Hypercortisolism in patients with functional hypothalamic-amenorrhea
Abstract
Hypercortisolism was found in patients with functional hypothalamic amenorrhea (HA) in preliminary short term studies conducted during the morning hours (0800-1100 h). This observation prompted us to characterize the circadian and pulsatile patterns of serum cortisol and LH levels at 15-min intervals for 24 h in 10 women with functional HA and in 7 normal women during the early follicular phase of their cycles. The mean integrated 24-h serum cortisol levels (area under the curve) were significantly (P less than 0.01) higher in the HA patients than in normal women. The mean cortisol levels in the HA patients were elevated (P less than 0.005) compared to those in the normal women during the daytime hours (0800-1600 h), but not during the evening (1600-2400 h) and sleeping hours (2400-0800 h). This selective hypercortisolism during the waking period of the day was almost entirely related to increased duration and amplitude of secretory episodes (peak area) rather than a change in pulse frequency. The serum cortisol increments in response to a noon meal that occurred in normal women were markedly impaired (P less than 0.01) in the HA patients. Compared with that in the normal women, mean LH pulse frequency was reduced by 30% in the HA patients. The 24-h mean LH levels and mean LH pulse amplitude were not significantly different from those in the normal women. However, among the HA patients there were marked individual differences in LH pulse frequency and amplitude, with prolonged interpulse quiescent periods, indicative of dysfunction of the hypothalamic GnRH pulse generator. We conclude that neuroendocrine activation of the ACTH-adrenal axis and inhibition of the GnRH pulse generator in women are associated with HA. Further, spontaneous resumption of normal cyclicity occurred in the majority (8 of 10) of the HA patients with no medical treatment, suggesting that this syndrome is a reversible hypothalamic disorder of a functional nature.
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Human studies have highlighted the profound effect of glucocorticoid excess on the menstrual cycle.
“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 Suh et al., 1988
The model provides insight into how a hyper-sensitized HPG axis may explain amenorrhea secondary to high serum cortisol levels.
“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 Suh et al., 1988
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Loucks, A. B. (2020) · Contemporary Endocrinology · doi:10.1007/978-3-030-33376-8_11 · Cited by 13 · see citing works
Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea
Genazzani, A. D., Bersi, C., Luisi, S., Fruzzetti, F., Malavasi, B., Luisi, M., Petraglia, F., & Genazzani, A. R. (2001) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(01)00094-2 · Cited by 13 · see citing works
Reproductive Function and Low Energy Availability in Exercising Females
Williams, N. I. (1998) · Journal of Dance Medicine & Science · doi:10.1177/1089313x9800200105 · Cited by 13 · see citing works
Kaplan, J. R., Manuck, S. B., Anthony, M. S., et al. (2002) · Obstetrics and Gynecology · doi:10.1097/00006250-200203000-00004 · Cited by 12 · see citing works
- Authors
- SUH, B. Y., LIU, J. H., BERGA, S. L., QUIGLEY, M. E., LAUGHLIN, G. A., & YEN, S. S.
- Affiliations
- University of California San Diego (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1988-04
- Volume
- 66
- Issue
- 4
- Pages
- 733-739
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1987131378
- Cited by
- 146
- References
- 0
- Citations by year
- 2025: 2 · 2023: 1 · 2022: 4 · 2020: 7 · 2018: 2 · 2017: 3 · 2016: 2 · 2014: 5 · 2013: 3
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (RR00827)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-21198, HD-12303-08)
- 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
- functional hypothalamic amenorrhea, hypercortisolism, diurnal cortisol rhythm, luteinizing hormone pulsatility, menstrual cycle resumption, hypothalamic-pituitary-adrenal axis
- MeSH terms
- Adrenocortical Hyperfunction, Adult, Amenorrhea, Circadian Rhythm, Female, Food, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Luteinizing Hormone, Pituitary-Adrenal System, Pulsatile Flow
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