The functional integrity of the hypothalamic-pituitary-ovarian and hypothalamic-pituitary-adrenal axes was assessed by determining pulsatile LH, ACTH, and cortisol secretion during the early follicular phase in athletic women with regular menstrual cycles (CA; n = 9), athletic women with amenorrhea (AA; n = 9), and regularly cyclic sedentary women (CS; n = 8). The CA and AA women were not significantly different in body composition, exercise training, psychometric tests, or dietary consumption. The CA women had shorter luteal phases (P less than 0.05) and lower urinary excretion of pregnanediol glucuronide than the CS women. In the AA women, urinary estrone glucuronide, pregnanediol glucuronide, and LH excretion were low throughout a 30-day period. The CA women had a 24-h pattern of pulsatile LH secretion characterized by reduced frequency (P less than 0.05) and increased amplitude (P less than 0.05), yielding an overall increased 24-h mean level (P less than 0.05), but interpulse intervals similar to those in the CS women. During sleep, LH pulse frequency slowed in the CS and CA women, while pulse amplitude increased and the mean serum LH level decreased in both groups. The AA women had even fewer pulses (P less than 0.05) of normal amplitude occurring at much more variable (P less than 0.01) interpulse intervals. Sleep-associated changes in LH pulsatility were absent. Responses to a 10-microgram bolus GnRH dose revealed blunted (P less than 0.05) FSH release in CA and augmented (P less than 0.05) LH release in AA women. The groups did not differ in any 24-h ACTH pulse pattern parameter or in cortisol pulse frequencies. Yet, early morning (0200-0800 h) serum cortisol levels were higher (P less than 0.05) in both groups of athletes, and this elevation was extended through the day (0800-2000 h; P less than 0.001) and evening (2000-0200 h; P less than 0.05) in the AA women. The plasma ACTH and serum cortisol responses to bolus human CRH administration were blunted in the CA and AA women [change from baseline (delta) in ACTH, P less than 0.05 and P less than 0.01; delta cortisol, P less than 0.01 and P less than 0.01, respectively], but adrenal sensitivity (delta cortisol/delta ACTH ratio) was increased (P less than 0.05). The plasma ACTH and serum cortisol responses to meals also were blunted in the athletic groups (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
hypothalamic pituitary ovarian axis athletic women amenorrhea, exercise-associated amenorrhea LH pulsatility cortisol elevation, Loucks Yen athletic women menstrual dysfunction HPA axis, luteal phase deficiency athletic women regular menstrual cycles, pulsatile LH secretion frequency amplitude athletic amenorrhea, hypothalamic pituitary adrenal axis cortisol exercise female athletes, functional hypothalamic amenorrhea exercise training body composition, CRH stimulation test ACTH cortisol response athletic women, GnRH bolus FSH LH response athletic amenorrhea, sleep-associated LH pulsatility changes exercise amenorrhea, adrenal sensitivity cortisol ACTH ratio female athletes
PMID 2537332 2537332 DOI 10.1210/jcem-68-2-402 10.1210/jcem-68-2-402 Loucks et al. 1989, Loucks 1989
Cite this article
Loucks, A. B., Mortola, J. F., Girton, L., & Yen, S. S. (1989). Alterations in the hypothalamic-pituitary-ovarian and the hypothalamic-pituitary-adrenal axes in athletic women. The Journal of clinical endocrinology and metabolism, 68(2), 402-411. https://doi.org/10.1210/jcem-68-2-402
Loucks AB, Mortola JF, Girton L, Yen SS. Alterations in the hypothalamic-pituitary-ovarian and the hypothalamic-pituitary-adrenal axes in athletic women. J Clin Endocrinol Metab. 1989;68(2):402-411. doi:10.1210/jcem-68-2-402
Loucks, A. B., et al. "Alterations in the hypothalamic-pituitary-ovarian and the hypothalamic-pituitary-adrenal axes in athletic women." The Journal of clinical endocrinology and metabolism, vol. 68, no. 2, 1989, pp. 402-411.
