By Dr Nicky Keay @nickyKfitness

Menstrual periods are a barometer of healthy hormones. The evolutionary purpose of ovulation is to reproduce. Furthermore the carefully biologically choreographed variation of hormones that occurs during an ovulatory menstrual cycle is crucial to health and athletic performance.

Why? Hormones are chemical messengers that have far reaching effects throughout the body and drive the beneficial adaptations to exercise. In the case of menstrual cycles, the fluctuations of oestrogen and progesterone are key to this process. The effects of these sex steroids go far beyond reproduction. These hormones play important roles in bone strength, cardiovascular health, optimal lipid profile and production of neurotransmitters to regulate mood. The effects of low levels of oestrogen and progesterone are well documented in menopausal women who experience loss in bone mass, risk of osteoporosis and fracture, together with an increase risk of cardiovascular disease.

Some definitions:

• Amenorrhoea=lack of menstrual cycles
• Menarche= start of menstrual cycles
• According to the Royal College of Obstetrics and Gynaecology
• Primary Amenorrhoea: no onset of menstrual cycles by age 16 years.
• Secondary amenorrhoea: cessation of menstrual cycles in a previously regularly menstruating woman for > 6months
• Oligomenorrhoea: < 9 menstrual cycles per calendar year

Any form of amenorrhoea requires medical investigation to exclude an underlying medical condition. The most common medical causes of amenorrhoea are polycystic ovary syndrome (PCOS), prolactinoma, thyroid conditions and other endocrine conditions. Functional hypothalamic amenorrhoea (FHA) is a diagnosis of exclusion. In other words before arriving at a diagnosis of FHA [1], medical conditions that could potentially cause amenorrhoea have to be ruled out.

Relative energy deficiency in sport (RED-S) is a situation of low energy availability (LEA) that can be unintentional or intentional as a result of a mismatch between energy intake and energy requirement. The two sources of energy demand arise from exercise training load and maintenance of fundamental physiological function across multiple body systems [2]. In female athletes/dancers with RED-S the most obvious clinical sign is amenorrhoea as a result of FHA. In all cases of RED-S the management strategy is directed to address the underlying issue of LEA [3].

In female athletes/dancer with FHA due to RED-S, there is the possibility of pharmacological intervention based on the RED-S Clinical Assessment Tool [4]. In other words evidence from DXA of Z-score of lumbar spine < -1 and/or stress fracture. What are the most effect hormonal interventions in such cases?

What’s in a name? 

It’s every woman’s right to choose the form of contraception she wishes to use. Hormonal contraception provides a convenient method. The combined oral contraceptive pill (OCP) contains oestrogen and progesterone to prevent ovulation. The OCP produces regular withdrawal bleeds in response to these external hormones. Progesterone-only contraception can be taken orally, via implant or delivered by an intrauterine coil and typically does not produce withdrawal bleeds. As with any medication there are potential side effects, which have to be weighed up against the benefits. Regarding the effect of hormonal contraception on bone in young menstruating women, there is evidence that such medication can impair bone health [5].

The OCP produces regular withdrawal bleeds. These are NOT menstrual periods; ovulation is prevented. Rather the OCP causes withdrawal bleeds driven by external non-physiological hormones, as opposed to internally physiologically produced hormones. This is a reason why the OCP is not recommended in FHA, as this medication will mask what is happening with internal hormones [6]. In other words the barometer of healthy hormones has been removed when taking the OCP.

Furthermore, studies show that the OCP can impact other hormone systems that play a role in bone health. The OCP is taken orally thereby producing first pass effects in the liver. These effects include induction of liver enzymes and increased production of binding proteins for hormones. Binding proteins reduce the freely available active form of hormones such insulin like growth factor 1 (IGF-1). In the case of RED-S there is already a low level of active IFG-1, due to the general suppression of the hypothalamic-pituitary axis. Therefore, in addition to masking FHA, the OCP can also further decrease IGF-1 and thus compound the negative effect on bone. This has been shown to be the case in the clinical setting where the OCP was found to have no bone protective effect on bone mineral density (BMD) in women with FHA. Rather hormone replacement therapy (HRT) consisting of transdermal physiological oestrogen with cyclic micro-ionised progesterone was found to have a positive effect on BMD [7,8].

