Under the Radar: Relative Energy Deficiency in Sport

Continuing our series on diagnoses that might have been missed, Dr Nicolas Alexander describes a case of Relative Energy Deficiency in Sport (RED-S) that had initially been labelled as PCOS

A 30-year-old female patient presented to our practice with 6 months of amenorrhoea since stopping the combined oral contraceptive pill (COCP). She had a prior history of inconsistent periods, and had been on the COCP for a number of years to help regulate them. She was now keen to become pregnant and presented with concerns around her fertility.

Blood tests showed she had normal LH, FSH, oestrogen, progesterone, testosterone, Sex Hormone Binding Globulin, thyroid function and Free Androgen Index. Prolactin was also checked and found to be normal.

An USS of the pelvis showed multiple peripheral follicles (>12 in each ovary).

The patient had been given an initial label of PCOS, but missed a telephone consultation with her original GP and was booked in with me for review of the above. 

Looking at her history, I noted that while this picture might seem to fit with PCOS, she had no other key features – no acne or hirsutism, and her bloods were completely normal, with no raised testosterone.

From her self-reported weight her BMI was over 20, but when weighed in the surgery it was 19.23. Though not considered underweight according to guidelines this is at the lower end of normal.

All this made me sceptical of the initial PCOS diagnosis and so I explored her weight and her exercise levels, given their potential link with amenorrhoea.

On further questioning, she reported taking vigorous exercise at least five times a week – high intensity interval training, spin classes, running and cycling to work every day. She also had an active job working in the sports department at a university. 

I considered a more likely diagnosis could be hypothalamo-pituitary dysfunction related to her excessive exercise and low weight – consistent with RED-S (Relative Energy Deficiency in Sport). This seemed to chime with the patient based on reading she had done. I offered a further blood test to check 9am cortisol, as elevation supports the diagnosis. But as this would not change the plan, we agreed to hold off this.

I advised measures to increase her weight and reduce the amount of high intensity physical exercise she was engaging in, and that her periods should then return, though this may not be immediate.

The patient returned several months later as her periods had still not returned. Despite reporting she had tried to eat more and exercise less, she had gained no weight. After further discussion around the importance of adequate food intake, including carbohydrate, and reducing activity, she agreed to continuing with the approach for a further trial period.

At review six months later her weight had increased by 1.5 kg, she had improved her diet, was doing less strenuous exercise less often, and her periods had returned to normal.

Learning points

It can be challenging to differentiate PCOS and RED-S where menstrual dysfunction and other clinical features overlap, and as a result it’s possible to fall into the diagnostic trap of assuming the more common disorder.

A diagnosis of PCOS requires two of the three following features are present:

• Ovulatory dysfunction (infrequent or no periods)
• Clinical and/or biochemical signs of hyperandrogenism (acne, hirsutism, or elevated levels of total or free testosterone)
• Polycystic ovarian morphology on ultrasound scan (now defined as 20 or more follicles per ovary in the latest 2023 guidelines; previously this was 12 or more follicles per ovary).

In this case, the patient had an insufficient number of cysts to meet the third (new) diagnostic criterion, and an absence of any clinical or biological signs of hyperandrogenism. She also had a relatively low BMI which in my experience is unusual in PCOS.

RED-S is a recently recognised condition and still poorly understood. Its description sought to dispel the myth that menstrual irregularities are a normal part of sport in females (‘the female athlete triad’), when these are actually a symptom of the underlying hypothalamo-pituitary dysfunction that occurs in both males and females and has wider multisystem consequences.

There are no specific diagnostic criteria for RED-S but it should be suspected in men and women who are very active in sports, both amateur and professional, particularly those who are underweight or at the lower end of normal weight and who present with features of its multisystem effects such as:

• Metabolic – menstrual disturbance; lack of morning erections.
• Psychological – low mood, poor concentration, fatigue, irritability, sleep disturbance.
• Immune function – frequent minor illness.
• Musculoskeletal – frequent injuries; falling strength; reduced endurance.

Investigations should focus on excluding other endocrine disturbance and identifying the impaired hormone axis.  In women, these include the usual investigations for amenorrhoea such as pregnancy test, LH, FSH, oestradiol, testosterone, TFTs, prolactin, and also notably 9am cortisol, elevation of which can be a key factor in distinguishing RED-S from other potential underlying conditions, including PCOS.

Treatment is with education, adequate nutritional intake/fuelling (particularly adequate carbohydrate intake), reducing the intensity and frequency of exercise and increasing weight.

Medicating the symptoms (eg, with antidepressants, or OCP) won’t fix the issue as this will fail to correct the underlying drivers of hormone dysfunction – namely the energy deficit and associated over-exertion. Input from other specialties may be necessary such as dietetics, endocrine, sports medicine and psychiatry (if an eating disorder suspected).

Dr Nicolas Alexander is a GP and GP trainer in North East London

Further reading  

British Association of Sport and Exercise Medicine. Health for Performance – Relative Energy Deficiency in Sport (RED-S)  

Project RED-S: Nothing beats sustainable performance

BMJ Blogs – 2018 Update: Relative Energy Deficiency in Sport (RED-S)  Br J Sports Med; Published 30 May 2018