The DOI matches its Crossref record; 65 of the 66 references it cites were found in a registry or an index.
Physiology of hot flashes
Open accessAbstract
Hot flashes are the most common symptom of the climacteric, although prevalence estimates are lower in some rural and non-Western areas. The symptoms are characteristic of a heat-dissipation response and consist of sweating on the face, neck, and chest, as well as peripheral vasodilation. Although hot flashes clearly accompany the estrogen withdrawal at menopause, estrogen alone is not responsible since levels do not differ between symptomatic and asymptomatic women. Until recently it was thought that hot flashes were triggered by a sudden, downward resetting of the hypothalamic setpoint, since there was no evidence of increased core body temperature. Evidence obtained using a rapidly responding ingested telemetry pill indicates that the thermoneutral zone, within which sweating, peripheral vasodilation, and shivering do not occur, is virtually nonexistent in symptomatic women but normal (about 0.4 degrees C) in asymptomatic women. The results suggest that small temperature elevations preceding hot flashes acting within a reduced thermoneutral zone constitute the triggering mechanism. Central sympathetic activation is also elevated in symptomatic women which, in animal studies, reduces the thermoneutral zone. Clonidine reduces central sympathetic activation, widens the thermoneutral zone, and ameliorates hot flashes. Estrogen virtually eliminates hot flashes but its mechanism of action is not known.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Based on published norms,10–13 hot flashes were flagged if there was an increase in sternal skin conductance of at least 2 μmho within a 30 second period, with a 15-minute post-event lock-out. Each skin conductance track was evaluated by a trained expert, verifying that each skin conductance event matched published norms for vasomotor events.”
From Clinical hypnosis in the treatment of postmenopausal hot flashes (2013) · cites this paper as [13]
Experimental — accuracy not yet measuredIn the citing paper
“Hot flushes are characterized by a transient and intense sensation of heat accompanied by the activation of heat-loss effectors including skin vasodilatation, sweating, and cold-seeking behavior (Fig. 3) (Freedman, 2001; Kronenberg, 2010).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Freedman, 2001
In the citing paper
“Hot flushes can be triggered by a variety of stimuli including thermal (increased ambient temperature or hot beverages), chemical (caffeine or spicy food) or other (stress or anxiety) (Archer et al., 2011; Freedman, 2001).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Freedman, 2001
In the citing paper
“After a hot flush is triggered, the core temperature drops (Fig. 3) (Freedman, 2001; Kronenberg, 1990; Molnar, 1975), as expected with the activation of heat dissipation effectors.”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Freedman, 2001
In the citing paper
“Conversely, raising the ambient temperature increases the frequency of flushes in symptomatic postmenopausal women, and this feature has been used to stimulate flushes in a laboratory setting (Freedman, 2001).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Freedman, 2001
In the citing paper
“Using an ingestible thermometer (radio-telemetry pill), a very small increase in core temperature was detected before the onset of 65% to 76% of flushes (Fig. 3) (Freedman, 1998, 2001).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Freedman, 2001
In the citing paper
“In symptomatic postmenopausal women, exposure to a warm environment provokes hot flushes (Freedman, 2001; Freedman and Roehrs, 2006; Kronenberg and Barnard, 1992; Molnar, 1981).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Freedman, 2001
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Modulation of neurotransmitter release by presynaptic autoreceptors
Starke, K., Göthert, M., & Kilbinger, H. J. (1989) · Physiological Reviews · doi:10.1152/physrev.1989.69.3.864 · Cited by 927
Hot Flashes: Epidemiology and Physiology a
KRONENBERG, F. (1990) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1990.tb30316.x · Cited by 601
Yohimbine: a pharmacological probe for study of the alpha 2-adrenoreceptor.
Goldberg, M. R., & Robertson, D. (1983) · PubMed · Cited by 438
"Menopausal Symptoms" in Women of Various Ages
Neugarten, B. L., & Kraines, R. J. (1965) · Psychosomatic Medicine · doi:10.1097/00006842-196505000-00009 · Cited by 382
Murkies, A. L., Wilcox, G., & Davis, S. R. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.2.4577 · Cited by 355
Premature ovarian failure: an update
Anasti, J. N. (1998) · Fertility and Sterility · doi:10.1016/s0015-0282(98)00099-5 · Cited by 338
Frontiers in Biochemical and Pharmacological Research in Depression
Usdin, E. (1984) · Medical Entomology and Zoology · Cited by 278
Menopausal flushes: a neuroendocrine link with pulsatile luteinizing hormone secretion
Casper, R. F., Yen, S. S. C., & Wilkes, M. M. (1979) · Science · doi:10.1126/science.462193 · Cited by 267
Core body temperature and circadian rhythm of hot flashes in menopausal women
Freedman, R. R., Norton, D., Woodward, S., & Cornélissen, G. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.8.7629229 · Cited by 249
Self-citationBiochemical, metabolic, and vascular mechanisms in menopausal hot flashes
Freedman, R. R. (1998) · Fertility and Sterility · doi:10.1016/s0015-0282(98)00137-x · Cited by 232
Self-citation
Flagged first, then by citations
1 of the 66 references couldn’t be matched to a known paper.
