Introduction
Functional hypothalamic amenorrhoea (FHA) is a common cause of
amenorrhoea and anovulation1,; it is responsible for
up to 3% of primary 2 and 33.5% of secondary
amenorrhoea cases.1 FHA is a form of hypogonadotropic
hypogonadism caused by hypothalamic-pituitary-ovarian (HPO) axis
dysregulation. It is characterised by estradiol deficiency due to
reduced hypothalamic gonadotrophin-releasing hormone (GnRH) secretion.
Common causes include stress, weight loss and excessive
exercise.1
Early FHA diagnosis is crucial to prevent complications such as
osteoporosis and infertility secondary to anovulation. FHA features,
such as low body mass index (BMI) and psychological stress, can cause
complications, if pregnancy does occur; mothers with low BMI are more
likely to have miscarriages 3, give birth prematurely
and have low birth weight babies.4 Furthermore,
prolonged hypoestrogenemia reduces bone mineral density (BMD), causing
osteopenia and osteoporosis and has significant negative impacts on the
cardiovascular system.
5-7
Eighty three percent of FHA cases are reversible, when causative factors
are addressed.
8 The 2017 Endocrine Society Guidelines recommend
first-line treatment of FHA should aim to energy availability by
improving nutrition, supporting weight gain and reducing exercise.
9 However, FHA diagnosis may be complicated by an
indistinct clinical picture and confusion with another common cause of
menstrual disturbance: polycystic ovary syndrome (PCOS). The typical
hormone profile in PCOS has some reported distinctions from FHA, namely:
elevated LH: follicle-stimulating hormone (FSH) ratio and free
testosterone; reduced sex hormone binding globulin; and normal
estradiol, prolactin, cortisol and thyroid hormones.10 However, many women with FHA or PCOS display
non-typical hormone profiles. Furthermore, up to 40% of women with FHA
have features of polycystic ovarian morphology (PCOM) on ultrasound.
11,12 PCOS usually presents with oligomenorrhea or
eumenorrhea but can also present with amenorrhoea. In contrast to FHA,
PCOS treatment involves controlling hyperandrogenism symptoms and
reducing metabolic risk. The Endocrine Society recommends hormonal
contraceptives in PCOS to regulate periods13, however
the oral contraceptive pill is not recommended for FHA since they
provide inferior bone mineralisation, when compared with hormone
replacement therapy.
9 Failure to detect FHA can also result in failure to
address underlying psychological comorbidities. Few studies have
compared the clinical and biochemical features of FHA with other causes
of amenorrhoea and there remains limited data on the diagnostic
performance of parameters such as estradiol, LH and BMI, in
distinguishing between FHA and PCOS.
Our study aimed to investigate the clinical and biochemical features of
FHA and comparing it to that of women with PCOS. Additionally, we
explored the diagnostic performance of these parameters in
distinguishing between FHA and PCOS.