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Progesterone therapy in women with complex partial and secondary generalized seizures
Abstract
This open trial assessed the effects of adjunctive progesterone therapy on seizure frequency in 25 women with catamenial exacerbation of complex partial (CPS) and secondary generalized motor (SGMS) seizures. Progesterone was well tolerated by 23 of the 25 women and had readily reversible dose-related side effects of asthenia and emotional depression in two. Eighteen women (72%) experienced a decline in seizure frequency during a 3-month treatment period compared with the 3 months prior to therapy (p < 0.01). Average daily CPS frequency declined by 54% (p < 0.01), SGMS by 58% (p < 0.02).
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“while clinical trials have also been conducted with progesterone, the synthetic progestin norethisterone, and the gonadotropin antagonist goserelin [54,147].”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [54]
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Items 101–200 of 202
A Treatment Approach to Catamenial Epilepsy
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To what extent do premenstrual and interictal dysphoric disorder overlap? Significance for therapy.
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Self-citationProgesterone therapy in women with epilepsy
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“So far, Herzog has had the most numerous group of epileptic patients treated with progesterone, which included 25 individuals [15].”
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Castration in female rats modifies the development of the pilocarpine model of epilepsy.
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“Reproductive hormones are known to modulate neuronal excitability by specific mechanisms that alter the cellular metabolism and neural transmission (Herzog, 1995; Smith, 1989).”
BackgroundHerzog, A., Friedman, M. N., Freund, S., & Pascual-Leone, Á. (2001) · Epilepsy & Behavior · doi:10.1006/ebeh.2001.0232 · Cited by 26
Self-citationA Clinical Approach to Catamenial Epilepsy: A Review.
Frank, S., & Tyson, N. (2020) · The Permanente Journal · doi:10.7812/tpp/19.145 · Cited by 25
“A small earlier study on 25 patients with C1 and C3 pattern using cyclic natural progesterone treatment resulted in 72% of the subjects having reduced seizure activity, which persisted at a 3-year follow-up study.(35,36) In addition, a randomized study of 38 women with C1 or C3 seizures found that the number of seizur…”
BackgroundProgesterone therapy in women with intractable catamenial epilepsy
Najafi, M. R., Sadeghi, M., Mehvari, J., Zare, M., & Akbari, M. (2013) · Advanced Biomedical Research · doi:10.4103/2277-9175.107974 · Cited by 25
“[31‐33] In a study conducted in women with catamenial epilepsy, 100 to 200 mg of progesterone has been used as the adjuvant treatment during the 15th to 28th days of the menstruation and it was revealed that there has been a monthly decrease of 54% to 68% in the number of the seizures in 72% of the patients under a 3‐…”
Catamenial epilepsy: hormonal aspects
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“In the seminal study, Herzog et al. [5] defined catamenial epilepsy as a greater than average seizure frequency during perimenstrual or periovulatory periods in normal ovulatory cycles and during the luteal phase in anovulatory cycles.”
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Self-citationNeurosteroids – From Basic Research to Clinical Perspectives
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“Similarly, a 1995 study by Herzog [ 22 ] evaluated 25 women with temporal lobe epilepsy and a diagnosis of catamenial epilepsy treated with progesterone lozenges.”
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Cutia, C. A., & Christian-Hinman, C. A. (2023) · Frontiers in neuroendocrinology (Print) · doi:10.1016/j.yfrne.2023.101084 · Cited by 17
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“P has anticonvulsant activity (Herzog, 1995; Herzog et al., 1997; Reddy et al., 2001; Reddy, 2010; Herzog et al., 2012).”
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Pereira, M., Soares, J. M., Valente, S., Oliveira, P., Cavalheiro, E., Amado, D., & Baracat, E. (2009) · Maturitas · doi:10.1016/j.maturitas.2008.10.014 · Cited by 16
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Foldvary, N. (2001) · Neurologic clinics · doi:10.1016/s0733-8619(05)70024-4 · Cited by 15
Fibromyalgia pathogenesis explained by a neuroendocrine multistable model
Demori, I., Losacco, S., Giordano, G., Mucci, V., Blanchini, F., & Burlando, B. (2024) · PLOS ONE · doi:10.1371/journal.pone.0303573 · Cited by 14
Reddy, D., Venkatarangan, L., Chien, B., & Ramu, K. (2005) · Steroids · doi:10.1016/j.steroids.2005.05.007 · Cited by 14
Ketogenic diet decreases circulating concentrations of neuroactive steroids of female rats.
