Hypothalamic amenorrhoea talk 2015

Babies, bones and body fat percentage Why worry about hypothalamic amenorrhea?

Dr Megan Ogilvie The Endocrine Group Fertility Associates

Outline • What is Hypothalamic Amenorrhea?

• Nomenclature – Female athlete triad – IOC consensus statement – REDs

• How to diagnose – PCOS vs HA

• Why should we worry?

– Bone Density – Future Fertility

• What can we do?

– Multidisciplinary approach – Timing

Too Fat Too Thin or Just Right?

Energy Deficit (Weight/ fat mass loss, reduced nutrition, exercise)

Stress (Physical or psychological)

Leptin Kisspeptins

Hypothalamus GnRH

Pituitary FSH, LH

Ovary Estrogen

Hypothalamic Amenorrhoea Suppressed gonadotropin levels/function due to: chronic energy deficit and/or psychological stress

Lawson EA and Klibanski A (2008) Endocrine abnormalities in anorexia nervosa

IOC consensus Statement: RED-S • Energy deficiency – Balance between energy intake and expenditure – No standard method for assessing energy availability

• Specific sports at high risk – Runners, cyclists, jockeys, ballet

• Possibly effects males (need more studies) – Lowered BMD – Multisystem presentation, can be subtle (Br J Sports Med 2014;48:289)

Relative Energy Deficiency in Sport (RED-S)

Mountjoy et al, Br J Sports Med 2014;48:491–497.

Anna Smith • • • •

25 year old woman Secondary amenorrhea 9 months Regular periods prior What will you ask her: – No acne, hirsutism – Busy lawyer – 60 hour weeks – Recent relationship break up – 7 hours/ week at gym, low carb diet, gluten free – BMI 21, 5 kg weight loss 1 year ago

Polycystic ovarian syndrome vs hypothalamic amenorrhea HA

PCOS – Periods weight – Androgen excess symptoms – Test, PRL, normal E2 – USS – normal endometrium

– Periods weight – Lanugo hair – E2, LH, FSH – USS – thin endometrium – Spinal osteopenia

Don’t forget a mixed picture

Robin, 2012

Assessment (What to Ask) Take your time with history – often the most informative Aim is early diagnosis and intervention  Current BMI and pattern of weight change  Period pattern with weight change  Menarchal weight  Eating and exercise patterns - specifics  What else is going on - ?psychological stressors

Assessment (What to Measure) Weight, BMI, waist circumference LH, FSH and estradiol levels – FSH 5.4 LH 1 E2 <150 Prolactin, testosterone, TSH, pituitary testing Venous bicarbonate if concerned about purging Pelvic USS – thin endometrium Bone Mineral Density ?Pituitary MRI

Diagnosis o Clinical history o Less periods with energy deficit o Psychological stressors o Personality type â&#x20AC;&#x201C; Type A, goal orientated

o Investigations o Normal prolactin, TSH, T o Low LH and oestradiol o Thin endometrium o Relative spinal bone loss THINK â&#x20AC;&#x201C; hypothalamic amenorrhea

Why Worry?

• Serious end points without intervention: – Clinical eating disorders – Osteoporosis – Infertility

• Physical and emotional well being – Decreased physical performance, injury rate – Decreased cognitive performance

• Endothelial dysfunction due to low oestrogen • High cortisol levels, low IGF1, low T

Effects on Bone • 90% of peak bone mass attained by 18 years • Advantage of weight bearing exercise on bone lost in amenorrheic athletes • Relative spinal BMD loss often seen • Continued amenorrhea – 2-3% loss bone mass/year • OCP ineffective • Transdermal oestrogen possibly

Effects on Fertility • Infertility: anovulatory cycles and shortened luteal phase • Reduced response to treatment: possible reduced pregnancy rates to IVF and increased miscarriage rate

• Adverse pregnancy outcomes: higher risks of pre-term birth and low birth weight

Prevalence of subtle menstrual disturbances among sedentary and exercising volunteers Assessed by daily hormone levels A = sedentary women BMI 22.7 =/- 0.9 < 2 hr/week 100% regular periods

B = exercising women BMI 21.3 =/- 0.2 Purposeful exercise > 2 hr/week 7% oligomenorrheic 37% amenorrheic

De Souza M et al. Hum. Reprod. 2010;25:491-503 Š The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Association between hours of vigorous physical activity per week and fecundability (BMI < 25)

Women age 18 â&#x20AC;&#x201C; 40 yrs Self report of physical activity 12 month study Relationship preserved even when excluding women with BMI < 18.5

Wise et al. Fertil Steril. 2012 May;97(5):1136-42.

Lifestyle Management

Key to the reversal of all complications Multidisciplinary approach: – – – – – – –

Specialist and GP Sports physician Nursing support Dietician Psychologist – CBT/hypnotherapy Psychiatrist Eating Disorder Unit (urgent: BMI<15.5, >4kg in 6/52, medical complications)

Lifestyle Management Need to find a reason relevant to the patient to reverse The art of negotiation

Adequate nutrition and maintenance of BMI within the ‘normal’ range (> 22) Reduce exercise (at least 1 ‘rest day’ per week) Minimise high impact exercise as much as possible

Keep addressing the anxiety caused by changes

It can take 9-12 months of stable weight before menstruation resumes The weight needed for restoration of menses is typically higher than the weight at which menses was lost Discuss body “burn out” Warn that fertility may return quickly Monitor gonadotropins – LH increases first Unclear why some respond quickly – May be a genetic contribution

Take Home Messages Common diagnosis with the potential for long term complications Think about energy balance, not just BMI Limit cardiovascular exercise fuel for exercise Often multifactorial cause so discuss the issues and get support early (be alert to disordered eating) Aim for a multidisciplinary approach

CBT and FHA • 20-week randomized trial CBT vs Ob • 16 normal-weight women BMI 21-23 • < 10 hours exercise/week, no psychiatric diagnosis • 16 CBT sessions – Healthy eating, exercise – Problem solving and coping skills – Body image

• Ovulation returned in 6/8 (CBT) vs 1/8(observation) BMI unchanged Berga et al. Fertil Steril 2003;80:976-981.

Performance consequences of RED-S

Mountjoy et al, Br J Sports Med 2014;48:491â&#x20AC;&#x201C;497.

The Female Athlete Triad

De Souza M J et al. Br J Sports Med 2014;48:289

Copyright Š BMJ Publishing Group Ltd & British Association of Sport and Exercise Medicine. All rights reserved.