Luteinizing hormone and the aging brain
Open accessAbstract
Fluctuations in luteinizing hormone (LH) release contribute to the development and maintenance of the reproductive system and become dysregulated during aging. Of note, increasing evidence supports extra-gonadal roles for LH within the CNS, particularly as it relates to cognition and plasticity in aging and age-related degenerative diseases such as Alzheimer's disease (AD). However, despite increasing evidence that supports a link between this hormone and CNS function, the mechanisms underlying LH action within the brain and how they influence cognition and plasticity during the lifespan is poorly understood and, in fact, often in conflict. This chapter aims to provide an up-to-date review of the literature addressing the role of LH signaling in the context of CNS aging and disease and put forward a unifying hypothesis that may explain currently conflicting theories regarding the role of LHCGR signaling in CNS function and dysfunction in aging and disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Elevated levels of circulating luteinizing hormone during the ageing process impair BDNF expression and synaptic plasticity.
“Moreover, elevated levels of circulating luteinizing hormone (LH) during ageing process impair BDNF expression and synaptic plasticity.362”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [362]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hearing loss and cognitive decline in older adults
Lin, F. R., Yaffe, K., Xia, J., Xue, Q.-L., Harris, T. B., Purchase-Helzner, E., Satterfield, S., Ayonayon, H. N., Ferrucci, L., Simonsick, E. M., et al. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.1868 · Cited by 4,017 · see citing works
Hayashi, Y., Shi, S.-H., Esteban, J. A., Piccini, A., Poncer, J.-C., & Malinow, R. (2000) · Science · doi:10.1126/science.287.5461.2262 · Cited by 1,524 · see citing works
Mechanisms of CaMKII action in long-term potentiation
Lisman, J., Yasuda, R., & Raghavachari, S. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3192 · Cited by 1,134 · see citing works
Current understanding of Alzheimer’s disease diagnosis and treatment
Weller, J., & Budson, A. (2018) · F1000Research · doi:10.12688/f1000research.14506.1 · Cited by 1,083 · see citing works
2014 Alzheimer's disease facts and figures
Alzheimer's Association (2014) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2014.02.001 · Cited by 1,032 · see citing works
García‐Segura, L. M., Azcoitia, Í., & DonCarlos, L. L. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00025-3 · Cited by 938 · see citing works
Impey, S., Obrietan, K. H., Wong, S. T., Poser, S., Yano, S., Wayman, G. A., Deloulme, J., Chan, G. C. ‐., & Storm, D. R. (1998) · Neuron · doi:10.1016/s0896-6273(00)80602-9 · Cited by 889 · see citing works
Lehman, M. N., Coolen, L. M., & Goodman, R. L. (2010) · Endocrinology · doi:10.1210/en.2010-0022 · Cited by 768 · see citing works
Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity
Hardingham, G. E., Arnold, F. J. L., & Bading, H. (2001) · Nature Neuroscience · doi:10.1038/85109 · Cited by 537 · see citing works
Leydig cell numbers, daily sperm production, and serum gonadotropin levels in aging men
NEAVES, W. B., JOHNSON, L., PORTER, J. C., PARKER, C. R., & PETTY, C. S. (1984) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-59-4-756 · Cited by 495 · see citing works
Sex and the development of Alzheimer's disease
Pike, C. J. (2016) · Journal of Neuroscience Research · doi:10.1002/jnr.23827 · Cited by 405 · see citing works
Male pheromone–stimulated neurogenesis in the adult female brain: possible role in mating behavior.
Mak, G. K., Enwere, E. K., Gregg, C., Pakarainen, T., POUTANEN, M. H., Huhtaniemi, I. T., & Weiss, S. (2007) · Nature Neuroscience · doi:10.1038/nn1928 · Cited by 314 · see citing works
Estrogen effects on the brain: Actions beyond the hypothalamus via novel mechanisms.
McEwen, B. S., Akama, K. T., Spencer-Segal, J. L., Milner, T. A., & Waters, E. M. (2012) · Behavioral Neuroscience · doi:10.1037/a0026708 · Cited by 302 · see citing works
Human chorionic gonadotropin in cancer
Stenman, U., Alfthan, H. V., & Hotakainen, K. (2004) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2004.05.008 · Cited by 294 · see citing works
Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain
Lei, Z. M., Rao, C. V., Környei, J., Licht, P., & Hiatt, E. S. (1993) · Endocrinology · doi:10.1210/endo.132.5.8477671 · Cited by 284 · see citing works
Hormonal profiles after the menopause.
