Current understanding of hypothalamic amenorrhoea

Abstract

Hypothalamic amenorrhoea (HA) accounts for approximately 30% of cases of secondary amenorrhoea in women of reproductive age. It is caused by deficient secretion of hypothalamic gonadotrophin-releasing hormone, which in turn leads to failure of pituitary gonadotrophin and gonadal steroid release. Functional HA (FHA) is defined as HA occurring in the absence of a structural lesion and is predominantly caused by significant weight loss, intense exercise or stress. Treatment of FHA is crucial in avoiding the long-term health consequences on fertility and bone health, in addition to reducing psychological morbidity. This article summarises our understanding of the mechanisms underlying FHA, the evidence base for its clinical management and emerging therapies.

Potential Impact of Exercise-Associated Amenorrhea and Subsequent Estrogen Therapy on Cardiovascular Disease Risk Factors in Pre-Menopausal Athletes: A Research Protocol

“…However, hypoestrogenemia can also occur in premenopausal women through disruptions in ovarian function. A major cause of this is reversible, functional hypothalamic amenorrhea (FHA) which is characterized by hypoestrogenemia and secondary amenorrhea [6]. As seen in Figure 1, FHA occurs when the hypothalamic-pituitaryovarian axis is disturbed such that the secretion of GnRH from the hypothalamus is suppressed [6].…”

“…A major cause of this is reversible, functional hypothalamic amenorrhea (FHA) which is characterized by hypoestrogenemia and secondary amenorrhea [6]. As seen in Figure 1, FHA occurs when the hypothalamic-pituitaryovarian axis is disturbed such that the secretion of GnRH from the hypothalamus is suppressed [6]. This decreases the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary [6].…”

“…As seen in Figure 1, FHA occurs when the hypothalamic-pituitaryovarian axis is disturbed such that the secretion of GnRH from the hypothalamus is suppressed [6]. This decreases the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary [6]. In turn, this disrupts ovarian function as the granulosa cells no longer receive a signal to synthesize 17-β estradiol, which leads to hypoestrogenemia (E2 <50 pg/ml) [5,6].…”

“…This decreases the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary [6]. In turn, this disrupts ovarian function as the granulosa cells no longer receive a signal to synthesize 17-β estradiol, which leads to hypoestrogenemia (E2 <50 pg/ml) [5,6]. Moreover, the decreased levels of FSH (<10 mIU/ml) and LH (<10 mIU/ml) during the follicular phase lead to reduced endometrial thickening resulting in amenorrhea [5,6].…”

“…In turn, this disrupts ovarian function as the granulosa cells no longer receive a signal to synthesize 17-β estradiol, which leads to hypoestrogenemia (E2 <50 pg/ml) [5,6]. Moreover, the decreased levels of FSH (<10 mIU/ml) and LH (<10 mIU/ml) during the follicular phase lead to reduced endometrial thickening resulting in amenorrhea [5,6]. Secondary amenorrhea is diagnosed as the lack of menstruation for at least three consecutive months in the absence of other ovarian and anatomic pathologies [5].…”