The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index; none of the 31 sources its claims cite is checked for support yet.
Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids1
Abstract
To determine whether cortisol has an effect on hypothalamic-pituitary-gonadal function, we studied 11 eumenorrheic women in the early follicular phase of consecutive menstrual cycles by performing daytime 10-min blood sampling, one before and one during hydrocortisone administration. Daily blood sampling for gonadotropins and sex steroids was also performed. LH pulsations were determined by modification of a widely used threshold method and compared by paired t-testing. The LH interpulse interval was significantly prolonged (95 +/- 5 to 119 +/- 14 min; p = 0.001), and the mean LH pulse amplitude remained unchanged (1.3 +/- 0.1 and 1.5 +/- 0.2 mIU/ml) with glucocorticoid exposure. Mean estradiol was not altered (46 +/- 5 and 43 +/- 3 pg/ml), but mean LH and FSH from pooled serum aliquots were slightly but significantly reduced (2.6 +/- 0.2 to 2.2 +/- 0.2, 5.5 +/- 0.4 to 4.5 +/- 0.3 mIU/ml; p = 0.004, 0.012, respectively). Mean progesterone levels were also decreased (0.8 +/- 0.3 to 0.5 +/- 0.2 ng/ml; p = 0.011) in the presence of exogenous glucocorticoid. Twenty-four-hour urinary free cortisol levels confirmed a substantial increase in free cortisol excretion (74 +/- 10 to 305 +/- 50 micrograms/day; p = 0.001). These results demonstrate that cortisol can slow LH pulse frequency and, by inference, hypothalamic GnRH secretion, in a manner that appears independent of corticotropin releasing factor. Excess cortisol alone may therefore play a role in the development of stress-assoc…
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10 Own interpretation · 9 Sources not found · 9 Own result · 7 No full text of the sources · 5 Own method · 4 Not checked yet · 3 No basis given
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the mean LH pulse amplitude remained unchanged (1.3 + 0.1 and 1.5 ± 0.2 mlU/ml) with glucocorticoid exposure.”
- Also stated in: § 119 · plain
“Mean LH pulse amplitude remained unchanged (1.3 + 0.1 mIU/ml vs. 1.5 + 0.2 mIU/ml,p = 0.231).”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > Abstract
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“Mean serum LH decreased from 2.6 + 0.2 to 2.2 ± 0.2 mIU/ml (p = 0.004) before and during glucocorticoid administration.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > Pooled sera.
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“Mean serum FSH concentrations were also significantly lower: 5.5 ± 0.4 to 4.5 + 0.3 mIU/ml (p = 0.012).”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > Pooled sera.
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“Mean serum E concentrations were unchanged (46 + 5 vs. 43 3 pg/ml, p = 0.257)”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > Pooled sera.
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“All patients experienced subsequent menses at the time expected according to prior cycle length.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > General Characteristics of the Study Cycles 1B
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“The modest degree of slowing observed did not result in any disturbance in the onset of the menstrual cycle during which the volunteers were exposed to cortisol or the subsequent menstrual cycle off medication.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > 700-
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“No correlation was noted between the free cortisol increment and the degree of slowing of LH pulsations.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > Pooled sera.
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“24-h urinary free cortisol levels confirmed a substantial increase in free cortisol (74 ± 10 vs. 305 ± 50 ,ag/d, p = 0.001, Fig. 3).”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > Pooled sera.
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“Total serum cortisol did not vary with exogenous glucocorticoid exposure (9.5 ± 0.5 vs. 8.6 + 0.7 [tg/dl,p = 0.254)”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > Pooled sera.
plain- Asserted: passes — The authors put it forward as true.
