{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T09:23:01Z","timestamp":1787304181373,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shionogi SRL"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: The menopausal transition may be accompanied by several disabling symptoms which impair quality of life. Many women cannot proceed with and\/or refuse hormonal replacement therapy (HRT) and, thus, they rely on non-hormonal remedies to manage climacteric syndrome. Methods: This was a retrospective study analyzing the impact of a combination of Purified Cytoplasm of Pollen (PCP) with vitamin D (vitD) and vitamin K2 (vitK2) on menopausal symptoms and bone parameters in a sample of symptomatic women (Group A, n = 22) compared to controls (Group B, n = 23). Results: We found that blood levels of vitD (25OHD) significantly increased within Group A (p = 0.0004) whereas no significance was reached within Group B (p &gt; 0.05) after a three-month therapy. Compared with the baseline, serum C-terminal telopeptide of type I collagen (CTX) turned out to be significantly reduced within Group A (p = 0.0415) but not within Group B (p &gt; 0.05). Comparing Group A and Group B, the values of CTX significantly differed after treatment (p = 0.0458). In comparison to the baseline, significant differences emerged within Group A for physical, psychosocial, and vasomotor domains of Menopause-Specific Quality of Life (MenQol) (p &lt; 0.05) whereas no significant difference was found for the sexual domain (p &gt; 0.05). Comparing Group A and Group B, significant differences were observed for all MenQol domains (p &lt; 0.05), except for the sexual domain (p &gt; 0.05) after therapy. Conclusions: Based on our findings, the combination of PCP, vitD, and vitK2 could be used for managing vasomotor and mood disturbances associated with menopause, whilst also offering the added benefit of maintaining bone health.<\/jats:p>","DOI":"10.3390\/nu18162734","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T08:14:01Z","timestamp":1787300041000},"page":"2734","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beneficial Effects of Purified Cytoplasm of Pollen Associated with Vitamin D and Vitamin K2 on Menopausal Symptoms and Bone Health"],"prefix":"10.3390","volume":"18","author":[{"given":"Anna","family":"Capozzi","sequence":"first","affiliation":[{"name":"Department of Women, Child and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-335X","authenticated-orcid":false,"given":"Anna","family":"Fagotti","sequence":"additional","affiliation":[{"name":"Department of Women, Child and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Sacco","sequence":"additional","affiliation":[{"name":"Dipartimento Interdisciplinare di Medicina (DIM), Universit\u00e0 Degli Studi di Bari Aldo Moro, 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pasi","sequence":"additional","affiliation":[{"name":"Polistudio Donna si Cura, 48124 Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Mellino","sequence":"additional","affiliation":[{"name":"Poliambulatorio Polispecialistico Domus Mulieris, 01100 Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1616-9105","authenticated-orcid":false,"given":"Stefano","family":"Lello","sequence":"additional","affiliation":[{"name":"Department of Women, Child and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.maturitas.2021.03.007","article-title":"What women think about menopause: An Italian survey","volume":"147","author":"Vaccaro","year":"2021","journal-title":"Maturitas"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1097\/gme.0b013e318185e25b","article-title":"Vasomotor symptoms are associated with a lower bone mineral density","volume":"16","author":"Gast","year":"2009","journal-title":"Menopause"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"The NAMS 2017 Hormone Therapy Position Statement Advisory Panel (2017). The 2017 hormone therapy position statement of The North American Menopause Society. Menopause, 24, 728\u2013753.","DOI":"10.1097\/GME.0000000000000921"},{"key":"ref_4","first-page":"395","article-title":"Executive Committee of the Italian Society of Menopause (SIM) and of the Italian Society of Gynaecology of the Third Age (SIGiTE). Recommendations on menopausal hormone replacement therapy","volume":"71","author":"Cagnacci","year":"2019","journal-title":"Minerva Ginecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1097\/GME.0000000000002200","article-title":"The 2023 nonhormonal therapy position statement of The North American Menopause Society","volume":"30","author":"Shufelt","year":"2023","journal-title":"Menopause"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"214","DOI":"10.36129\/jog.33.04.01","article-title":"Phytotherapy for menopausal symptoms: Recommendations of the Italian menopause society (SIM) and the Italian society of gynaecology for the third age (SIGiTE)","volume":"33","author":"Cagnacci","year":"2021","journal-title":"Ital. J. Gynaecol. Obstet."},{"key":"ref_7","first-page":"153","article-title":"Role of Alternate Therapies to Improve the Quality of Life in Menopausal Women: A Systematic Review","volume":"14","author":"Aarshageetha","year":"2023","journal-title":"J. Midlife Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.maturitas.2011.11.002","article-title":"EMAS position statement: Vitamin D and postmenopausal health","volume":"71","author":"Brincat","year":"2012","journal-title":"Maturitas"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nuti, R., Gennari, L., Cavati, G., Caffarelli, C., Frediani, B., Gonnelli, S., Laurentaci, C., Mauro, G.L., Malavolta, N., and Minisola, G. (2025). Vitamin D intake in Italian healthy subjects and patients with different pathological disorders. Front. Nutr., 20, Erratum in Front. Nutr. 2025, 17, 1756282. https:\/\/doi.org\/10.3389\/fnut.2025.1756282.","DOI":"10.3389\/fnut.2025.1672798"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/ajcn\/76.1.187","article-title":"Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: Third National Health and Nutrition Examination Survey, 1988\u20131994","volume":"76","author":"Scanlon","year":"2002","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline","volume":"96","author":"Holick","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0378-5122(96)01038-9","article-title":"A menopause specific quality of life questionnaire: Development and psychometric properties","volume":"24","author":"Hilditch","year":"1996","journal-title":"Maturitas"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-3-032-04357-3_6","article-title":"Vitamin D and Mineral Ion Regulation","volume":"1493","author":"Ahmed","year":"2026","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wimalawansa, S.J., Weiss, S.T., and Hollis, B.W. (2024). Integrating Endocrine, Genomic, and Extra-Skeletal Benefits of Vitamin D into National and Regional Clinical Guidelines. Nutrients, 16.","DOI":"10.3390\/nu16223969"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"895","DOI":"10.2174\/1871530319666190204165207","article-title":"Biomarkers of Osteoporosis: An Update","volume":"19","author":"Parveen","year":"2019","journal-title":"Endocr. Metab. Immune Disord.