Research works printed but not linked: 5
- 10.1210/jc.80.8.2354 · DOI · Paper page
- Hutton JD, 1978, Relation between plasma estrone and estradiol and climacteric symptoms, Lancet, 1, 671
- Insel PA, 1987, Physiologic and pharmacologic regulation of adrenergic receptors, 201
- Kenemans P, 1996, Practical HRT, Med Forum Int, 1
- Tang G, 1993, The modern management of the menopause, 47
Cited by
Sorted by citations
Items 301–369 of 369
Dumont, A., Bendris, N., Dewailly, D., Letombe, B., & Robin, G. (2017) · EMC - Ginecología-Obstetricia · doi:10.1016/s1283-081x(17)86883-1 · Cited by 1
Jackson, R., & Tran, A. R. (2022) · Cambridge University Press eBooks · doi:10.1017/9781108942751.030 · Cited by 1
Vasomotor Symptoms, Cardiovascular Risk and the Role of Physical Activity in Midlife Women
Nilsson, S. (2023) · Linköping University medical dissertations · doi:10.3384/9789180752619 · Cited by 1
Sleep disorders and menopausal symptoms: a Latin American perspective on postmenopausal health
Arteaga, E., Blümel, J. E., Vallejo, M. S., Salinas, C., Tserotas, K., Calle, A., Dextre, M., Elizalde-Cremonte, A., Espinoza, M. T., Escalante, C., et al. (2025) · Climacteric · doi:10.1080/13697137.2025.2537979 · Cited by 1
van der Sluijs, C. P. (2007) · Cited by 1
An Overview of the Extent and Nature of Menopause and Its Physiological Basis
van der Schouw, Y. T. (2013) · Humana Press eBooks · doi:10.1007/978-1-62703-373-2_1 · Cited by 1
Bioidentical hormones for women with hot flushes
Gaudard, A. M. I. S., da Silva, E. M., de Souza, S. S., Torloni, M. R., & Macedo, C. R. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010407 · Cited by 1
Nachtigall, L. E. (2014) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000000250 · Cited by 1
Genazzani, A. R., Gambacciani, M., Simoncini, T., & Schneider, H. P. G. (2003) · Gynecological Endocrinology · doi:10.1080/09513590312331290258 · Cited by 1
Hot Flash: Impact of Sex Steroid Replacement
Haimov‐Kochman, R., & Hochner‐Celnikier, D. (2004) · Elsevier eBooks · doi:10.1016/b0-12-475570-4/00622-3 · Cited by 1
Desvenlafaxine: A therapeutic option for treatment of menopausal hot flashes
Archer, D. F. (2010) · Maturitas · doi:10.1016/j.maturitas.2010.02.007 · Cited by 1
The Role of KNDy Neurons in Estrogen Modulation of LH Release, Body Weight, and Thermoregulation
Smith, M. A. (2012) · UA Campus Repository (The University of Arizona) · Cited by 1
La périménopause en 2007 : de la physiopathologie à la prise en charge thérapeutique
Robin, G., & Dewailly, D. (2007) · Médecine thérapeutique / Médecine de la reproduction, gynécologie et endocrinologie · doi:10.1684/mte.2007.0060 · Cited by 1
Kupferer, E. (2007) · Texas ScholarWorks (Texas Digital Library) · Cited by 1
Friedenthal, J., Naftolin, F. N., Nachtigall, L. E., & Goldstein, S. R. (2018) · doi:10.1002/9781119072980.ch15 · Cited by 1
Prostate Carcinoma and Hot Flashes
Vilar-González, S., & Pérez-Rozos, A. (2011) · InTech eBooks · doi:10.5772/26303
HOT FLASHES, BLOOD GLUCOSE AND DIABETIC POSTMENOPAUSAL WOMEN
Boorsma, J. (2008) · Open ULeth Scholarship (OPUS) (University of Lethbridge)
Borud, E. K. (2010) · NORA - Norwegian Open Research Archives
Sleep Related Movement Disorders : Association with Menopause and Pregnancy
Wesström, J. (2013) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Can we predict who will experience recurrent vasomotor symptoms after stopping hormone therapy?
