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Photodynamic Endometrial Ablation in the Nonhuman Primate

Departments of Obstetrics and Gynecology, Physiology, and Pathology, Queen's University, Kingston, Ontario, Canada; Health Canada, Ottawa, Ontario, Canada; and DUSA Pharmaceuticals Inc., Valhalla, New York vanugtd{at}post.queensu.ca

Alicja Krzemien, MD

Brenda N. Roy, PhD

William A. Fletcher, MD

Warren Foster, PhD

Scott Lundahl, MSc

Stuart L. Marcus, MD

Robert L. Reid, MD

Departments of Obstetrics and Gynecology, Physiology, and Pathology, Queen's University, Kingston, Ontario, Canada; Health Canada, Ottawa, Ontario, Canada; and DUSA Pharmaceuticals Inc., Valhalla, New York

Objective: To test the effectiveness of 5-aminolevulinic acid (ALA)-induced photodynamic endometrial ablation in the rhesus monkey under varying conditions of light delivery (fractionated versus continuous) and steroid priming.

Methods: Photodynamic endometrial ablation was carried out in 17 rhesus monkeys that were either postmenopausal or in the early proliferative phase. Four hours after intralumental injection of ALA (250 mg in 1 mL hyskon), a quartz fiber with a diffusing tip was inserted. A KTP tunable dyye laser delivered 300 mW of light (635 nm) for 60 minutes in either continuous or fractionated fashion (20 minutes on, 5 minutes off, and 40 minutes on). In some experiments, thermistors were used to monitor temperature in the lumen and myometrium during light treatment. Hysterectomy was performed 3 or 4 days after treatment, and endometrial damage was assessed histologically. Two additional monkeys (one rhesus and one cynomolgus monkey) were exposed to the same protocol, except hyskon was substituted for ALA to control for potential ablative effects due to light treatment alone.

Results: Endometrial ablation was evident in all ALA-photosensitized specimens. The degree of ablation around the light fiber ranged from moderate to complete. The depth of ablation ranged from 1.14 ± 0.54 to 2.15 ± 1.62 mm (mean ± standard deviation). Ablation was most complete in uteri of menopausal monkeys. Light treatment after ALA increased leumenal temperature from 36C to 50C, whereas temperature was not significantly increased by light treatment in the controls.

Conclusion: This is the first report of endometrial destruction in the primate using a photodynamic approach. Whereas clinical application of photodynamic therapy (PDT) requires complete endometrial ablation to produce long-lasting amenorrhea, our results suggest that PDT may offer a simple office-based approach to endometrial ablation.

Key Words: Photodynamic ablation • endometrium • 5-aminolevulinic acid • menstrual cycle • dysfunctional uterine bleeding

Journal of the Society for Gynecologic Investigation, Vol. 7, No. 2, 125-130 (2000)
DOI: 10.1177/107155760000700208


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