Rhodes, M. E., Talluri, J., Harney, J., & Frye, C. (2005) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2005.05.025 · Cited by 14
“Progesterone has also demonstrated clinical benefits in women with catamenial epilepsy [28,29].”
BackgroundEpilepsy in adolescents: hormonal considerations.
Logsdon-Pokorny, V. K. (2000) · Journal of Pediatric and Adolescent Gynecology · doi:10.1016/s1083-3188(99)00036-4 · Cited by 14
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Reddy, D. (2007) · Women's Health · doi:10.2217/17455057.3.2.195 · Cited by 13
“Average monthly seizure frequency was reportedly reduced by 54–68% during the 3-month treatment period [44].”
BackgroundWomen's issues in epilepsy. Menses, childbearing, and more.
Liporace, J. (1997) · Postgraduate medicine · doi:10.3810/pgm.1997.07.253 · Cited by 13
The effect of labor on sevoflurane requirements during cesarean delivery.
Erden, V., Erkalp, K., Yangin, Z., Delatioğlu, H., Kiroglu, S., Ortaküz, S., & Ozdemir, B. (2011) · International journal of obstetric anesthesia · doi:10.1016/j.ijoa.2010.08.008 · Cited by 13
“On administration, these steroids exhibit clear behavioral effects that include anxiolysis, sedation, and analgesia, as well as anticonvulsant and general anesthetic-like properties (in large doses).(20,21) These depressant and hypnotic effects of progesterone appear to influence the anesthetic requirement in pregnant…”
BackgroundZajda, M., Krza̧ścik, P., Hill, M., & Majewska, M. D. (2012) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2012-1881 · Cited by 12
“…modulate anxiety, affect sleep and activity phases, and influence learning and memory (for example: Bäckström et al. 1984, Mendelson et al. 1987, Herzog 1995, Kokate et al. 1996, Edgar et al. 1997, Lancel et al. 1997, Czlonkowska et al. 2001, Damianisch et al. 2001, Huppert and van Niekerk…”
BackgroundSpecial Considerations in the Management of Women with Epilepsy in Reproductive Years
Parekh, K., Kravets, H. D., & Spiegel, R. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12010088 · Cited by 10
Stefanidou, M., & Montouris, G. (2020) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2020.100855 · Cited by 10
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Opaleke, A., & Helmers, S. (2007) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2007.08.005 · Cited by 10
Hemispheric mediation of spatial attention: Pseudoneglect after callosal stroke
Wolk, D., & Coslett, H. (2004) · Annals of Neurology · doi:10.1002/ana.20213 · Cited by 10
Withdrawal Effects of a Neuroactive Steroid as a Model of PMS: Synaptic Physiology to Behavior
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Herson, P. S., & Hurn, P. D. (2010) · Progress in brain research · doi:10.1016/b978-0-444-53630-3.00012-9 · Cited by 28
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Self-citationProgesterone and its derivatives for the treatment of catamenial epilepsy: A systematic review.
Nucera, B., Rinaldi, F., Dono, F., Lanzone, J., Evangelista, G., Consoli, S., Tappatà, M., Narducci, F., Troisi, S., Trinka, E., et al. (2023) · Seizure · doi:10.1016/j.seizure.2023.05.004 · Cited by 9
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Lundberg, P. (1997) · Cephalalgia · doi:10.1177/0333102497017s2013 · Cited by 9
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A case of recurrent status epilepticus and successful management with progesterone.
Ramanujam, B., Arora, A., Malhotra, V., Dash, D., Mehta, S., & Tripathi, M. (2016) · Epileptic disorders · doi:10.1684/epd.2016.0792 · Cited by 8
Oxcarbazepine and Carbamazepine: Expected and Unexpected Differences and Similarities
Abou-Khalil, B. W. (2007) · Epiliepsy currents/Epilepsy currents · doi:10.1111/j.1535-7511.2007.00176.x · Cited by 11
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“01).(5) The averagedaily complex partial seizure frequency declinedby 54% (P<.”