Chakravarti, S., Collins, W. P., Forecast, J. D., Newton, R., Oram, D. H., & Studd, J. W. W. (1976) · BMJ · doi:10.1136/bmj.2.6039.784 · Cited by 272 · see citing works
Daniel, J. M., Hulst, J. L., & Berbling, J. L. (2005) · Endocrinology · doi:10.1210/en.2005-0998 · Cited by 263 · see citing works
Prekeris, R., & Terrian, D. M. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.7.1589 · Cited by 245 · see citing works
The Postmenopausal Ovary Is Not a Major Androgen-Producing Gland
Couzinet, B., Méduri, G., Lecce, M. G., Young, J., Brailly, S., Loosfelt, H., Milgröm, E., & SCHAISON, G. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.10.7900 · Cited by 210 · see citing works
Menopause and Hypothalamic-Pituitary Sensitivity to Estrogen
Weiss, G. (2004) · JAMA · doi:10.1001/jama.292.24.2991 · Cited by 189 · see citing works
Ohnishi, T., Matsuda, H., Tabira, T., Asada, T., & Uno, M. (2001) · PubMed Central · Cited by 185 · see citing works
Different patterns of gray matter atrophy in early- and late-onset Alzheimer’s disease
Möller, C., Vrenken, H., Jiskoot, L. C., Versteeg, A., Barkhof, F., Scheltens, P., & van der Flier, W. M. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.02.013 · Cited by 183 · see citing works
Surgical versus natural menopause: cognitive issues
Henderson, V. W., & Sherwin, B. B. (2007) · Menopause · doi:10.1097/gme.0b013e31803df49c · Cited by 154 · see citing works
Elevated Gonadotropin Levels in Patients With Alzheimer Disease
Short, R. A., O’Brien, P. C., Graff‐Radford, N. R., et al. (2001) · Mayo Clinic Proceedings · doi:10.4065/76.9.906 · Cited by 148 · see citing works
Elevated Gonadotropin Levels in Patients With Alzheimer Disease
Short, R. A., O’Brien, P. C., Graff‐Radford, N. R., et al. (2001) · Mayo Clinic Proceedings · doi:10.1016/s0025-6196(11)62109-5 · Cited by 128 · see citing works
Bowen, R., Smith, M. A., Harris, P. L. R., Kubat, Z., Martins, R., Castellani, R., Perry, G., & Atwood, C. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10452 · Cited by 127 · see citing works
Using longitudinal data to define the perimenopause by menstrual cycle characteristics
DUDLEY, E. C., Hopper, J. L., Taffe, J. R., Guthrie, J. R., Burger, H., & Dennerstein, L. (1998) · Climacteric · doi:10.3109/13697139809080677 · Cited by 123 · see citing works
Associations between gonadotropins, testosterone and β amyloid in men at risk of Alzheimer’s disease
Verdile, G., Laws, S. M., Henley, D., Ames, D. J., Bush, A. I., Ellis, K. A., Faux, N. G., Gupta, V. B., Li, Q., Masters, C. L., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.147 · Cited by 121 · see citing works
Lukacs, H., Hiatt, E. S., Lei, Z. M., & Rao, C. V. (1995) · Hormones and Behavior · doi:10.1006/hbeh.1995.1004 · Cited by 120 · see citing works
Structure, function and regulation of gonadotropin receptors – A perspective
Menon, K. M. J., & Menon, B. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.01.021 · Cited by 118 · see citing works
Increases in luteinizing hormone are associated with declines in cognitive performance
Casadesús, G., Milliken, E. L., Webber, K. M., Bowen, R. L., Lei, Z. M., Rao, C. V., Perry, G. L., Keri, R. A., & Smith, M. A. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.06.013 · Cited by 118 · see citing works
Self-citationGreendale, G. A., Derby, C. A., & Maki, P. M. (2011) · Obstetrics and Gynecology Clinics of North America · doi:10.1016/j.ogc.2011.05.007 · Cited by 114 · see citing works
Giachello, C. N., Fiumara, F., Giacomini, C., Corradi, A. M., Milanese, C., Ghirardi, M., Benfenati, F., & Montarolo, P. G. (2010) · Journal of Cell Science · doi:10.1242/jcs.056846 · Cited by 108 · see citing works
Testosterone and gonadotropin levels in men with dementia.