Gracia, C. R., & Sondheimer, S. J. (2010) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0b013e3181c6abff
Association between Body Mass Index and Sweating in Menopausal Women
Amabebe, E., Osayande, S. I., Ozoene, J. O., & Ugwu, A. C. (2014) · Open Journal of Endocrine and Metabolic Diseases · doi:10.4236/ojemd.2014.43008
González, S. V., Puig, F. M., Martos, M. A., Sánchez, M. V. V., Capellán, M. D. M. S., & Martí, S. S. (2009) · Actas Urológicas Españolas · doi:10.1016/s0210-4806(09)74157-9
González, S. V., Puig, F. M., Sánchez, M. V. V., Capellán, M. D. M. S., Martos, M. A., & Martí, S. S. (2009) · Actas Urológicas Españolas · doi:10.1016/s0210-4806(09)74136-1
Women’s Experiences of Discontinuing Hormone Therapy: A Dissertation
Fischer, M. A. (2011) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/mvmr-2418
Menstrual cycles, vasomotor symptoms, hormone therapy and risk of cardiovascular disease
Herber-Gast, G.-C. M. (2010) · Utrecht University Repository (Utrecht University)
He, W., & Deng, W. (2005) · Clinical Trials · doi:10.1191/1740774505cn122oa
Evaluation and management of side effects of breast cancer treatment
Boekhout, A. H. (2011) · Utrecht University Repository (Utrecht University)
Culture and symptom reporting at menopause
Melby, M. K., Lock, M., & Kaufert, P. (2015)
Extrato de soja no tratamento dos sintomas vasomotores no período menopausal
Carbonel, A. A. F., Simões, R. G., Baracat, M. C. P., Haidar, M. A., Baracat, E. C., & Soares, J. M. (2012)
Best Practice & Research Clinical Obstetrics and Gynaecology
Bruce, D., & RYMER, J. M. (2009)
Pien, G. W., Phillips, B. A., & Collop, N. A. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-1703-7.10058-1
Ovarian Ablation in Breast Cancer Patients and the Possibility of Influencing Treatment Side Effects
Palácová, M. (2016) · Klinicka onkologie · doi:10.14735/amko20163s29
Padmapriya, S., & Latheef, F. (2017) · International Journal of Research in Ayurveda and Pharmacy · doi:10.7897/2277-4343.076252
Effects of Alternanthera sessilis extract on Tail Skin Temperature in Rats; A Preliminary study
Chamawan, P. (2016) · Thai Journal of Pharmaceutical Sciences (TJPS)
Rich, T. A. (2017) · International Journal of Complementary & Alternative Medicine · doi:10.15406/ijcam.2017.09.00301
Wright, C. L. (2009) · UA Campus Repository (The University of Arizona)
Renaissance der Hormontherapie
Mann, C., Rogenhofer, N. N., Mahner, S., & Thaler, C. (2017) · MMW - Fortschritte der Medizin · doi:10.1007/s15006-017-9705-3
Impact of Endocrine Disorders in the Elderly
Sunsundegui, P., Santesteban-Moriones, V., & Landecho, M. F. (2019) · Endocrinology · doi:10.1007/978-3-319-66362-3_14-1
Agomelatin in der Behandlung der perimenopausalen Depression
Kögel, K. (2015) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-11073
Magnusson, G., & Johansson, S. (2011) · Lund University Publications Student Papers (Lund University)
Impact of Endocrine Disorders in the Elderly
Sunsundegui, P., Santesteban-Moriones, V., & Landecho, M. F. (2020) · Endocrinology · doi:10.1007/978-3-319-68729-2_14
LIU, J. H., & Arredondo, F. (2013) · Springer eBooks · doi:10.1007/978-1-4614-6837-0_10
Hillard, T. (2010) · CRC Press eBooks · doi:10.3109/9781439807217-58
Sturdee, D. W. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.00033-7
(2011) · Elsevier eBooks · doi:10.1016/b978-0-7295-3908-1.10025-9
González, S. V., Puig, F. M., Martos, M. A., Sánchez, M. V. V., Capellán, M. D. M. S., & Martí, S. S. (2009) · Actas Urológicas Españolas · doi:10.4321/s0210-48062009000400001
Dumont, A., Bendris, N., Dewailly, D., Letombe, B., & Robin, G. (2019) · Elsevier eBooks · doi:10.1016/b978-2-294-75965-9.00024-6
González, S. V., Puig, F. M., Sánchez, M. V. V., Capellán, M. D. M. S., Martos, M. A., & Martí, S. S. (2009) · Actas Urológicas Españolas · doi:10.4321/s0210-48062009000300005
