Clinical and biochemical discriminants between functional hypothalamic amenorrhoea (FHA) and polycystic ovary syndrome (PCOS)

Abstract

Background: Secondary oligo/amenorrhoea occurs in 3%-5% of women of reproductive age. The two most common causes are polycystic ovary syndrome (PCOS) (2%-13%) and functional hypothalamic amenorrhoea (FHA) (1%-2%). Whilst both conditions have distinct pathophysiology and their diagnosis is supported by guidelines, in practice, differentiating these two common causes of menstrual disturbance is challenging. Moreover, both diagnoses are qualified by the need to first exclude other causes of menstrual disturbance.

Aim: To review clinical, biochemical and radiological parameters that could aid the clinician in distinguishing PCOS and FHA as a cause of menstrual disturbance.

Results: FHA is uncommon in women with BMI > 24 kg/m² , whereas both PCOS and FHA can occur in women with lower BMIs. AMH levels are markedly elevated in PCOS; however, milder increases may also be observed in FHA. Likewise, polycystic ovarian morphology (PCOM) is more frequently observed in FHA than in healthy women. Features that are differentially altered between PCOS and FHA include LH, androgen, insulin, AMH and SHBG levels, endometrial thickness and cortisol response to CRH. Other promising diagnostic tests with the potential to distinguish these two conditions pending further study include assessment of 5-alpha-reductase activity, leptin, INSL3, kisspeptin and inhibin B levels.

Conclusion: Further data directly comparing the discriminatory potential of these markers to differentiate PCOS and FHA in women with secondary amenorrhoea would be of value in defining an objective probability for PCOS or FHA diagnosis.

Keywords: functional hypothalamic amenorrhoea; oligo/amenorrhoea; polycystic ovary syndrome (PCOS).

FIGURE 1

(A) The summary statistics of the studies given in Table S1 were used to simulate truncated normal data in the 12–35 kg/m² range for BMI using a Ferguson‐Klass type algorithm for posterior normalized random measures. Instance sizes, histograms and densities of the combined data are shown for controls (left panel), PCOS (centre panel) and FHA (right panel). The y‐axes are density centiles, so 0.15 represents 15% of the total instances. (B) The 481 simulated FHA values are combined with 1000 sampled values from the simulated PCOS data so as to match the proportions expected. For each BMI in the range 16–35 kg/m² the percentage of FHA and PCOS instances are shown. The blue and green percentages sum to 100 for each BMI. The distributions presented are simulations of summative statistics from Table S1 that reflect the same underlying populations but are not exact representations of the distribution of the original data

FIGURE 2

Clinical, biochemical and radiological factors that may aid the clinician in distinguishing functional hypothalamic amenorrhoea (FHA) and polycystic ovarian syndrome (PCOS) in women with secondary oligo/amenorrhoea. OGTT, oral glucose tolerance test; CRH, corticotrophin‐releasing hormone; AMH, anti‐Müllerian Hormone; SHBG, sex hormone binding globulin; LH, luteinising hormone; BMI, body mass index