Effects of low energy availability on female reproductive function

Takeshi Iwasa; Saki Minato; Junki Imaizumi; Atsuko Yoshida; Takako Kawakita; Kanako Yoshida; Yuri Yamamoto

doi:10.1002/rmb2.12414

Reproductive Endocrinology · Neuroendocrinology

Effects of low energy availability on female reproductive function

Iwasa T, Minato S, Imaizumi J, Yoshida A, Kawakita T, Yoshida K, Yamamoto Y

Reproductive medicine and biology, 21(1), e12414, 2022

DOI 10.1002/rmb2.12414 PMID 34934398 PMC PMC8656184

RRM Academy Synopsis

Low energy availability suppresses GnRH and female reproduction

Low energy availability suppresses GnRH, the brain hormone that drives ovulation and periods. The 2022 review covers human and animal studies. Leptin, insulin, kisspeptin and hunger hormones shape GnRH release as energy status changes. The authors suggest the response may protect survival by pausing reproduction for a time.

Key Findings

The authors' own study of hypothalamic-pituitary causes of irregular menses or secondary amenorrhea attributed 38% of cases to body weight loss and 3% to psychological stress or exercise.
Females with hypothalamic amenorrhea, mainly caused by weight loss, had lower mean LH levels and lower LH pulse frequency in the early follicular phase than normal females.
LH pulse frequency did not decrease linearly with energy status. It was disrupted when energy availability fell below a threshold level.
Satiety-related factors (leptin, insulin, alpha-melanocyte-stimulating hormone) facilitate GnRH. Orexigenic factors (NPY, AgRP, orexin, ghrelin) suppress GnRH. Low energy availability lowers the first group and raises the second.
In prepubertal female rats, undernutrition reduced hypothalamic Kiss1 expression and disturbed puberty. In these rats, giving kisspeptin from outside restored normal gonadotrophin secretion and pubertal timing.

Interpretation

The paper is a narrative review with no stated search method. Much of the mechanism data come from mice, rats, sheep and monkeys, so the exact mechanisms in women remain unclear. Human evidence includes hormone levels in women with hypothalamic amenorrhea. It also includes delayed puberty in dancers in heavy training and the authors' own case analysis. The link between leptin and kisspeptin is unresolved: mice lacking the leptin receptor in kisspeptin neurons kept normal sexual maturity and fertility. In animal models, diet-induced obesity and diabetes also lowered hypothalamic Kiss1 expression.

RRM Context

Restorative reproductive medicine asks why ovulation stopped. Brain signals of energy status offer one answer, and cycle charting shows the pattern as it unfolds. The authors conclude that metabolic and nutritional health matters in preconception care.

Our editorial summary of this paper, not the article's abstract.

Abstract

Background

It is known that metabolic and nutritional disturbances induce reproductive dysfunction in females. The main cause of these alterations is reduced gonadotrophin-releasing hormone (GnRH) secretion from the hypothalamus, and the underlying mechanisms have gradually been elucidated.

Methods

The present review summarizes current knowledge about the effects of nutrition/metabolism on reproductive functions, especially focusing on the GnRH regulation system.

Main Findings

Various central and peripheral factors are involved in the regulation of GnRH secretion, and alterations in their activity combine to affect GnRH neurons. Satiety-related factors, i.e., leptin, insulin, and alpha-melanocyte-stimulating hormone, directly and indirectly stimulate GnRH secretion, whereas orexigenic factors, i.e., neuropeptide Y, Agouti-related protein, orexin, and ghrelin, attenuate GnRH secretion. In addition, kisspeptin, which is a potent positive regulator of GnRH, expression is reduced by metabolic and nutritional disturbances.

Conclusion

These neuroendocrine systems may be defensive mechanisms, which help organisms to survive adverse conditions by temporarily suppressing reproduction.

Topics

Reproductive Endocrinology › Neuroendocrinology › Hypothalamic Amenorrhea · Lifestyle and Environment › Nutrition and Metabolic Health › Eating Disorders and Underfueling

Takeshi Iwasa, Saki Minato, Junki Imaizumi, Atsuko Yoshida, Takako Kawakita, Kanako Yoshida, Yuri Yamamoto

T Iwasa, S Minato, J Imaizumi, A Yoshida, T Kawakita, K Yoshida, Y Yamamoto

PMID 34934398 34934398 DOI 10.1002/rmb2.12414 10.1002/rmb2.12414 Iwasa et al. 2022, Iwasa 2022

Keywords

GnRH, hypothalamus, kisspeptin, metabolism, nutrition

Effects of low energy availability on female reproductive function

Low energy availability suppresses GnRH and female reproduction

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

Related research

Keywords