Subclinical Ovulatory Disturbances

Adaptation of menstrual cycle hormones

In my book “Hormones, Health and Human Potential”, I really enjoyed writing the chapter 5XX “Of Mice and men….and Women!” Celebrating Horme the goddess of effort, energy and action. However, there are some instances where even this formidable goddess is challenged and adaptations are required[1].

Challenges to menstrual cycle hormones

Menstrual cycle hormone choreography is as beautiful as it is complex. Generally, this repeating motif follows the score faithfully during a woman’s reproductive years. However, when external stressors become too great, then menstrual hormone fluctuations respond and adapt.

A single stressor, for example financial concerns or a life event can impact hormones and disrupt menstrual cycles on a short time scale of a handful of cycles. However, a combination of stressors can have a synergistic effect on disrupting female hormone networks. Additive stressors over a long-time scale are known as an allostatic load. A high allostatic load causes a more extensive adaptation of female hormones[2]. For example, a high level of stress from intense exercise training together with metabolic stress from insufficient food intake can result in total suppression of menstrual cycle hormone fluctuation and cessation of periods (amenorrhoea) found in relative energy deficiency in sport (RED-S).

Unbalanced behaviours

Although “hormone imbalance” is a popular phrase, this has no medical meaning. This misleading phrase does a massive disservice to Horme and to millions of years of evolution in fine-tuning the most intricate hormone network. It is not the hormone network that has become “unbalanced”, rather it is our unbalanced behaviours and/or management of external stressors that have caused hormones to adapt and change appropriately. On a positive note, understanding hormones empowers us to nurture and harness our hormones through our lifestyle choices.  

Spectrum of female hormone adaptation

There is a graded response of female hormones to external stressors, depending on the number and the time scale of these. A cumulative combination of stressors results in a high allostatic load which causes amenorrhoea. Physiological causes of amenorrhoea must be excluded: pregnancy and menopause; as should medical causes such as prolactinoma and polycystic ovary syndrome (PCOS).

The type of amenorrhoea occurring as an adaptive response to a high allostatic load is functional hypothalamic amenorrhoea (FHA). This means that the neuroendocrine gatekeeper in the brain, the hypothalamus, has taken the executive decision to suspend female hormone fluctuations, in order to conserve resources to deal with the stressful situation. From an evolutionary point of view this is not the time for the high demand state of pregnancy. The good news is that being an adaptive functional response, FHA is reversible if the underlying cause is addressed.

Tip of the iceberg

Amenorrhoea is a very obvious clinical sign. Similarly, oligomenorrhoea (less than 9 periods per calendar year). However, these menstrual disruptions are just the tip of the iceberg. Less obvious are the subclinical ovulatory disturbances (rather unflatteringly referred to as SODs). This is where a women may experience a menstrual period, but the full repertoire of female hormone fluctuation has not occurred. Specifically, progesterone has not increased to levels that would be expected in the luteal phase of the cycle (second half of the cycle). If ovulation has occurred, then the remnant of the egg follicle in the ovary forms the corpus luteum which secretes progesterone. Progesterone increases resting metabolic rate and energy demand. So, keeping progesterone low is a good adaptive response to high allostatic load by keeping energy demand low.

If subclinical ovulatory disturbances are an adaptive physiological response, does this matter for a woman’s health? The answer is yes. Oestradiol (the most active form of oestrogen) often takes the limelight when it comes to positive effects on bone, soft tissue, cardiovascular, and neurological health. However, evidence is emerging that progesterone plays an equally important supporting role in these areas of health. For this reason, it is important to identify these elusive disturbances in menstrual hormone choreography.

How to detect subclinical ovulatory disturbances

As I discuss in my book in the chapter “Hormone Supermodels”, applying artificial intelligence (AI) techniques to modelling menstrual cycle hormones can help in identifying subtleties in hormone disruption. This is a fast-moving field and even since publishing on this topic, further advances are being made as more data is emerging and employment of different mathematical techniques, with reduction in the number of samples required. Monitoring temperature change as surrogate for indicating adequate progesterone levels during the luteal phase is a non invasive way of monitoring menstrual cycle hormone function. Personalisation of female hormone health is on the move. Nevertheless, the cornerstone of any medical AI focused on hormones is the medical doctor with expertise in hormones, putting the results in clinical context for the individual. Explaining and advising with practicality and empathy is vital.

This personalised medical approach is crucial when, by definition, subclinical ovulatory disturbances will require guidance on changing behaviours to reverse adaptive hormone changes. When I work with athletes and dancers experiencing hormone disruption due to imbalances in exercise and nutrition, I find it helpful in referring to recovery from a hormone injury as comparable to recovering from a physical injury. Furthermore, there can be a psychological dimension to subclinical ovulatory disturbances. How we interpret external events and think impact our hormones. For example, cognitive dietary restraint (just thinking you should eat less/be thinner) can cause subclinical ovulatory disturbances.

Nurturing Horme

Menstrual cycle hormone choreography is the most intricate and beautiful of all the hormone networks. There is a spectrum of hormone adaptation according to the degree of “stress” put on the system. The visible tip of the iceburg is menstrual disruption such as amenorrhoea and oligomenorrhoea. Less obvious, beneath the surface are subclinical ovulatory disturbances. Subclinical ovulatory disturbances are adaptive hormone responses to unbalanced behaviours and/or interpretation of external events. These subtleties of subclinical ovulatory disturbances can be challenging to identify. However, it is important to do so and provide appropriate medical support to restore these hormones for long term health.

[1] Keay N. Hormones, Health and Human Potential 2022 Sequoia books

[2] Prior J. Adaptive, reversible, hypothalamic reproductive suppression: More than functional hypothalamic amenorrhea Front. Endocrinol 2022 Sec. Reproduction

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