BackgroundA Possible Role of the Thalamus in Some Cases of Sudden Unexpected Death in Epilepsy
Scorza, F., Sander, J. W., Cendes, F., Arida, R., & Cavalheiro, E. (2007) · Epilepsia · doi:10.1111/j.1528-1167.2007.01009_9.x · Cited by 6
“…metabolites, such as allopregnanolone, which have anticonvulsant activity in animal models by acting as positive allosteric modulators at the GABAA receptor (Kokate et al., 1994; Herzog, 1995; Reddy, Epilepsia, Vol. 48, No. 5, 2007 2001; Lonsdale and Burnham, 2003; Scharfman and MacLusky, 2006).”
The neuroendocrine puzzle of epilepsy and infertility: what are we missing?
Kobylarek, D., Zakryś, K., Gierszewska, J., Pagidela, B. R., Lan, Y.-Y., Kovinthapillai, R., Rajczewski, A., Kozubski, W., & Michalak, S. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1658284 · Cited by 5
A Comprehensive Review on the Influence of Menstrual Cycle and Pregnancy on Epileptic Seizures
Kolomar, H., Osman, A., Blanco, L. V. A., Alotaibi, F. A., del Valle, I. L. F., Mohammed, S. F., Singh, S., Algitagi, F. M. F., & León, E. M. (2025) · Cureus · doi:10.7759/cureus.80387
Catamenial epilepsy: current concepts of definition, prevalence, pathophysiology and treatment
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“1 Investigational SexHormone Treatments ofwomenwith epilepsy Investigational Treatments Dosage Potential Adverse Effects Progesterone Lozenges Days 14–25: ½–1 lozenge tid Days 26–27: ¼–½ lozenge tid Day 28: ¼ lozenge tid Sedation, depression, breast tenderness, vaginal bleeding, constipation, exacerbation of asthma, w…”
InfluentialSelf-citationNonconvulsive Seizures in the Pediatric Intensive Care Unit: Out of Sight, Out of Mind?
Garcia, P. (2007) · Epilepsy Currents · doi:10.1111/j.1535-7511.2007.00173.x · Cited by 4
Treatment Options for Hypothalamic Hamartomas—No Laughing Matter
Schwartz, T. (2007) · Epilepsy Currents · doi:10.1111/j.1535-7511.2007.00175.x · Cited by 4
Yamamoto, A., Ide, S., Honzawa, S., Masuyama, T., Iwasaki, Y., & Kaga, M. (2014) · Journal of Nursing & Care · doi:10.4172/2167-1168.1000197 · Cited by 3
“The fluctuations in concentration of antiepileptic drug (AED) and changes in water and electrolyte balance are also thought to be the causes of catamenial epilepsy [6-14].”
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Self-citationWhite matter microstructural changes across the menstrual cycle: a differential tractography study
Porcu, M., Cocco, L., Pasquini, L., Suri, J. S., Marrosu, F., & Saba, L. (2025) · Neuroradiology · doi:10.1007/s00234-025-03662-6 · Cited by 2
Female ovarian steroids in epilepsy: A cause or remedy
Alam, M. N., Ahmad, A., Al-Abbasi, F., & Ahmad, A. (2013) · Pharmacological Reports · doi:10.1016/s1734-1140(13)71061-2 · Cited by 2
“Accordingly, progesterone achieved its reputation of having antiseizure activity in a variety of animal models of epilepsy a long time ago [7, 16, 35, 36, 39, 49, 56].”
BackgroundTreatment of Catamenial Epilepsy is Still up in the Air
French, J. (2013) · Epilepsy Currents · doi:10.5698/1535-7597-13.2.71 · Cited by 2
“In itself, this is yet another example of why randomized controlled trials are so important; previous open trials had demonstrated a > 50 % overall reduction in seizures compared to pretreatment baseline, a result that was clearly not supported (3, 4).”
ResultDisease, transplantation and regeneration
(1996) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(96)80108-5 · Cited by 2
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Klein, P., & Janoušek, J. (2010) · Epilepsy · doi:10.1201/9781420085594-c27
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“An alternative and possibly unifying consideration is that PCOS may develop as an interactional effect between AED use and epilepsy (Herzog, 1996; Herzog and Schachter, 2001).”
Self-citationMore is Not Better: Hormones for Menopausal Women with Epilepsy?
