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Purified and specific cytoplasmic pollen extract: a non-hormonal alternative for the treatment of menopausal symptoms

Andrea Genazzaniaa, Nick Panaybb, Tommaso Simoncinicc, Herman Depypereda, Alfred Mueckee,f, Christian Egartergg, Nicoletta Bigliahh, Tomas Faitii, Martin Birkhaeuserjj, Sven O. Skoubykk, Mark Brincatl, Steven Goldsteinmm, Xiangyan Ruanff,e, Cuauhtemoc Celis-Gonzalesnn and Santiago Palaciosoo aDepartment of Gynecology and Obstetrics, University of Pisa, Pisa, Italy; bQueen Charlotte’s & Chelsea and Westminster Hospitals and Imperial College, London, The International Menopause Society, London, UK; cDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; dBreast Clinic and Menopause Clinic, University Hospital, Gent, Belgium; eDepartment of Women’s Health, University Hospitals of Tuebingen, Tuebingen, Germany; fDepartment of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China; gDepartment of Obstetrics and Gynecology, Division of Gynecologic Endocrinology and Reproductive Medicine, University of Vienna, Vienna, Austria; hAcademic Division of Gynecology and Obstetrics, Mauriziano Hospital, University of Turin, Turin, Italy; iDepartment of Obstetrics and Gynecology, Faculty Hospital Motol, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic; jDepartment Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, University of Bern, Bern, Switzerland; kDepartment of Gynecology and Obstetrics, Herlev University Hospital, Copenhagen, Denmark; lDepartment of Obstetrics & Gynecology, Mater Dei Hospital, Msida, Malta; mNew York University School of Medicine, New York, NY, USA; nFederación Mexicana de Colegios de GinecologÍa y Obstetricia (FEMECOG), Mexico, Mexico; oPalacios Institute of Women’s Health, Madrid, Spain

