• Dr. Paul Raas

Young Women without Periods and Bone Health

Young Women without Periods and Bone Health

Functional Hypothalamic Amenorrhoea



INTRODUCTION




Amenorrhoea means not having any periods. Hypothalamic means that the root cause lies in the Hypothalamus, a brain structure that links your hormone system with your central nervous system.

This condition has many harmful consequences, one of the most important being BONE LOSS, leading to at least a two-fold increase of fractures compared to healthy, menstruating women.




CAUSE


Negative energy conditions with weight loss, as we see in Anorexia or even without weight loss, as we observe in excessive physical training.

Psychological stress is also a common cause of Functional Hypothalamic Amenorrhoea.

Regardless of which cause, FHA harms the bones, diminishing Bone Density and resulting in higher fracture rates.



WHY?


Bones are tissue. Very much alive and showing continuous growth and resorption.

Hormonal and non-hormonal regulatory influences carefully regulate it.

Balanced bone metabolism is crucial for your health. Disturbances, where resorption is greater than growth, will eventually lead to the development of chronic diseases, such as Osteopenia (Bone Loss) and eventually Osteoporosis (fragile bones, more likely to break). A condition which can be pretty debilitating.


Exercise in healthy women will benefit bone health. Excessive exercise, on the contrary, when resulting in amenorrhoea, can lead to bone loss.



Lifetime fracture risk was almost double compared to athletes with regular periods and four-fold higher compared to non-athletes. The bone structure was negatively affected.


Anorexia Nervosa, often called anorexia — is an eating disorder characterised by abnormally low body weight, an intense fear of gaining weight and a distorted perception of weight. People with anorexia place a high value on controlling their weight and shape, using extreme efforts that significantly interfere with their lives.


(https://www.mayoclinic.org/diseases-conditions/anorexia-nervosa)


There is abundant evidence for low bone density and fracture risk in this condition.

Anorexia Nervosa is predominantly seen in younger women, typically in adolescence. At a time when bones should reach their maximum strength and density. Furthermore, this increased risk persists ten years from diagnosis, suggesting irreversible bone impairment if not treated early.



Chronic starvation will eventually result in increased bone resorption and decreased bone growth due to hormone dysregulation (sex hormones, thyroid hormones, appetite hormones, growth hormones and adrenal hormones).

Cells that make bone, will be replaced by fat cells forming Bone Marrow Adipose Tissue, resulting in less bone production.

Malnutrition will lead to low sodium levels and low dietary calcium intake.

Changes in the Gut Microbiota might also contribute to the process of bone loss.


Psychological stress is an under-appreciated but important cause of amenorrhoea.

Women without periods showed a significant drive for thinness and a greater need for social approval than women having regular menstrual cycles.

Furthermore, this was positively associated with indicators of psychological stress and depression.


Generally, women with amenorrhoea have more dysfunctional attitudes (such as a drive for perfectionism, rigidity of ideas, preoccupation of being judged), more depressive symptoms and less able to cope with stressors.


TREATMENT


Weight gain, restoration of energy balance and reduction in psychological stress leading to restoration of menstrual cycles are the most effective management strategies for amenorrhoea-related bone loss.

Unfortunately, on the long haul, this is challenging for most women with Functional Hypothalamic Amenorrhoea, making it necessary finding other strategies to protect their bone health.


Oestrogen (17 beta-estradiol) replacement, compensating its deficit, showed remarkable positive results, especially when administrated transdermal.



Oral contraceptives containing the potent oestrogen Ethinyl Estradiol (EE) regretfully did not produce the same positive results.

Further studies are required to clarify the independent benefits of androgen treatment and IGF1 treatment.


Leptin treatment was associated with approximately 3% weight loss, which has ultimately restricted its development for FHA, despite promising results.

An anabolic agent treatment (Teriparatide) for 24 months resulted in a significant increase in bone density. Barriers to the use of Teriparatide are its limited use of up to 2 years, cost and the inconvenience of daily injections.


Future pharmaceutical avenues include the monoclonal antibody (Romosozumab), which is approved for the treatment of postmenopausal Osteoporosis.


Another recent promising avenue is a recently developed hormonal treatment (Kisspeptin). Kisspeptin administration can restore regular menstrual cycles. At the same time, twice-weekly injections for eight weeks can stimulate the secretion of reproductive hormones. Recent data have emerged, suggesting that Kisspeptin administration can also have direct positive effects on human bones.


Currently, the data point to transdermal oestrogen replacement as the optimal strategy.



Literature: Behary P and Comninos AN (June 2022)

Bone Perspectives in Functional Hypothalamic Amenorrhoea: An Update and Future Avenues.

Front. Endocrinol. 13:923791.

doi: 10.3389/fendo.2022.923791


Dr. Paul Raas

PROFEMINA