Hogervorst, E., Combrinck, M. I., & Smith, A. D. (2004) · PubMed · Cited by 107 · see citing works
Ovulation Involves the Luteinizing Hormone-Dependent Activation of Gq/11 in Granulosa Cells
Breen, S. M., Andric, N. L., Ping, T., Xie, F., Offermans, S., Gossen, J. A., & Ascoli, M. (2013) · Molecular Endocrinology · doi:10.1210/me.2013-1130 · Cited by 97 · see citing works
Physiology of Gnrh and Gonadotropin Secretion
Marques, P., Skorupskaite, K., George, J. T., & Anderson, R. A. (2015) · Cited by 95 · see citing works
Apaja, P. M., Harju, K., Aatsinki, J. T., Petäjä‐Repo, U. E., & Rajaniemi, H. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311395200 · Cited by 84 · see citing works
Hebert, A. E., & Dash, P. K. (2002) · Learning & Memory · doi:10.1101/lm.48502 · Cited by 82 · see citing works
Berry, A. S., Tomidokoro, Y., Ghiso, J. A., & Thornton, J. E. (2008) · Hormones and Behavior · doi:10.1016/j.yhbeh.2008.02.006 · Cited by 77 · see citing works
Nead, K. T., Sinha, S., & Nguyen, P. L. (2017) · Prostate Cancer and Prostatic Diseases · doi:10.1038/pcan.2017.10 · Cited by 73 · see citing works
Bukovský, A., Indrapichate, K., Fujiwara, H., et al. (2003) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-1-46 · Cited by 71 · see citing works
Bryan, K. J., Mudd, J. C., Richardson, S. L., Chang, J., Lee, H., Zhu, X., Smith, M. A., & Casadesús, G. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06502.x · Cited by 70 · see citing works
Self-citationBowen, R. L., Perry, G. L., Xiong, C., Smith, M. A., & Atwood, C. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-141626 · Cited by 69 · see citing works
Bohacek, J., & Daniel, J. M. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.10.010 · Cited by 69 · see citing works
Kleppisch, T., Voigt, V., Allmann, R., & Offermanns, S. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-14-04943.2001 · Cited by 68 · see citing works
Direct action of gonadotropin in brain integrates behavioral and reproductive functions
Yang, E.-J., Nasipak, B. T., & Kelley, D. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608391104 · Cited by 65 · see citing works
Gonadotropins and Cognition in Older Women
Rodrigues, M. A., Verdile, G., Foster, J. K., Hogervorst, E., Joesbury, K. A., Dhaliwal, S. S., Corder, E. H., Laws, S. M., Hone, E., Prince, R. L., et al. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-13304 · Cited by 62 · see citing works
Peegel, H., Randolph, J. F., MIDGLEY, A. R., et al. (1994) · Endocrinology · doi:10.1210/endo.135.3.8070346 · Cited by 57 · see citing works
Toth, P., Lukacs, H., Hiatt, E. S., et al. (1994) · Brain Research · doi:10.1016/0006-8993(94)90478-2 · Cited by 54 · see citing works
Palm, R. F., Chang, J., Blair, J., García‐Mesa, Y., Lee, H., Castellani, R. J., Smith, M. A., Zhu, X., & Casadesús, G. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12706 · Cited by 53 · see citing works
Self-citationLuteinizing hormone: Evidence for direct action in the CNS
Blair, J. A., Bhatta, S., McGee, H., & Casadesús, G. (2015) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.06.020 · Cited by 52 · see citing works
Self-citationVerdile, G., Yeap, B. B., Clarnette, R., Dhaliwal, S. S., Burkhardt, M. S., Chubb, S. A. P., Ruyck, K. D., Rodrigues, M. A., Mehta, P. D., Foster, J. K., et al. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14208 · Cited by 51 · see citing works
Recent progress in luteinizing hormone/human chorionic gonadotrophin hormone research
Rahman, N. A., & Rao, C. V. (2009) · Molecular Human Reproduction · doi:10.1093/molehr/gap067 · Cited by 50 · see citing works
Is the adrenal cortex a target for gonadotropins?
Bernichtein, S., Alevizaki, M. K., & Huhtaniemi, I. T. (2008) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2008.06.003 · Cited by 48 · see citing works
Alhader, A. A., Lei, Z. M., & Rao, C. V. (1997) · Biology of Reproduction · doi:10.1095/biolreprod56.2.501 · Cited by 47 · see citing works
You, S., Kim, H., Hsu, C.-C., et al. (2000) · Biology of Reproduction · doi:10.1095/biolreprod62.1.108 · Cited by 45 · see citing works
Banks, W. A., Kastin, A. J., Akerstrom, V. L., et al. (1993) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1993.264.5.e723 · Cited by 45 · see citing works
Passage of Radioactive Substances from CSF to Hypophysial Portal Blood1
Ondo, J. G., Mical, R. S., & Porter, J. C. (1972) · Endocrinology · doi:10.1210/endo-91-5-1239 · Cited by 44 · see citing works
Luteinizing hormone acts at the hippocampus to dampen spatial memory
Burnham, V. L., Sundby, C. S., Laman-Maharg, A., & Thornton, J. E. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.11.007 · Cited by 36 · see citing works