Carpenter, J. S., & Flockhart, D. A. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.9444
Sturdee, D. W. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803678-5.00279-4
Goyal, A., Gupta, P., & Sturdee, D. W. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-99967-0.00010-7
Clain, E., & Santoro, N. F. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95488-4.00110-8
Stute, P. (2025) · Springer eBooks · doi:10.1007/978-3-662-70494-3_4
Cui, Z., Xu, K., Li, N., Liu, T.-M., & Zhang, Z. (2025) · Journal of Visualized Experiments · doi:10.3791/68922
Progesterone for reproductive vitality and women’s healthy ageing
Prior, J. C., & Vitzthum, V. J. (2026) · Exploration of Endocrine and Metabolic Diseases · doi:10.37349/eemd.2026.101460
Awad, R., Ulitsa, N., & Ayalon, L. (2026) · Journal of Women & Aging · doi:10.1080/08952841.2026.2640610
Non-hormonal treatments for hot flashes in breast cancer patients: a narrative review
Ibrahim, F. A., Said, N. O. E., Shash, E., & Ateyya, H. (2026) · Future Journal of Pharmaceutical Sciences · doi:10.1186/s43094-026-00951-6
Approach to Hot Flashes: A Narrative Review
Nayan, A., Teja, S., Nareddy, S., Mahesh, K. V., Goyal, M., & Bansal, R. (2026) · Journal of Postgraduate Medicine Education and Research · doi:10.5005/jp-journals-10028-1760
Flushing: Neuroendocrine Mechanisms and a Structured Diagnostic Approach
García-Sáenz, M. R., Sosa, E., Ferreira‐Hermosillo, A., Ramírez-Renteria, C., López-Juárez, N., & Espinosa-Cárdenas, E. (2026) · Clinical Endocrinology · doi:10.1111/cen.70157
Cui, J., Wei, X., Bin, L., Sun, S., Liu, Y., Yang, T., Liu, Z., & Wu, J. (2026) · Precision Medical Sciences · doi:10.1002/prm2.70039
Jamal, S., Elsabagh, A., Wani, L., & Issa, M. H. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1833603
Hypoglycemic Flash as a potential shared metabolic trigger for episodic autonomic disorders
Shigeto, M. (2026) · Medical Hypotheses · doi:10.1016/j.mehy.2026.112124
Lee, S. H., Jung, S., Won, G. H., Kim, J., Jung, S., Yeom, C., Lee, K., Son, K., Kim, J., Jeon, S. Y., et al. (2026) · Chronobiology International · doi:10.1080/07420528.2026.2723196
Reduced menopausal symptom severity in women with epilepsy: a multicenter case-control study
Erdoğan, Ş., Ziroğlu, Z., Gencer, E., Erdal, A., Koçak, Z. B., Güler, S. K., & Şener, Ö. (2026) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2026.111279
Bimpa, K., Emmanouil, V., Xydias, E. M., Varvaras, D., & Tsakos, E. (2026) · Cureus · doi:10.7759/cureus.117665
(2026) · Obstetrics and Gynecology · doi:10.1097/aog.0000000000006428
Metadata
- Authors
- Freedman, R. R.
- Affiliations
- Wayne State University (US)
- Corresponding author
- Freedman, Robert R.
- Venue
- American Journal of Human Biology
- Publisher
- Wiley
- Published
- 2001-05-31
- Volume
- 13
- Issue
- 4
- Pages
- 453-464
- ISSN
- 1042-0533 (ISSN-L)
- 1520-6300
- OpenAlex
- W2062202632
- Cited by
- 369
- References
- 66
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 3 · 2023: 8 · 2022: 10 · 2021: 5 · 2020: 10 · 2019: 14 · 2018: 13 · 2017: 12 · 2016: 22 · 2015: 10 · 2014: 16 · 2013: 24 · 2012: 9
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Human Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG-05233)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Physiology (medical) › Thermoregulation and physiological responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- hot flashes, climacteric, menopause, thermoneutral zone, heat dissipation, sweating, peripheral vasodilation, clonidine, estrogen, core body temperature
- MeSH terms
- Body Temperature Regulation, Circadian Rhythm, Clonidine, Female, Humans, Menopause, Middle Aged, Risk Factors, Skin Temperature, Sweating, Sympatholytics, Time Factors, Estrogen Replacement Therapy, Hot Flashes
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
