Skull Base Meningiomas as Part of a Novel Meningioma Syndrome Associated with Chronic Depot Medroxyprogesterone Acetate Use

Objective: Chronic progestin use has been recently recognized to be associated with a unique set of shared features meningioma patients. While most studies on this topic are emerging from Europe, this entity has not been described in the United States and specifically with chronic depot medroxyprogesterone acetate (DMPA) use. The aim of this study is to describe a series of adult female patients with chronic DMPA use presenting with a similar pattern of meningiomas including skull base meningiomas.

Methods: The authors performed a retrospective review of meningioma patients with a history of DMPA use treated at the University of Pittsburgh Medical center between 2014 and 2021. Clinical and radiographic data as well as duration of consistent DMPA use were reported. Histopathological and immunohistochemical examinations of resected meningiomas was performed.

Results: During the study period, 25 female patients with a mean age of 46 years were identified to harbor one or more intracranial meningiomas related to chronic DMPA use ([Fig. 1]). There were 49 total meningiomas (range: 1–6 meningiomas per patient). The mean duration of DMPA use was 15.5 years (range: 6–26). Seventeen (68%) patients had at least one skull base meningioma located in the spheno-cavernous-orbital, spheno-cavernous, spheno-orbital, or orbital region. Histopathological examination of the 47 resected meningiomas identified that 36 (77%) were WHO grade I, 11 (23%) were WHO grade II and the mean K_i-67 proliferation index was 2.2% (range: 1–5%). Progesterone immunohistochemical staining was performed on all meningiomas and all tumors stained positively for it. Interestingly, 10 patients were instructed to stop DMPA that had either an untreated meningioma or a clear (≥1 cm) residual following surgical intervention. Among these 10 patients, 5 had clear evidence of tumor shrinkage, 2 were lost to follow-up, and 3 stopped DMPA within the past year not allowing for adequate assessment at this time.

Conclusions: There appears to be a clear progestin meningioma syndrome associated with chronic DMPA use. Patients with DMPA-associated meningiomas tend to be younger, middle-aged women with multiple meningiomas, of which one is commonly located at the skull base (sphenoid wing, orbit, and/or cavernous sinus). The meningiomas tend to be low grade meningiomas and often invade underlying bone and express progesterone receptor on immunohistochemical staining. Females that fit these criteria should be screened and counseled for progestin use. The agent should be stopped immediately, and the patient should be closely followed before other treatments are entertained.

Fig. 1 Preoperative axial T1-weighted postcontrast MRI depicting multiple osseous meningiomas highlighted by white arrowheads including left petrous apex (A) right spheno-cavernous orbital (A, B, C), and left spheno-orbital (A, B, C) meningiomas and multiple convexity meningiomas highlighted by white arrows (B, C, D, E) including a large right frontoparietal vertex meningioma (E). There is also a corresponding axial pre-contrast bone CT comparison depicting osseous involvement of right spheno-cavernous orbital and left spheno-orbital meningiomas (F).

Publication History

Article published online:
01 February 2023