Pennell, P. (2007) · Epilepsy Currents · doi:10.1111/j.1535-7511.2007.00172.x · Cited by 1
Hormone Replacement Therapy in Women with Epilepsy
Hussain, H. M., & Perucca, E. (2007) · Epilepsia · doi:10.1111/j.1528-1167.2007.01009_2.x · Cited by 2
“…metabolites, such as allopregnanolone, which have anticonvulsant activity in animal models by acting as positive allosteric modulators at the GABAA receptor (Kokate et al., 1994; Herzog, 1995; Reddy, Epilepsia, Vol. 48, No. 5, 2007 2001; Lonsdale and Burnham, 2003; Scharfman and MacLusky, 2006).”
Response to Hussain and Perucca
Scharfman, H., & MacLusky, N. J. (2007) · doi:10.1111/j.1528-1167.2007.01009_3.x · Cited by 1
“…metabolites, such as allopregnanolone, which have anticonvulsant activity in animal models by acting as positive allosteric modulators at the GABAA receptor (Kokate et al., 1994; Herzog, 1995; Reddy, Epilepsia, Vol. 48, No. 5, 2007 2001; Lonsdale and Burnham, 2003; Scharfman and MacLusky, 2006).”
Psychiatric Disorders in Juvenile Myoclonic Epilepsy
Gélisse, P., Thomas, P., Samuelian, J., & Gentin, P. (2007) · Epilepsia · doi:10.1111/j.1528-1167.2007.01009_4.x · Cited by 1
“…metabolites, such as allopregnanolone, which have anticonvulsant activity in animal models by acting as positive allosteric modulators at the GABAA receptor (Kokate et al., 1994; Herzog, 1995; Reddy, Epilepsia, Vol. 48, No. 5, 2007 2001; Lonsdale and Burnham, 2003; Scharfman and MacLusky, 2006).”
Reproductive Hormones in Epilepsy Therapy: From Old Promises to New Hopes
Verrotti, A., Prezioso, G., D’Egidio, C., & Belcastro, V. (2015) · doi:10.1007/978-3-319-12283-0_11 · Cited by 1
Botanicals and Nutrition in the Treatment of Epilepsy
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Novel Effects of Neuroactive Steroids in the Central Nervous System
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Noe, K. H. (2020) · Epilepsy · doi:10.1007/978-3-030-59078-9_27
Bătrînu, M.-G., & Tero-Vescan, A. (2020) · Acta Medica Transilvanica · doi:10.2478/amtsb-2020-0007
“…studies performed by Herzog A. and other researchers demonstrated the effect of progesterone in the treatment of catamenial epilepsy, also linked with this mechanism (8,9,10) while ganaxolone is a neuroasteroid agent that has been evaluated in human clinical trials for the treatment of epilepsy.”
Penovich, P. (2019) · Understanding Epilepsy · doi:10.1017/9781108754200.021
CATAMENIAL EPILEPSY - UPDATE ON PRACTICAL MANAGEMENT
Lukić, S. (2018) · Acta Medica Medianae · doi:10.5633/amm.2018.0416
“Two small, open studies evaluated natural progesterone as add-on treatment in women with complex partial seizures (14, 15).”
BackgroundFemale Sex Hormones and Epilepsy
Chansakul, C. (2015) · doi:10.31524/bkkmedj.2015.09.013
Treatments for peri‐menstrual seizures
Li, Q.-F., Yang, M., He, L., Chen, Z., Wang, S.-R., Wang, T., Cai, M., & Zhou, D. (2015) · doi:10.1002/14651858.cd010086.pub2
Sandhu, M. A., & Anjum, M. S. (2013) · Journal of Steroids & Hormonal Science · doi:10.4172/2157-7536.s4-001
“With occurrence of catamenial epilepsy seizure there is a sudden decline in progesterone secretion during the premenstrual period [43] and the treatment with progestin is helpful [44].”
BackgroundReproductive health care for developmentally disabled adolescents
Quint, E., & Ernst, S. (2008) · doi:10.3109/9780203091784-24
Gender-Specific Challenges in the Management of Epilepsy in Women
Noe, K. H. (2007) · Seminars in Neurology · doi:10.1055/s-2007-985335
“Natural progesterone taken orally on a cyclical basis has also been shown effective in small numbers of women, with a 50% average decline in seizure frequency over a 3-year period.(12,13) If a decision is made to attempt hormonal therapy for seizure control, a gynecologic evaluation is generally recommended.”
