Hypothalamic Amenorrhea Part 2: Consequences of HA

Although not having a period & all the not-so-lovely symptoms that come with it (cramps, mood swings, fatigue, etc.) may seem wonderful- a regular menstrual cycle is a vital sign of good health. Without a healthy cycle, we can run into irreversible health consequences and thus it’s important to address the root cause with a professional when we find out periods go missing.

1. Bone loss

Evaluation of BMD by a DEXA scan is recommended for adolescents or women who have had amenorrhea for 6 months or longer. Estrogen stimulates osteoblast activities and acts as a promoter of growth factors (e.g. insulin-like growth factor and bone morphogenetic protein 6). In a hypoestrogenic state, osteoblasts undergo apoptosis and osteoclastic (bone resorption) activity is stimulated by decreasing the gene expression of osteoprotegerin (an inhibitor of osteoclast formation). Thus, HA increases the risk of developing early osteopenia or osteoporosis which then increases the risk of bone fractures.

 Risk factors for low BMD include an underweight body mass index (BMI), low weight, lean body mass (BM), low body fat and later menarche. Insufficient caloric intake and malnutrition will result in nutritional deficiencies (including calcium, magnesium and vitamin D intake) that are essential for bone metabolism. In addition, hormonal disturbances (including low estrogen, DHEA and testosterone) that occur as a response to long-term energy deprivation will inhibit bone mass accrual/increase BMD loss. Other hormonal changes associated (such as reduced thyroid levels, and increased cortisol levels) will further inhibit BMD accrual.   

  Unfortunately, the oral contraceptive pill (OCP) will not protect against bone loss and it is strongly recommended to address the root cause/s of HA and regain natural menstrual cycles without the pill. Bisphosphonates are not recommended for women of reproductive age as this could later affect the foetal skeleton in pregnancy. Short-term transdermal estrogen may be more beneficial to individuals with chronic amenorrhea as this is safer & more bioavailable to the bone. However, it is important to attempt the restoration of menses naturally as this will help to increase bone mass density (BMD). 

 2. Cardiovascular disease

Endogenous estrogen has cardiovascular protective effects and when the body is in a hypoestrogenic state, this impairs the endothelial function, impairs liver function and prevents normal blood vessel vasodilation. Estrogen acts as a vasodilator, reduces vascular inflammation, lowers LDL cholesterol prevents endothelial dysfunction and reduces oxidative stress. Irregular menstruation cycles have also been associated with early menopause (menopause under 45 years) which further increases their risk for cardiovascular events.

As HA is a hypoestrogenic state, HA increases the risk for premature cardiovascular events and atherosclerosis.

3. Hypothyroidism

In long-term restrictive eating, the body may adapt to the low energy availability, suppress its thyroid function and reduce the active thyroid hormones T3 & T4 which then reduces the basal metabolic rate (BMR). This will impair bone formation and retard growth which will contribute to further bone loss. However, thyroid gland abnormalities usually are reversed with proper nutrition.

4. Dry & weak skin, hair & nails

Vitamin and mineral deficiencies (such as biotin, zinc, omega-3 fatty acids and magnesium) as a result of insufficient caloric intake will cause abnormalities in the skin, hair and nails and these can include thinning hair, dry and brittle nails and dry skin. Seeking assistance from a nutritionist is important to address potential nutritional deficiencies.

5. Loss of libido & vaginal dryness

Sexual dysfunction occurs commonly in those with HA due to the hypoestrogenic state. It has been consistently reported individuals with HA experience mood disorders, depression and anxiety. Individuals with depression and anxiety have been shown to report reduced sexual desire, arousal and satisfaction compared to functional women.  

 6. Digestive complaints

Long-term food restriction can cause atrophy of the gastrointestinal muscles and lead to delayed gastric emptying (‘gastroparesis’) resulting in feelings of fullness after eating a small amount, constipation, bloating, flatulence and abdominal pain. The body will also slow down digestion in an attempt to absorb as much of the nutrients and calories consumed. Other possible causes of gastrointestinal discomfort after restricted food intake includes suppressed thyroid function, decreased stomach acid, reduced stomach acid, and micronutrient deficiencies. 