The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society.
To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA). The participants include an Endocrine Society-appointed task force of eight experts, a methodologist, and a medical writer. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline. FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation.
Leyendecker G et al., 1980·J Clin Endocrinol Metab·
In previous studies it could be demonstrated that in severe hypothalamic amenorrhea, which is associated with absent or deficient hypothalamic secretion of Gn-RH, ovarian function could be restored by chronic intermittent (pulsatile) administration of Gn-RH. In order to apply chronic intermittent administration of Gn-RH as a new mode of treatment of infertility in hypothalamic amenorrhea on an outpatient basis a portable device ("Zyklomat") was constructed consisting of a peristaltic pump, a computerized timing device and a Gn-RH containing bag, which delivers 50 microliters of a Gn-RH containing solution once every 90 minutes via an i.v. catheter into the circulation. It is the purpose of this communication to present this new method of treatment and the successful induction of the first two pregnancies with this method in two patients with severe hypothalamic amenorrhea.
Functional hypothalamic amenorrhoea (FHA) is a common cause of amenorrhoea, but diagnosis can be challenging. The aim of this study was to investigate the clinical and biochemical features of FHA, compared to that of polycystic ovarian syndrome (PCOS) and assess the diagnostic performance of the different parameters for differentiating the two conditions. This was a retrospective observational study. We analysed clinical and biochemical parameters of women diagnosed with FHA and PCOS following specialist assessment at the reproductive endocrine gynaecology clinic, St Mary's Hospital. Compared with PCOS, women with FHA had significantly lower body mass index (BMI; 20.1 ± 2.9 vs. 31.1 ± 7.8 kg/m2 ; p< .0001) and a thinner endometrium (3.75 ± 2.23 vs. 6.82 ± 3.32 mm; p< .0001). Women with FHA had significantly lower luteinising hormone (LH; 3.46 ± 7.31 vs. 8.79 ± 4.98 IU/L; p< .0001), and lower LH to follicle-stimulating hormone (FSH) ratio, estradiol, thyroid-stimulating hormone, free thyroxine and prolactin levels; there was no significant difference in FSH levels. BMI had the greatest predictive performance for FHA (area under the curve [AUC]: 0.93; p< .001), followed by estradiol (AUC: 0.89; p< .001), LH (AUC: 0.88; p< .001) and LH:FSH ratio (AUC: 0.86; p< .001). Our data provides quantification for diagnostic accuracy of clinical parameters to differentiate FHA from PCOS, namely low BMI, estradiol, LH and LH:FSH ratio. These data could help clinicians more reliably diagnose FHA in women with secondary amenorrhoea.
Golden NH et al., 2008·Annals of the New York Academy of Sciences
Menstrual irregularity is a common occurrence during adolescence, especially within the first 2-3 years after menarche. Prolonged amenorrhea, however, is not normal and can be associated with significant medical morbidity, which differs depending on whether the adolescent is estrogen-deficient or estrogen-replete. Estrogen-deficient amenorrhea is associated with reduced bone mineral density and increased fracture risk, while estrogen-replete amenorrhea can lead to dysfunctional uterine bleeding in the short term and predispose to endometrial carcinoma in the long term. In both situations, appropriate intervention can reduce morbidity. Old paradigms of whom to evaluate for amenorrhea have been challenged by recent research that provides a better understanding of the normal menstrual cycle and its variability. Hypothalamic amenorrhea is the most prevalent cause of amenorrhea in the adolescent age group, followed by polycystic ovary syndrome. In anorexia nervosa, exercise-induced amenorrhea, and amenorrhea associated with chronic illness, an energy deficit results in suppression of hypothalamic secretion of GnRH, mediated in part by leptin. Administration of recombinant leptin to women with hypothalamic amenorrhea has been shown to restore LH pulsatility and ovulatory menstrual cycles. The use of recombinant leptin may improve our understanding of the pathophysiology of hypothalamic amenorrhea in adolescents and may also have therapeutic possibilities.