BackgroundParasomnias Versus Epilepsy: Common Grounds and a Need to Change the Approach to the Problem
Tinuper, P. (2007) · Epilepsia · doi:10.1111/j.1528-1167.2007.01009_5.x
“…metabolites, such as allopregnanolone, which have anticonvulsant activity in animal models by acting as positive allosteric modulators at the GABAA receptor (Kokate et al., 1994; Herzog, 1995; Reddy, Epilepsia, Vol. 48, No. 5, 2007 2001; Lonsdale and Burnham, 2003; Scharfman and MacLusky, 2006).”
“…metabolites, such as allopregnanolone, which have anticonvulsant activity in animal models by acting as positive allosteric modulators at the GABAA receptor (Kokate et al., 1994; Herzog, 1995; Reddy, Epilepsia, Vol. 48, No. 5, 2007 2001; Lonsdale and Burnham, 2003; Scharfman and MacLusky, 2006).”
Derry, C., Duncan, J. S., & Berkovic, S. (2007) · doi:10.1111/j.1528-1167.2007.01009_6.x
“…metabolites, such as allopregnanolone, which have anticonvulsant activity in animal models by acting as positive allosteric modulators at the GABAA receptor (Kokate et al., 1994; Herzog, 1995; Reddy, Epilepsia, Vol. 48, No. 5, 2007 2001; Lonsdale and Burnham, 2003; Scharfman and MacLusky, 2006).”
Hormonelle Zusatztherapie katamenialer Anfälle
Jadidzadeh, H., & Bauer, J. (2006) · Zeitschrift für Epileptologie · doi:10.1007/s10309-006-0187-z
“Die durchschnittliche Anfallsreduktion war bei Frauen mit insuffizienter Lutealphase größer (59%) als bei Frauen mit perimenstruellen Anfällen (49%) [14, 15] (Tab.”
BackgroundChapter 4.8 – Neuroactive steroids
Rupprecht, R. (2005) · Techniques in the behavioral and neural sciences · doi:10.1016/s0921-0709(05)80030-6
Role of Neurosteroids in Epilepsy
Mtchedlishvili, Z., & Kapur, J. (2003) · Frontiers in neuroscience · doi:10.1201/9780203508169.ch14
Epilepsy and the menstrual cycle
Shafer, P. O., Herzog, A., Morrell, M., & Flynn, K. L. (2003) · doi:10.1017/cbo9780511545030.012
Self-citationHormone replacement therapy and epilepsy
Duncan, S. (2000) · doi:10.1258/136218000100320986
Einfluss von Östrogenen und Gestagenen auf neurologische Erkrankungen
Hufnagel, A., Breckwoldt, M., Hösli, I., Ried, S., Tettenborn, B., & Kuhl, H. (2000) · doi:10.1055/s-2007-1017529
Rolfs, A. (1998) · Der Gynäkologe · doi:10.1007/pl00003093
Epilepsy Case Studies: Pearls for Patient Care
Tatum, W., Sirven, J., & Cascino, G. (2021) · doi:10.1007/978-3-030-59078-9
Progestogens in Non Gynecological Indications
Carp, H., Zolti, M., & Nadjafi-Triebsch, C. (2021) · Progestogens in Obstetrics and Gynecology · doi:10.1007/978-3-030-52508-8_14
Exacerbation of Seizures in a Young Woman
Klein, P. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-374005-2.00042-9
Metadata
- Authors
- Herzog, A. G.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Herzog, Andrew G.
- ORCID
- Herzog, Andrew G.
- Venue
- Neurology
- Published
- 1995-09
- Volume
- 45
- Issue
- 9
- Pages
- 1660-1662
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2011191676
- Cited by
- 218
- References
- 0
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 15 · 2012: 9
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
- Keywords
- progesterone therapy, adjunctive therapy, complex partial seizures, seizure frequency, women, menstrual cycle, adverse drug reactions
- MeSH terms
- Adolescent, Adult, Epilepsy, Generalized, Female, Humans, Progesterone, Epilepsy, Complex Partial
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