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.