oncology care in December 2024. Her program included a Mediterranean-style whole-foods diet, regular exercise, intravenous vitamin C (7500mg), mistletoe injection (Helixor M 100mg), repurposed oral mebendazole, and a short trial of methylene blue. After trazodone failed to improve sleep, oral micronized progesterone 200 mg at bedtime was initiated in April 2025. Sleep quality improved markedly within days. She continues an alternating regimen of 200 mg one night and 100 mg the next in keeping with the lowest-effective dose approach, with sustained benefit and no adverse effects. She also continues with mebendazole 100mg twice daily. As of July 2026, serial imaging demonstrates disease stabilization. Estrogen and progesterone receptor status was never assessed by her oncology team.
Case 2: Dramatic Response with Integrated Pembrolizumab, Lenvatinib, and Micronized Progesterone
A 56-year-old Black woman of Caribbean descent presented with FIGO stage IVB high-grade endometrial carcinoma with clear-cell features (p53 wild-type, mismatch-repair proficient, focally estrogen-receptor positive) and progressing pulmonary nodules. She completed seven cycles of carboplatin/paclitaxel in February 2024 with limited benefit.
Naturopathic care began in April 2024 with the similar core program described above. Micronized progesterone 100 mg nightly was started in May 2024 for sleep and anxiety as well as potential anti-cancer properties. Due to insufficient symptom response, the dose was increased to 200 mg nightly in June 2024. A brief interruption occurred because of pharmacy confusion. CT imaging in November 2024 showed pulmonary progression, prompting initiation of pembrolizumab plus lenvatinib. Initial dosing was poorly tolerated, requiring emergency evaluation for pancreatitis in December 2024 and a treatment pause. On March 26, 2025, she completed palliative radiation to the left iliac node and right retroperitoneal mass.
“Could bioidentical progesterone offer benefits beyond sleep support in advanced endometrial cancer?”
Micronized progesterone 200 mg nightly continued together briefly with trazodone 50 mg, and was later switched to Lemborexant 30mg, leading to significantly improved sleep quality. At the end of April 2025, a reduced dose lenvatinib regimen with pembrolizumab was restarted. By July 2025, imaging demonstrated near-complete resolution of pulmonary and hepatic metastases. As of July 2026, she continues reduced-dose lenvatinib, pembrolizumab, micronized progesterone 200 mg nightly, intravenous vitamin C (2500mg), and mistletoe (Helixor M 100mg). The patient is also taking a daily oral wildcrafted sea moss preparation of Jamaican origin. She remains without evidence of disease progression and reports good quality of life despite lenvatinib-associated hypertension and pembrolizumab-induced hypothyroidism.
Both patients identify strong religious faith as an important supportive factor in their healing journeys.
Discussion
Synthetic progestins remain a guideline-supported option for advanced or recurrent endometrial cancer, particularly low-grade endometrioid tumors, with objective response rates of approximately 20–30% and clinical benefit rates of 35–52% in meta-analyses.¹,² Higher responses occur in progesterone-receptor-positive disease. Despite these data, progestins are infrequently utilized in high-risk histologies, and hormone-receptor testing is often omitted in standard oncology practice. Micronized progesterone offers a chemically identical alternative to endogenous progesterone with potentially improved tolerability compared with synthetic progestins, which carry additional glucocorticoid, androgenic, or mineralocorticoid activity. In menopausal hormone therapy, cyclic oral micronized progesterone (200 mg for 12–14 days per month) provides effective endometrial protection.³ Direct therapeutic data in established advanced endometrial cancer are lacking; the only ongoing trial we found was comparing micronized progesterone with megestrol acetate in a pre-surgical “window-of-opportunity” study (NCT07436793).⁴
In the cases presented, micronized progesterone was chosen primarily to address sleep disturbance—a common and quality-of-life-limiting symptom in cancer patients—in addition to the anti-cancer potential properties. Doses of 100–200 mg nightly were well tolerated. We did not try higher doses (>200mg) but may consider it in the future. In the first case, monotherapy within an active-surveillance and naturopathic framework coincided with disease stabilization in recurrent serous carcinoma. In the second case, integration with approved immunotherapy plus anti-angiogenic kinase regimen coincided with an exceptional radiographic response in a focally estrogen-receptor-positive tumor. These observations are hypothesis-generating. Potential mechanisms include direct progesterone-receptor-mediated differentiation and apoptosis, improved treatment tolerance through better sleep, and possible supportive effects within a multimodal integrative program. Limitations include the absence of progesterone-receptor testing, confounding multimodal interventions, and the observational nature of case reports. Nevertheless, these cases illustrate a practical, patient-centered approach that prioritizes quality of life while exploring bio-identical hormonal support in settings where synthetic progestins are rarely considered.
Conclusion
Oral micronized progesterone, used principally for sleep support, was safely incorporated into the care of two women with advanced high-risk endometrial cancer. One patient on active surveillance experienced continued disease stabilization; the other achieved a dramatic response when combined with standard immunotherapy and targeted kinase therapy. These reports support further exploration of bio-identical progesterone as a tolerable adjunct in naturopathic oncology practice for advanced endometrial cancer, particularly when quality-of-life concerns such as sleep disturbance are prominent.
