Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome
Open accessAbstract
BACKGROUND: The symptoms of women with premenstrual syndrome improve in response to suppression of ovarian function, although these women have no evidence of ovarian dysfunction. We undertook a study to determine the role of estrogen and progesterone in this syndrome. METHODS: We first studied the effect of ovarian suppression with leuprolide, an agonist analogue of gonadotropin-releasing hormone, or placebo on symptoms in 20 women with the premenstrual syndrome. Ten women whose symptoms improved during leuprolide treatment were given estradiol and progesterone in a double-blind, crossover design, each for four weeks, during continued leuprolide administration. Women without premenstrual syndrome (normal women) participated in a similar protocol. Outcomes were assessed on the basis of daily self-reports by the patients and biweekly rater-administered symptom-rating scales. RESULTS: The 10 women with premenstrual syndrome who were given leuprolide had a significant decrease in symptoms as compared with base-line values and with values for the 10 women who were given placebo. The 10 women with premenstrual syndrome who were given leuprolide plus estradiol or progesterone had a significant recurrence of symptoms, but no changes in mood occurred in 15 normal women who received the same regimen or in 5 women with premenstrual syndrome who were given placebo hormone during continued leuprolide administration. CONCLUSIONS: In women with premenstrual syndrome, the occurrence of symptoms represents an abnormal response to normal hormonal changes.
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Prior evidence suggests that individual differences in responsiveness to cycle shifts could be larger in magnitude compared to cycle shifts themselves.
“Prior evidence suggests another possibility, namely that individual differences in responsiveness to cycle shifts could be larger in magnitude compared to cycle shifts themselves [37].”
From Menstrual cycle effects on cognitive performance: A meta-analysis (2025) · cites this paper as [37]
Figure 2 and Table 2 (Discussion; page unavailable) show that women with premenstrual syndrome had increased symptoms after hormone replacement, whereas women without the syndrome did not. That supports differences in responsiveness to hormonal changes, but the paper does not compare the magnitude of those differences with the magnitude of cycle shifts themselves. (LLM, conf=0.84)
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- Authors
- Schmidt, P. J., Nieman, L. K., Danaceau, M. A., Adams, L. F., & Rubinow, D. R.
- Affiliations
- National Institutes of Health (US)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (US)
- National Institute of Mental Health (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1998-01-22
- Volume
- 338
- Issue
- 4
- Pages
- 209-216
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2046110224
- Cited by
- 765
- References
- 28
- Citations by year
- 2026: 30 · 2025: 38 · 2024: 26 · 2023: 27 · 2022: 31 · 2021: 28 · 2020: 21 · 2019: 24 · 2018: 24 · 2017: 26 · 2016: 32 · 2015: 23 · 2014: 24 · 2013: 31 · 2012: 31
- FWCI
- 29.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Upsher-Smith
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Menstrual Health and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- premenstrual syndrome, premenstrual dysphoric disorder, leuprolide, GnRH agonist, ovarian suppression, estradiol, progesterone, estrogen, symptom recurrence
- MeSH terms
- Adult, Double-Blind Method, Emotions, Estradiol, Female, Humans, Gonadotropin-Releasing Hormone, Middle Aged, Premenstrual Syndrome, Progesterone, Leuprolide, Cross-Over Studies, Hot Flashes
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