Estrogen and Progesterone Therapy and Meningiomas

Meningiomas are common intracranial tumors with female predominance. Their etiology is still poorly documented. The role of sexual hormones has long been evoked, and data have been conflicting across studies. However, a dose-dependent relationship between the incidence and growth of meningiomas and hormonal treatment with the progestin cyproterone acetate (CPA) has recently been established. CPA- associated meningiomas seem to be mainly located in the anterior and middle skull base, are more likely to be multiple; may harbor P1K3CA mutations in up to 1/3 of cases and are favored by a longer duration of treatment. A similar but lower risk of meningiomas has been recently reported with the use of chlormadinone acetate and nomegestrol acetate as progestin treatments. Concerning hormonal replacement therapy (HRT) in menopausal patients, evidence from epidemiological studies seem to favor an increased risk of meningiomas in treated patients although a recent study failed to show an increased growth of meningiomas in HRT treated vs. non treated patients. Until larger studies are available, it seems wise to recommend avoiding HRT in patients with meningiomas. Evidence from published data does not seem to support an increased risk of meningiomas with oral contraceptive (OC) use. Data are too scarce to conclude on fertility treatments. Based on studies demonstrating the expression of hormonal receptors in meningiomas, therapies targeting these receptors have been tried but have failed to show an overall favorable clinical outcome in meningioma treatment.

Pilot Data on the Feasibility And Clinical Outcomes of a Nomegestrol Acetate Oral Contraceptive Pill in Women With Premenstrual Dysphoric Disorder

BackgroundUp to 80% of reproductive-aged women experience premenstrual symptoms. Premenstrual Dysphoric Disorder (PMDD) is a severe form, affecting 2-5% of women. Combined oral contraceptive pills (COCPs) are used in the treatment of PMDD. Clinical practice suggests that a newer COCP containing nomegestrol acetate (2.5mg) and 17-beta estradiol (1.5mg), may be a suitable treatment for mood symptoms in PMDD.Materials and MethodsThis was a clinical follow-up feasibility study of women who had attended the Monash Alfred Psychiatry research centre, Women’s Mental Health Clinic, with a diagnosis of PMDD. 67% of the sample also had concurrent cPTSD, 29% co-morbid anxiety, and 20% depression. They were recommended treatment with nomegestrol acetate/17-beta estradiol. Eligible women were contacted by telephone to answer a questionnaire to assess women’s subjective response to nomegestrol acetate/17-beta estradiol, acceptability and the Depression, Anxiety and Stress Scale-21 (DASS-21) after being recommended nomegestrol acetate/17-beta estradiol. The paired-sample t-test was used to determine if there were any statistically significant differences in the DASS-21 scores over the study observation period (before and after taking nomegestrol acetate/17-beta estradiol).Results35 (74.5%) women reported a subjective positive mood response to nomegestrol acetate/17-beta estradiol, 31 (63.3%) adhered to the medication, and only 10 (20.4%) women reported side effects as the main reason for discontinuing nomegestrol acetate/17-beta estradiol. There were statistically significant reductions (p<0.05) in the overall DASS-21 scores from before women commenced nomegestrol acetate/17-beta estradiol and after commencement of treatment.ConclusionsThis preliminary study supports the acceptability and effectiveness of nomegestrol acetate/17-beta estradiol as a treatment for mood symptoms in PMDD. Further research, particularly a randomized controlled trial, is required to elucidate the effect of nomegestrol acetate/17-beta estradiol treatment on mood in PMDD.

Have Progestin Related and Sporadic High Grade Meningiomas the Same Natural History?

Introduction: High grade progestin related meningiomas have been reported in recent series but we found no previous study describing their long-term outcome. Our study aimed to evaluate patients operated on for high grade intracranial meningioma and who underwent long term exposure to high dose of cyproterone acetate, nomegestrol acetate and chlormadinone acetate.Methods: Our study retrospectively included 9 patients with high grade progestin related intracranial meningioma between December 2006 and December 2020. In each patient, clinico-radiological follow-up was performed every 6 months after diagnosis and treatment withdrawal recommendation. Results: The mean progestative exposure was 11.4 years. Edema existence or absence of cleft sign on MRI were the key factors for surgical indication. All patients underwent surgery. Ajduvant radiotherapy was indicated in 1 patient, and Gamma Knife Radiosurgery was proposed in 2 other patients for a second location of mengioma. 6 patients harbored a grade II chordoïd meningioma subtype with 100% PR expression and 3 patients a grade II atypical meningioma subtype with lower PR expression. The mean follow-up was 7.1 years and none of the 9 patients presented with a recurrence.Conclusion: Patients with Grade II progestin related meningiomas have less tumor recurrence after surgery than patients with sporadic high grade meningomas, especially after progestin withdrawal. The presence/ appearance of peri-meningioma edema and the absence of cleft sign before volumetric change should suggest the existence of an underlying high grade meningioma. In these cases, surgical resection may immediately be considered and adjuvant radiotherapy should be reserved for proven recurrence cases.

Nomegestrol Acetate or Chlormadinone Acetate Progestative Treatment in Women: Meningioma Behavior at Treatment Discontinuation

The authors have requested that this preprint be withdrawn due to erroneous posting.

Nomegestrol Acetate or Chlormadinone Acetate Progestative Treatment in Women: Meningioma Behavior at Treatment Discontinuation

Background: Associations between progestins and meningiomas is now well established. While the link between cyproterone acetate (CA) and meningioma was thoroughly studied, there is far less available data regarding the link between chlormadinone acetate (CHA) or nomegestrol acetate (NA) and risk of intracranial meningiomaMethods: We are presenting a series of 28 patients diagnosed with single or multiple meningiomas while treated with CHA-NA, in which the clinical and radiological course were analyzed after treatment discontinuation.Results: 28 women, with a mean age of 56 years old, were diagnosed with one or multiple meningioma while being treated with either CHA or NA. After stopping treatment, 89.3% showed either tumor shrinkage or tumor stabilization on follow-up MRIs. Multiple meningiomas were more likely observed in patients with long periods of treatment (>10 years, p 0.03) and seem to have a better clinical course (p 0.01). Most of the lesions were located on the skull base (55.4%). Four patients with multiple meningiomas showed discordant tumors evolution, with some tumors growing while others were decreasing. Most of the growing meningiomas were either convexity or midline lesions and more posteriorly located. Conclusion: Our study demonstrated a significant percentage of tumor diminution or stabilization after NA and CHA discontinuation. Therefore, treatment discontinuation with close monitoring should be the first measure taken if urgent surgery is not indicated. However, our results seem to be less encouraging than previously described in patients treated by CA, with more patients showing tumor growth despite treatment discontinuation. Further studies are needed to differentiate the effect of the different progestins treatment on meningiomas.

Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study

Background: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy. Objective: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo. Methods: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo. Results: Recruitment was stopped prematurely due to slow inclusions ( n = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58–1.39), placebo = 0.97 (0.63–1.50) ( p = 0.79)). Conclusion: POPARTMUS failed showing efficacy of a NOMAc–E2 combination in preventing post-partum relapses.