-Drug Targets"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e081250","DOI":"10.1136\/bmj-2024-081250","article-title":"Advances in the management of osteoporosis","volume":"390","author":"Hoong","year":"2025","journal-title":"BMJ"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s00198-025-07422-3","article-title":"Update on the role of bone turnover markers in the diagnosis and management of osteoporosis: A consensus paper from The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), International Osteoporosis Foundation (IOF), and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)","volume":"36","author":"Bhattoa","year":"2025","journal-title":"Osteoporos. Int."},{"key":"ref_18","first-page":"2","article-title":"Der Stellenwert der Knochenumbauparameter im Management der Osteoporose [The importance of bone remodelling parameters in the management of osteoporosis]","volume":"82","author":"Meier","year":"2025","journal-title":"Ther. Umsch."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Elahmer, N.R., Wong, S.K., Mohamed, N., Alias, E., Chin, K.Y., and Muhammad, N. (2024). Mechanistic Insights and Therapeutic Strategies in Osteoporosis: A Comprehensive Review. Biomedicines, 12.","DOI":"10.3390\/biomedicines12081635"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/09513590.2019.1689554","article-title":"Role of vitamin K2 in bone metabolism: A point of view and a short reappraisal of the literature","volume":"36","author":"Capozzi","year":"2020","journal-title":"Gynecol. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jadhav, N., Ajgaonkar, S., Saha, P., Gurav, P., Pandey, A., Basudkar, V., Gada, Y., Panda, S., Jadhav, S., and Mehta, D. (2022). Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.896920"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/cen.13076","article-title":"Cortisol dysregulation is associated with daily diary-reported hot flashes among midlife women","volume":"85","author":"Gibson","year":"2016","journal-title":"Clin. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1111\/cen.12995","article-title":"Daily salivary cortisol patterns in midlife women with hot flashes","volume":"84","author":"Reed","year":"2016","journal-title":"Clin. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1080\/09513590.2020.1722994","article-title":"Purified and specific cytoplasmic pollen extract: A non-hormonal alternative for the treatment of menopausal symptoms","volume":"36","author":"Genazzani","year":"2020","journal-title":"Gynecol. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"516","DOI":"10.23736\/S2724-606X.21.04964-2","article-title":"The benefits of purified cytoplasm of pollen in reducing menopausal symptoms in peri- and post-menopause: An Italian multicenter prospective observational study","volume":"74","author":"Lello","year":"2022","journal-title":"Minerva Obstet. Gynecol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4509","DOI":"10.2174\/1381612826666200721002022","article-title":"Non-hormonal Treatments for Menopausal Symptoms and Sleep Disturbances: A Comparison Between Purified Pollen Extracts and Soy Isoflavones","volume":"26","author":"Conte","year":"2020","journal-title":"Curr. Pharm. Des."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2162035","DOI":"10.1080\/09513590.2022.2162035","article-title":"Vasomotor symptoms and management of women undergoing treatment for breast cancer: Literature review with focus on the therapeutic potential of cytoplasmic pollen extract","volume":"39","author":"Lello","year":"2023","journal-title":"Gynecol. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2334796","DOI":"10.1080\/09513590.2024.2334796","article-title":"A prospective, multicenter, randomized, double-blind placebo-controlled trial on purified and specific Cytoplasmic pollen extract for hot flashes in breast cancer survivors","volume":"40","author":"Bounous","year":"2024","journal-title":"Gynecol. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2566993","DOI":"10.1080\/09513590.2025.2566993","article-title":"The in vitro effects of purified and specific cytoplasmic pollen extract on dopaminergic and GABAergic systems","volume":"41","author":"Appel","year":"2025","journal-title":"Gynecol. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1080\/13697130500117987","article-title":"Femal, a herbal remedy made from pollen extracts, reduces hot flushes and improves quality of life in menopausal women: A randomized, placebo-controlled, parallel study","volume":"8","author":"Winther","year":"2005","journal-title":"Climacteric"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/MED.0000000000000938","article-title":"Approach to premenopausal osteoporosis","volume":"32","author":"Agarwal","year":"2025","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3780","DOI":"10.1210\/jc.2006-0544","article-title":"Low bone mineral density in the early menopausal transition: Role for ovulatory function","volume":"91","author":"Grewal","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1097\/GME.0000000000002301","article-title":"The efficacy of purified pollen extract for reducing vasomotor symptoms in women: A systematic review and meta-analysis","volume":"31","author":"Acquarulo","year":"2024","journal-title":"Menopause"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/16\/2734\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T08:23:22Z","timestamp":1787300602000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/16\/2734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":33,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["nu18162734"],"URL":"https:\/\/doi.org\/10.3390\/nu18162734","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]}}}