What’s so good about menstrual cycles?

BY DR NICKY KEAY

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 occur during an ovulatory menstrual cycle are 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 fluctuation of oestrogen and progesterone are key to this process.

The effects of these sex steroids go far beyond bone health. These hormones play an important role in 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 per se.

Functional hypothalamic amenorrhoea (FHA) is a diagnosis of exclusion. In other words before arriving at a diagnosis of FHA[i], 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 mismatch between energy intake and energy requirement.

The two sources of energy demand are:

  1. To cover exercise training load

  2. To maintain fundamental physiological function across multiple body systems[ii].

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 direct to address the underlying issue of LEA[iii].

In female athletes/dancer with FHA due to RED-S, there is the possibility of pharmacological intervention based on RED-S Clinical Assessment Tool[iv]. 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 is every woman’s right to chose the form of contraception she wishes to use. Hormonal contraception provides a convenient method. Combined oral contraceptive pill (OCP) contains oestrogen and progesterone to prevent ovulation. OCP produces regular withdrawal bleeds in response to these external hormones.

Progesterone only contraception, which can be taken orally, via implant or delivered intrauterine coil and typically do 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[v]

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

Furthermore, studies show that OCP can impact other hormone systems that play a role in bone health. OCP is taken orally therefore subject to first pass effect via liver, which induces liver enzymes and increase production of binding proteins for hormones. This includes increased binding of insulin like growth factor 1 (IGF-1). In the case of RED-S there is a general suppression of the hypothalamic axis, which results in FHA and low levels of active IFG-1.

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 clinical setting where 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[vii], [viii]  

Therefore, 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 athlete/dancer so that it is appreciated that this short term measure and concurrent with behavioural measures relating to training load, nutrition and recovery to address LEA. 

OCP V HRT

  • What? Both provide oestrogen and progesterone, but in different forms: non-physiological v physiological

  • Why? Purpose of OCP is to supress production of endogenous female hormones and prevent ovulation. Purpose of HRT is to replace physiological amount and form of oestrogen and progesterone

  • How? 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 OCP is not bone protective, increases binding proteins and hence lowers IFG-1 further 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 oestrogen and cyclic progesterone) is best clinical practice.

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 Reports13(4), 219–232. https://doi.org/10.1249/JSR.0000000000000077

[1] 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 Medicine48(7), 491–497. https://doi.org/10.1136/bjsports-2014-093502 

[1] 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 Medicine52(11), 687–697. https://doi.org/10.1136/bjsports-2018-099193

[1] 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

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

[1] 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 Metabolism102(5), 1413–1439. https://doi.org/10.1210/jc.2017-00131 

[1] 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

[1] 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