In addition, consuming excess dietary fibre, ‘sugar-free’ products, chewing gum and psychological stress can worsen gastrointestinal symptoms.

7. Mood disorders (including anxiety, depression, irritability, etc.)

A bidirectional relationship often exists between HA and mood disorders with women with HA have a significantly higher risk for depression, anxiety, elevated cortisol levels and poor stress coping skills

 Furthermore, often women will HA will also present perfectionist tendencies (“type A personality traits), and disordered eating patterns and exhibit greater fixation on their weight and appearance compared to eumenorrhea controls. Other common psychological and mental concerns exhibited commonly in women with HA are feelings of anxiety, insecurity and inadequacy.

8. Lowered fertility

In women with HA, ovulation cannot occur, the endometrial cannot thicken and thus fertilisation of an egg will be difficult. Whilst HA is a functional condition and reversible, if left untreated over a prolonged period it can affect future female reproductive health. HA can decrease vaginal lubrication, thin the endometrium, and atrophies the urogenital mucosa and uterus.

Furthermore, underweight or low BMI will increase the risk for high-risk delivery, miscarriage and preterm delivery (delivery before 37 weeks).

9. Lower leptin levels & increased ghrelin levels

Leptin is a hunger hormone and an appetite regular. Low leptin levels are caused by chronic energy (kJ) deficiency and low-fat mass resulting in reduced GnRH secretion. Ghrelin is a ‘hunger hormone that stimulates appetite but decreases fat utilisation. In individuals with HA, Leptin levels will be considerably lower and ghrelin levels considerably higher compared to non-HA individuals when controlled for weight and body fat. 

 10. Neuroinflammation 

Lowered estrogen levels and elevated cortisol levels have been linked to a possible increase in impaired cognitive function and accelerating aging syndromes. This may increase the risk of developing neurodegenerative disease and premature brain aging. 

Final word

This post isn’t intended to be all dark & gloomy but it is to inform on the importance of having a cycle. There ARE resources available & support to get the help you need. This condition is treatable & the time to recovery could be as short as a few weeks to years depending on how your hormones, body & readiness to recover. Please see part 3 for how to heal from HA.

REFERENCES 

Usdan, L., Khaodhiar, L., & Apovian, C. (2008). The Endocrinopathies of Anorexia Nervosa. Endocrine Practice, 14(8), 1055-1063. doi: 10.4158/ep.14.8.1055

 Meczekalski, B., Katulski, K., Czyzyk, A., Podfigurna-Stopa, A., & Maciejewska-Jeske, M. (2014). Functional hypothalamic amenorrhea and its influence on women’s health. Journal Of Endocrinological Investigation, 37(11), 1049-1056. doi: 10.1007/s40618-014-0169-3

Prokai, D., & Berga, S. (2016). Neuroprotection via Reduction in Stress: Altered Menstrual Patterns as a Marker for Stress and Implications for Long-Term Neurologic Health in Women. International Journal Of Molecular Sciences, 17(12), 2147. doi: 10.3390/ijms17122147

Seaborg, E. (2017). Functional Hypothalamic Amenorrhea Treatment Guidelines. Retrieved 28 September 2020, from https://endocrinenews.endocrine.org/no-easy-answers-new-hypothalamic-amenorrhea-treatment-guidelines/

Tranoulis, A., Georgiou, D., Soldatou, A., Triantafyllidi, V., Loutradis, D., & Michala, L. (2019). Poor sleep and high anxiety levels in women with functional hypothalamic amenorrhoea: A wake-up call for physicians?. European Journal Of Obstetrics & Gynecology And Reproductive Biology: X, 3, 100035. doi: 10.1016/j.eurox.2019.100035