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“There was no acute effect of cortisol on serum sex steroids and gonadotropins during the luteal phase.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > General Characteristics of the Study Cycles 1B
plain- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 12
- Probably not a substantial claim. 9
- The quote only partly states this claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The LH interpulse interval was significantly prolonged (95 ± 5 to 119 + 14 min;p = 0.001)”
- Also stated in: § 119 · plain
“Similarly, LH pulse frequency was significantly slowed (7.7 + 0.4 pulses/12 h vs. 6.6 + 0.5 pulses/12 h,p = 0.007).”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > Abstract
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- Also stated in: § 119 · plain
In the paper
“Therefore, using each woman as her own control in successive early follicular phases is useful for demonstrating differences in LH pulse frequency when interventions are employed, although serial cycle sampling may be relatively insensitive [35].”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > DISCUSSION
What the sources say
- Not matchedcites [35] 35. Weltman JY, Seip RL, Weltman A, Snead D, Evans WS, Veldhuis JD, Rogol AD. Release of luteinizing hormone and growth hormone after recovery from max- imal exercise. J Appl Physiol 1990; 69:196-200.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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In the paper
“Cortisol has been shown to inhibit gonadotropin secretion directly in vitro [20] and indirectly in vivo, as determined by the ability of i.v.GnRH to restore normal gonadotropin secretion in hypogonadotropic, hydrocortisone-treated animals [21].”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [20] 20. Padmanabhan V, Keech C, Convey EM. Cortisol inhibits and adrenocorticotropin has no effect on luteinizing hormone-releasing hormone-induced release of lu- teinizing hormone from bovine pituitary cells in vitro. Endocrinology 1983; 112:1782-1787. source
- Not checked — no full text of the sourcecites [21] 21. Dubey AK, Plant TM. A suppression of gonadotropin secretion by cortisol in cas- trated male rhesus monkeys (Macaca mulatta) mediated by the interruption of hypothalamic gonadotropin-releasing hormone release. Biol Reprod 1985; 33:423- 431. source
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In the paper
“Hypercortisolemia has also been reported in women with menstrual disorders [2,[5][6][7][8][9][10][11].”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > INTRODUCTION
What the sources say
- Not matchedcites [2,[5][6][7][8][9][10][11]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Animal studies have linked increased corticotropin releasing factor (CRF) to decreased LH [12,13] and FSH [12] secretion and hypercortisolemia.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > INTRODUCTION
What the sources say
- Not matchedcites [12] 12. Olster DH, Ferin M. Corticotropin-releasing hormone inhibits gonadotropin se- cretion in the ovariectomized rhesus monkey. J Clin Endocrinol & Metab 1987; 65:262-267.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [13] 13. Rivier C, Vale W. Influence of corticotropin-releasing factor on reproductive func- tions in the rat. Endocrinology 1984; 114:914-921. source
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In the paper
“Intraassay coefficients of variation (CVs) for LH were 3% at 1 mIU/ml, 2.5% at 5 mIU/ ml, and 2% at 50 mIU/ml; interplate interassay CVs were 6%, 6%, and 4.5%, respectively.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > Assays
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“As it has recently been suggested that circulating P in the early follicular phase of the menstrual cycle originates from the adrenal gland [51]”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > 700-
What the sources say
- Not checked — no full text of the sourcecites [51] 51. Judd S, Terry A, Petrucco M, White G. The source of pulsatile secretion of pro- gesterone during the human follicular phase. J Clin Endocrinol & Metab 1992; 74:299-305. source
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In the paper
“The experimental paradigm used created a steroid environment that was temporary but similar to that of women with hypothalamic amenorrhea and may serve as a model with which to study the pathophysiology of such a glucocorticoid-mediated effect.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > 700-
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“This assay is sensitive [24] and specific, and measures activity against the WHO Second IRP-LH/FSH standard.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > Assays
What the sources say
- Not checked — no full text of the sourcecites [24] 24. Santoro N, Schneyer AL, Ibrahim J, Schmidt CL. Gonadotropin and inhibin con- centrations in early pregnancy in women with and without corpora lutea. Obstet Gynecol 1992; 79:579-585.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“the effect of hydrocortisone on ambient P can plausibly be explained if the cortisol excess resulted in negative feedback on adrenal P production.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > 700-
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“However, it is also possible that nonrandomization of our patients allowed a consistent bias to be introduced into the study.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Although the protocol used here relied solely on menstrual dating of the cycles for planning blood-sampling sessions, the low E and P values observed and the agreement with previous investigators confirm that subjects were sampled in the early follicular phase in both study cycles.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [27] 27. Filicori M, Santoro N, Merriam GR, Crowley WF. Characterization of the physi- ological pattern of episodic gonadotropin secretion throughout the human men- strual cycle. J Clin & Endocrinol Metab 1986; 62:1136-1144. source
- Not matchedcites [38] 38. Reame N, Sauder SE, Kelch RP, Marshall JC. Pulsatile gonadotropin secretion dur- ing the human menstrual cycle: evidence for altered frequency of gonadotropin- releasing hormone secretion. J Clin Endocrinol & Metab 1984; 59:328-337.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Direct implantation of CRF into the brain of rodents was observed to inhibit LH secretion [13], and peripheral infusion of CRF decreased LH and FSH secretion in the monkey [12].”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [13] 13. Rivier C, Vale W. Influence of corticotropin-releasing factor on reproductive func- tions in the rat. Endocrinology 1984; 114:914-921. source
- Not matchedcites [12] 12. Olster DH, Ferin M. Corticotropin-releasing hormone inhibits gonadotropin se- cretion in the ovariectomized rhesus monkey. J Clin Endocrinol & Metab 1987; 65:262-267.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In one patient the first 12-h sampling session was stopped after 510 min (8.5 h) because of a hemoglobin level less than 10 g/dl.The LH pulse frequency was adjusted for 720 min and reported as 5.6 pulses.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > 119
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In the paper
“The intensive phlebotomy regimen required by this protocol did not allow for daily sampling through a second cycle; therefore subtle changes could not be evaluated.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > 700-
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“Use of this compound, which binds to corticotropin binding globulin rather than synthetic analogues, may be one reason why supraphysiologic exposure yielded differences in GnRH secretion.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > 700-
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“These data suggest that cortisol may act at both the hypothalamic and pituitary levels to reduce GnRH pulse frequency and pituitary LH and FSH secretion.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Alternatively, metabolic clearance differences induced by the hypercortisolemia may have accounted for the slight but significant decrements in mean LH, FSH, and P that were observed.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > 700-
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
The authors state this as an assumption.