If hormonal treatment is to be used in RED-S, HRT (transdermal oestradiol and cyclic micro-ionised progesterone) is best clinical practice. This decision requires careful discussion with the athlete/dancer clarifying that HRT should only be a short-term measure to protect bone health whilst the underlying issue of LEA is being resolved. Behavioural measures relating to training load, nutrition and recovery are essential to restore global hormonal function.

OCP V HRT

• What?Both provide oestrogen and progesterone, but in different forms: non-physiological v physiological
• Why?Purpose of the OCP is to suppress production of endogenous female hormones and prevent ovulation. Purpose of HRT is to replace the physiological amount and form of oestrogen and progesterone
• How?The OCP decreases levels of active, unbound IGF-1. Not bone protective in FHA of RED-S. HRT shown to improve BMD in FHA of RED-S

What to do? 

Hormonal contraception is a choice for women. In some medical conditions where there is adequate/excess oestrogen such as endometriosis or PCOS, hormonal contraception is effective in clinical management. However in the case of FHA, in particular when occurring as a consequence of LEA in RED-S there is evidence that the OCP is not bone protective and masks the clinical sign of menstruation.

The priority in managing RED-S is to address LEA. If bone protection is required, whilst addressing LEA, HRT (transdermal oestradiol and cyclic micro-ionised progesterone) is best clinical practice.

***

Resources

Please refer to BASEM educational website www.health4performance.co.uk

Referrals welcome for NHS RED-S dedicated clinic at Royal National Orthopaedic Hospital, London.

References

[1] Joy, E., De Souza, M. J., Nattiv, A., Misra, M., Williams, N. I., Mallinson, R. J., … Borgen, J. S. (2014). 2014 Female Athlete Triad Coalition Consensus Statement on Treatment and Return to Play of the Female Athlete Triad. Current Sports Medicine Reports, 13(4), 219–232. https://doi.org/10.1249/JSR.0000000000000077

[2] Mountjoy, M., Sundgot-Borgen, J., Burke, L., Carter, S., Constantini, N., Lebrun, C., … Ljungqvist, A. (2014). The IOC consensus statement: Beyond the Female Athlete Triad-Relative Energy Deficiency in Sport (RED-S). British Journal of Sports Medicine, 48(7), 491–497. https://doi.org/10.1136/bjsports-2014-093502

[3] Mountjoy, M., Sundgot-Borgen, J. K., Burke, L. M., Ackerman, K. E., Blauwet, C., Constantini, N., … Budgett, R. (2018). IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update. British Journal of Sports Medicine, 52(11), 687–697. https://doi.org/10.1136/bjsports-2018-099193

[4] Mountjoy, M., Sundgot-Borgen, J., Burke, L., Carter, S., Constantini, N., Lebrun, C., … Ackerman, K. (2015, April 1). Relative energy deficiency in sport (RED-S) clinical assessment tool (CAT). British Journal of Sports Medicine. BMJ Publishing Group. https://doi.org/10.1136/bjsports-2015-094873

[5] Beksinska M, Smit J, Hormonal contraception and bone mineral density. Expert Review of Obstetrics & Gynecology, 2011 vol: 6 (3) pp: 305-319

[6] Gordon, C. M., Ackerman, K. E., Berga, S. L., Kaplan, J. R., Mastorakos, G., Misra, M., … Warren, M. P. (2017). Functional hypothalamic amenorrhea: An endocrine society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism, 102(5), 1413–1439. https://doi.org/10.1210/jc.2017-00131

[7] Ackerman, K. E., Singhal, V., Baskaran, C., Slattery, M., Campoverde Reyes, K. J., Toth, A., … Misra, M. (2018). Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: A randomised clinical trial. British Journal of Sports Medicine. BMJ Publishing Group. https://doi.org/10.1136/bjsports-2018-099723

[8] Singhal,V., Ackerman, K. E., Bose, A., Torre Flores, L. P., Lee, H., & Misra, M. (2018). Impact of Route of Estrogen Administration on Bone Turnover Markers in Oligoamenorrheic Athletes and its Mediators. The Journal of Clinical Endocrinology &Metabolism. https://doi.org/10.1210/jc.2018-02143