Effects of the LHRH antagonist Cetrorelix on affective and cognitive functions in rats
Telegdy, G., Adamik, Á., Tanaka, M., & Schally, A. V. (2009) · Regulatory Peptides · doi:10.1016/j.regpep.2009.08.005 · Cited by 35 · see citing works
Luteinizing hormone as a key player in the cognitive decline of Alzheimer's disease
Burnham, V. L., & Thornton, J. E. (2015) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.05.010 · Cited by 34 · see citing works
Barron, A. M., Verdile, G., Taddei, K., Bates, K. A., & Martins, R. N. (2010) · Endocrinology · doi:10.1210/en.2009-1168 · Cited by 34 · see citing works
Luteinizing Hormone Involvement in Aging Female Cognition: Not All Is Estrogen Loss
Bhatta, S., Blair, J. A., & Casadesús, G. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00544 · Cited by 32 · see citing works
Self-citationEffects of Luteinizing Hormone on Multiple-Unit Activity in the Rat Hippocampus
Gallo, R. V., Johnson, J., Kalra, S. P., et al. (2008) · Neuroendocrinology · doi:10.1159/000122046 · Cited by 30 · see citing works
Hypothalamic LH May Play a Role in Control of Pituitary LH Release
Emanuele, N. V., Oslapas, R., Connick, E., et al. (2008) · Neuroendocrinology · doi:10.1159/000123194 · Cited by 30 · see citing works
Bohm-Levine, N., Goldberg, A., Mariani, M. M., Frankfurt, M., & Thornton, J. E. (2019) · Hormones and Behavior · doi:10.1016/j.yhbeh.2019.104590 · Cited by 27 · see citing works
Lai, W., Li, X., Zhu, H., Zhu, X., Tan, H., Feng, P., Chen, L., & Luo, C. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.104535 · Cited by 27 · see citing works
Stefańska, A., Cembrowska, P., Kubacka, J., Kuligowska-Prusińska, M., & Sypniewska, G. (2019) · Disease Markers · doi:10.1155/2019/2384069 · Cited by 25 · see citing works
Saudargienė, A., Cobb, S., & Graham, B. P. (2014) · Hippocampus · doi:10.1002/hipo.22365 · Cited by 24 · see citing works
Wahjoepramono, E. J., Wijaya, L. K., Taddei, K., et al. (2011) · Neuroendocrinology · doi:10.1159/000330812 · Cited by 23 · see citing works
Odle, J., Jacobi, S. K., Boyd, R. D., Bauman, D. E., Anthony, R. V., Bazer, F. W., Lock, A. L., & Serazin, A. C. (2017) · Advances in Nutrition · doi:10.3945/an.116.013896 · Cited by 23 · see citing works
Wiącek, M., Hagner, W., & Zubrzycki, I. Z. (2010) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0b013e3181e7060b · Cited by 21 · see citing works
Blair, J. A., Bhatta, S., & Casadesús, G. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.02.002 · Cited by 21 · see citing works
Self-citationMovsas, T. Z., Weiner, R. L., Greenberg, M. B., et al. (2017) · Frontiers in Pediatrics · doi:10.3389/fped.2017.00232 · Cited by 20 · see citing works
Cerebrospinal fluid human chorionic gonadotropin levels in normal pregnancy and choriocarcinoma.
Rs, B., Osathanondh, R., Dp, G., et al. (1981) · PubMed · Cited by 16 · see citing works
Hippocampal Gαq/11 but not Gαo-coupled receptors are altered in aging
McQuail, J. A., Davis, K. N., Miller, F., Hampson, R. E., Deadwyler, S. A., Howlett, A. C., & Nicolle, M. M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.01.009 · Cited by 14 · see citing works
Yuan, L., Peng, C., Liu, B.-H., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071736 · Cited by 11 · see citing works
Glass, J. D., & McClusky, M. E. (1987) · Cellular and Molecular Life Sciences · doi:10.1007/bf01942846 · Cited by 8 · see citing works
Mariani, M. M., Mojziszek, K., Curley, E., & Thornton, J. E. (2019) · Hormones and Behavior · doi:10.1016/j.yhbeh.2019.104631 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165 · see citing works
- Authors
- Mey, M., Bhatta, S., & Casadesús, G.
- Affiliations
- Kent State University (US)
- Corresponding author
- Gemma Casadesús
- Venue
- Vitamins and Hormones
- Publisher
- Elsevier
- Published
- 2021
- Volume
- 115
- Pages
- 89-104
- ISSN
- 0083-6729 (ISSN-L)
- PMC
- PMC9853463
- OpenAlex
- W3135567993
- Cited by
- 17
- References
- 79
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 3 · 2023: 3
- FWCI
- 11.97
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Vitamins and hormones (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (RF1AG054654)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- luteinizing hormone, luteinizing hormone receptor, cognition, synaptic plasticity, Alzheimer's disease, age-related neurodegeneration
- MeSH terms
- Aging, Brain, Cognition, Humans, Luteinizing Hormone, Neuronal Plasticity, Receptors, LH, Signal Transduction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