Hydrocortisone administration suppressed endogenous CRF sufficiently that the observed slowing of LH pulse frequency cannot be attributed to CRF.
“in a manner that appears independent of corticotropin releasing factor.”
“The experiment described in this report suggests that cortisol can influence LH (and inferentially GnRH) pulse frequency presumably in the face of suppressed CRF.”
Claims other papers make about this one
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In the citing paper
“In multiple species, psychosocial stress exposure or treatment with exogenous CORT inhibited the pulsatile release of LH79–81”
From Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling (2018) · cites this paper as [79]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Human studies have also highlighted the profound effect of glucocorticoid excess on the menstrual cycle (Ding et al., 1988; Suh et al., 1988; Saketos et al., 1993; Crofford et al., 1999).”
From Dynamic Hormone Control of Stress and Fertility (2020) · cites this paper as Saketos et al., 1993
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Thus, our model provides insight into how for example a hyper-sensitized HPG axis may explain amenorrhea secondary to high serum cortisol levels (Ding et al., 1988; Suh et al., 1988; Saketos et al., 1993).”
From Dynamic Hormone Control of Stress and Fertility (2020) · cites this paper as Saketos et al., 1993
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In the paper
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > INTRODUCTION
“We studied consecutive menstrual cycles in amenorrheic women before and during exposure to hydrocortisone.”
§ Suppression of the Hypothalamic-Pituitary-Ovarian Axis in Normal Women by Glucocorticoids' > Patient Selection
“The study population was composed of 11 eumenorrheic women 19-38 yr of age.All 1) reported regular menstrual cycles between 25 and 35 days duration;”
Citations
Cites
Santen, R. J., & Bardin, C. W. (1973) · Journal of Clinical Investigation · doi:10.1172/jci107454 · Cited by 706
Filicori, M., Butler, J. P., & Crowley, W. F. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111370 · Cited by 547
FILICORI, M., SANTORO, N., MERRIAM, G. R., & CROWLEY, W. F. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-62-6-1136 · Cited by 489
Self-citationThe Physiology of Gonadotropin-Releasing Hormone (GnRH) Secretion in Men and Women
Crowley, W. F., Filicori, M., Spratt, D. I., & Santoro, N. F. (1985) · Elsevier eBooks · doi:10.1016/b978-0-12-571141-8.50015-9 · Cited by 485
Self-citationLoucks, A. B., Mortola, J. F., GIRTON, L., & Yen, S. S. C. (1989) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-68-2-402 · Cited by 478
Abnormal Hypothalamic–Pituitary–Adrenal Function in Anorexia Nervosa
Gold, P. W., Gwirtsman, H. E., Avgerinos, P. C., Nieman, L. K., Gallucci, W. T., Kaye, W. H., Jimerson, D. C., Ebert, M. H., Rittmaster, R. S., Loriaux, D. L., et al. (1986) · New England Journal of Medicine · doi:10.1056/nejm198605223142102 · Cited by 457
Ovarian and adrenal contribution to peripheral androgens during the menstrual cycle
ABRAHAM, G. E. (1974) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-39-2-340 · Cited by 436
LEVINE, J. E., PAU, K.-Y. F., RAMIREZ, V. D., & JACKSON, G. L. (1982) · Endocrinology · doi:10.1210/endo-111-5-1449 · Cited by 384
Influence of Corticotropin-Releasing Factor on Reproductive Functions in the Rat*
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Metadata
- Authors
- Saketos, M., Sharma, N., & Santoro, N. F.
- Affiliations
- Rutgers New Jersey Medical School (US)
- Corresponding author
- Santoro, Nanette F.
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 1993-12-01
- Volume
- 49
- Issue
- 6
- Pages
- 1270-1276
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- OpenAlex
- W2096686035
- Cited by
- 144
- References
- 54
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 7 · 2023: 6 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 2 · 2018: 5 · 2017: 8 · 2016: 4 · 2015: 7 · 2014: 4 · 2013: 6 · 2012: 5
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biology of Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- glucocorticoids, cortisol, hypothalamic-pituitary-ovarian axis, luteinizing hormone pulsatility, LH pulse frequency, GnRH secretion, gonadotropins, estradiol, progesterone, eumenorrheic women, follicular phase
- MeSH terms
- Adult, Estradiol, Female, Follicular Phase, Follicle Stimulating Hormone, Glucocorticoids, Humans, Hydrocortisone, Hypothalamus, Luteinizing Hormone, Menstruation, Ovary, Periodicity, Pituitary Gland, Progesterone
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