Progesterone-only contraception is associated with a shorter progression-free survival in premenopausal women with WHO Grade I meningioma

Abstract

The hormonally active nature of intracranial meningioma has prompted research examining the risk of tumorigenesis in patients using hormonal contraception. Studies exploring estrogen-only and estrogen/progesterone combination contraceptives have failed to demonstrate a consistent increased risk of meningioma. By contrast, the few trials examining progesterone-only contraceptives have shown higher odds ratios for risk of meningioma. With progesterone-only contraception on the rise, the risk of tumor recurrence with these specific medications warrants closer study. We sought to determine whether progesterone-only contraception increases recurrence rate and decreases progression-free survival in pre-menopausal women with surgically resected WHO Grade I meningioma. Comparative analysis of 67 pre-menopausal women taking hormone-based contraceptives (progesterone-only medication, n = 21; estrogen-only or estrogen/progesterone combination medication, n = 46) who underwent surgical resection of WHO Grade I intracranial meningioma was performed. Differences in demographics, degree of resection, adjuvant therapy and time to recurrence were compared between the two groups. Compared to patients taking combination or estrogen-only contraception, those taking progesterone-only contraception demonstrated a greater recurrence rate (33.3 vs. 19.6%) with a reduced time to recurrence (18 vs. 32 months, p = 0.038) despite a significantly shorter follow-up (p = 0.014). There were no significant demographic or treatment related differences. The results from this study suggest that exogenous progesterone-only medications may represent a specific contraceptive subgroup that should be avoided in patients with meningioma.

Relationships Between Neurofibromatosis-2, Progesterone Receptor Expression, the Use of Exogenous Progesterone, and Risk of Orbitocranial Meningioma in Females

“…First, we have previously demonstrated in this population that longer exposure of exogenous progesterone was correlated with higher risk of meningioma (21). This was in line with previous study by Harland and associates showing that exogenous progesterone has also been shown to be associated with higher risk of recurrent meningioma (22). Second, our findings that the longer the duration of exogenous progesterone use, the lower the expression of PR, were consistent with previous animal experiment that administering exogenous progesterone would provoke a decrease in progesterone receptors expression (23).…”

Hormone Replacement Therapy in Cancer Survivors – Review of the Literature

“…58-83% of meningiomas express progesterone receptor as opposed to 0-8 % expressing estrogen receptor [104,105]. Inconsistent results of studies indicate various relationship between the different forms of HRT and brain tumours: MHT increases the risk of meningioma by 30-80 %, but not that of glioma [106]; meningiomas can grow as a result of progesterone, estrogen and androgen stimulus [107]; estrogen-only HRT, but not E+P HRT increased the risk of brain tumours, glioma and meningioma in a large UK database of women aged 50-79 [108]; HRT but not oral contraceptive use was associated with an increased meningioma risk [109]; progesterone-only contraception is associated with a shorter progression-free survival i n p r e m e n o p a u s a l w o m e n w i t h W H O G r a d e I meningioma [110]. Taken all these together, it seems to be clear that brain tumours, and especially meningioma and glioma, may be sensitive to estrogen and even more to progesterone, and hormones can stimulate their growth and recurrence, therefore HRT should be avoided in these patients.…”

Meningiomas in Premenopausal Women: Role of the Hormone Related Conditions

“…The studies including patients using progesterone-only contraceptives (17,18,22) have shown increased risk of meningioma in those taking therapy for more than 5 years (17) and in those with PR positive meningiomas (18), and increased risk of recurrence and decrease of the progression free-survival (22). Two patients of our series who currently used progesterone-based contraceptives experienced tumor progression before surgical resection.…”

“…These include the frequent presence of progesterone and estrogen receptors in the meningioma tissue (2-7), the possible association with tumors of the female system (8)(9)(10), the documented changes of the meningioma biology during the menstrual cycle and pregnancy (11)(12)(13), the sometimes reported regression after delivery (14), the in vitro proliferation of meningioma cell lines in culture after exposure of estrogen and progesterone (15,16). Besides, the incidence and risk of meningioma in patients with sex hormonerelated conditions and during the exogenous use of sex hormones for contraceptive therapies have been investigated in several studies (16)(17)(18)(19)(20)(21)(22).…”