ABSTRACT

Research into non-hormonal, alternative therapies is necessary for women for whom menopausal hormone therapy is contraindicated or for women who do not wish to take hormones. This review focuses on one such non-hormonal option, namely, purified and specific cytoplasmic pollen extract, or PureCyToninVR . This extract has been evaluated in several preclinical and clinical studies, where it demonstrated its value as a safe and non-estrogenic alternative for menopause. This review presents the beneficial effects of PureCyToninVR in the treatment of menopausal symptoms (e.g. hot flushes) in healthy women, as well as in premenstrual syndrome. We discuss the mechanism of action of PureCyToninVR, an SSRI-‘like’ therapy. The lack of estrogenic effect demonstrated in preclinical studies suggests that PureCyToninVR may also be a suitable option for the management of menopausal symptoms in women with breast cancer.
Table 1. In vitro and in vivo analysis with purified and specific cytoplasmic pollen extract: PureCyTonin®.
Type of study Study Publication/report Type of measurement Main results
No estrogenic activity HPLC analysis Hellstrom et al. (2012) A detailed study of phytoestrogen composition No trace of phytoestrogens
Estrogenic activity with uterotrophic screening assay Hellstrom et al. (2012) Uterotrophic screening assay in juvenile Wistar rats No uterotrophic effect in vivo compared with estradiol/no estrogenic activity
Reporter gene assay in 293T cells. Cell proliferation in MCF7 cells Espié M., IMS World Congress – Poster (2014) Espié (2013) Transcriptional activation through the estrogen receptors ER a or ER b with an ERE-luc cotransfection Proliferation was determined by the MTT test No affinity for estrogen receptors ER a and ER b/no estrogenic activity No proliferation on breast cancer cell line
Proliferation and apoptosis MCF7 TD47 breast cancer cell line with PGRMC1 Comparison with estradiol (E2) and growth factors Seeger et al. (2017) MCF-7 and T47D cells were transfected with PGRMC1 Different concentrations of pollen extract alone and in combination with E2 or growth factor were tested Proliferation was determined using the MTT test Apoptosis was determined using the CDD ELISA kit PureCyTonin® was neutral in the cell lines alone or in combination with E2 or growth factors in terms of cell proliferation and cell apoptosis, both in cells transfected with PGRMC1 and in cells not transfected with PGRMC1
Potential interaction with tamoxifen Goldstein et al. (2015) Potential inhibition of CYPD26 enzyme at high concentrations in pooled liver microsome with quinidine as a control No inhibition of CYPD26 with PureCyToninVR 6.53–10% compared with quinidine, which inhibits 100%
Potential mode of action Selective serotonin reuptake inhibition, genomic study Appel et al., GREM 2020, 1. in press. Effects of PureCyTonin® on the uptake of [3H]-serotonin into rat cortical synaptosomes RNA sequencing profile in SH-SY5 Y cells Inhibition of the uptake of [3H]- serotonin into rat cortical synaptosomes in a dosedependent manner Neuropeptides and neurotransmitters genes are differentially modulated
Table 2. Clinical trials with Serelys® in menopause.
Type of clinical trial Author and year of publication Type of measurement Main results
Randomized double-blind placebo-controlled Winther et al. (2005) 64 women double blind placebo-controlled trial 3 months of treatment MRS, 15 Quality of life QoL parameters 15 QoL parameters Diary of AUB Blood samples for FSH, E2, TT, SHBG 65% of women responded, with a reduction in hot flushes compared with 38% in the placebo group (p<.006). 54 women were analyzed. The MRS evaluation revealed a 23% reduction in hot flushes with Serelys® compared with placebo after 2 months, and a 22% reduction after 3 months. Improvement in tiredness, dizziness, mood, libido, headache, irritability, mood swings, and sensitiveness) in the Serelys® group compared with baseline (p<.031) No changes in vaginal dryness parameter No AUB No change in blood levels of FSH, E2, TT, SHBG
Randomized placebocontrolled compared with MHT D’Alterio et al. (2015) 45 women randomly treated either with Serelys® or with estrogen/progestin therapy or with placebo for 6 months. Evaluation at day 0, day 60, and day 90. The reduction in the Kupperman index was used for evaluation Efficacy was slightly lower but similar to that of the estrogen/progestin therapy in peri and postmenopausal neurovegetative symptoms.
Open-label study Elia et al. (2008) 417 women in France treated for 3 months, questionnaire and VAS evaluation at day 0 and day 90 The frequency of hot flushes was reduced by 65% (intensity by 64%), sweating and perspiration by 66% (intensity by 67%), irritability by 54%, and fatigue by 51%.
Open-label study Druckman et al. (2015) 324 women. Analysis of efficacy and tolerance in perimenopausal and menopausal women. Evaluation at day 0 and day 90 through VAS. Improvement in QoL by 53–72%. Reduction of intensity of menopausal symptoms in peri and menopausal women. No differences observed for either group.
Open-label Study Paczkowski et al. (2018) Quality of life in 50 women and reduction in hot flushes were assessed in an open study with the Menopause Rating Scale (MRS) and Female Sexual Functioning Inventory (FSFI) at 3 visits Shows very good efficacy of the product with respect to elimination of vasomotor symptoms as early as after 4 weeks of treatment. This effect increased during the subsequent months of treatment.
Open-label study Fait et al. (2019) 104 women in the Czech Republic treated for 3 months and evaluated with the Menopause Rating Scale (MRS) at day 0, day 30, day 60, and day 90 Significant decrease in menopausal symptoms between the starting point of the study and after 12 weeks (p<.0001). Hot flushes were reduced by 48.5%, sleep disturbances by 50.1%, and depressive mood by 51.2%.

Conclusions

Serelys® is an effective and safe non-hormonal alternative for alleviating menopausal symptoms without increasing the risk of breast cancer in women in whom MHT is contraindicated or who do not wish to use hormones. Serelys® has proven to be safe and efficacious. It improves hot flushes, sleep disturbances, and nervousness in menopausal women. The beneficial effects are also observed in PMS. These findings seem to correlate with the effect of its main ingredient, PureCyTonin® , on inhibition of the reuptake of serotonin and other neurotransmitters. Current studies are being performed to fully determine the mode of action of PureCyTonin® .