The influence of estrogen deficiency in physically active women with functional hypothalamic amenorrhea (ExFHA) on cardiovascular regulation is unknown. Three mechanistic studies compared cardiovascular responses to exercise and orthostatic stress in ExFHA women with responses in physically active (ExOv) and sedentary (SedOv) eumenorrheic ovulatory women. Measures included calf blood flow (BF), brachial artery (BA) endothelial dependent and independent function, shear rate (SR), vascular resistance (VR), blood pressure (BP), heart rate (HR), HR variability (HRV), muscle sympathetic nervous activity (MSNA), and serum renin-angiotensin-aldosterone system (RAAS) components. Study one examined the effects of a single bout of dynamic exercise on vascular function in ExFHA (n=12), ExOv (n=14), and SedOv (n=15) women. Pre-exercise, calf BF and BA endothelium-dependent flow-mediated vasodilation (FMD%) were lower (p<0.05) in ExFHA versus ovulatory women in association with higher (p<0.05) calf VR and lower (p<0.05) SR, respectively. Endothelium-independent vasodilation, assessed at baseline only, was also lower (p<0.05) in ExFHA. Post-exercise, calf BF was increased and VR decreased (p<0.05) in ExFHA women, similar (p>0.05) to that observed in ovulatory women. FMD% and SR were augmented (p<0.05) post-exercise, but both remained lower (p<0.05) in ExFHA versus ovulatory women (p<0.05). Study two investigated neurohumoral (MSNA and RAAS) BP regulation during orthostatic stress in ExFHA (n=12) and ExOv (n=17) women. Baseline systolic BP was lower (p<0.05) in ExFHA versus ExOv. Neurohumoral measures did not differ (p>0.05) between the groups at baseline. However, during hypotensive stimuli, MSNA increased to a greater extent (p<0.05), yet angiotensin II and renin were not activated in ExFHA women. Study three examined autonomic control of HR during orthostatic stress in ExFHA (n=11), ExOv (n=17), and SedOv (n=17) women. Lower HR (p<0.05) at rest and during orthostatic stress in ExFHA was associated with markedly elevated (p<0.05) HRV due to higher (p<0.05) parasympathetic modulation. Sympathetic modulation did not differ (p>0.05) between the groups. These studies indicate altered cardiovascular regulation in otherwise healthy ExFHA women. The influence of estrogen deficiency per se in these alterations are not clear, but in light of the etiology of amenorrhea, it is likely that complex interactions between estrogen and energy deficiency and exercise training are involved.

The influence of estrogen deficiency in physically active women with functional hypothalamic amenorrhea (ExFHA) on cardiovascular regulation is unknown. Three mechanistic studies compared cardiovascular responses to exercise and orthostatic stress in ExFHA women with responses in physically active (ExOv) and sedentary (SedOv) eumenorrheic ovulatory women. Measures included calf blood flow (BF), brachial artery (BA) endothelial dependent and independent function, shear rate (SR), vascular resistance (VR), blood pressure (BP), heart rate (HR), HR variability (HRV), muscle sympathetic nervous activity (MSNA), and serum renin-angiotensin-aldosterone system (RAAS) components. Study one examined the effects of a single bout of dynamic exercise on vascular function in ExFHA (n=12), ExOv (n=14), and SedOv (n=15) women. Pre-exercise, calf BF and BA endothelium-dependent flow-mediated vasodilation (FMD%) were lower (p<0.05) in ExFHA versus ovulatory women in association with higher (p<0.05) calf VR and lower (p<0.05) SR, respectively. Endothelium-independent vasodilation, assessed at baseline only, was also lower (p<0.05) in ExFHA. Post-exercise, calf BF was increased and VR decreased (p<0.05) in ExFHA women, similar (p>0.05) to that observed in ovulatory women. FMD% and SR were augmented (p<0.05) post-exercise, but both remained lower (p<0.05) in ExFHA versus ovulatory women (p<0.05). Study two investigated neurohumoral (MSNA and RAAS) BP regulation during orthostatic stress in ExFHA (n=12) and ExOv (n=17) women. Baseline systolic BP was lower (p<0.05) in ExFHA versus ExOv. Neurohumoral measures did not differ (p>0.05) between the groups at baseline. However, during hypotensive stimuli, MSNA increased to a greater extent (p<0.05), yet angiotensin II and renin were not activated in ExFHA women. Study three examined autonomic control of HR during orthostatic stress in ExFHA (n=11), ExOv (n=17), and SedOv (n=17) women. Lower HR (p<0.05) at rest and during orthostatic stress in ExFHA was associated with markedly elevated (p<0.05) HRV due to higher (p<0.05) parasympathetic modulation. Sympathetic modulation did not differ (p>0.05) between the groups. These studies indicate altered cardiovascular regulation in otherwise healthy ExFHA women. The influence of estrogen deficiency per se in these alterations are not clear, but in light of the etiology of amenorrhea, it is likely that complex interactions between estrogen and energy deficiency and exercise training are involved.

Bakgrund: Ett av sex par har någon gång upplevt problem relaterat till fertilitet under sina reproduktiva år och efter 30 års ålder är infertilitet vanligare hos kvinnor än hos män. Flera delar av menstruationscykeln består av energikrävande processer som exempelvis ägglossning och produktion av könshormoner. Näringsbrist och låg energitillgänglighet leder till brist på substrat till dessa energikrävande processer och i västvärlden orsakas låg energitillgänglighet vanligen av en ätstörning som anorexia nervosa, vilket kan leda till funktionell hypotalamisk amenorré (FHA) hos kvinnor. FHA resulterar i en minskad frisättning av könshormonerna östrogen och progesteron vilket kan leda till infertilitet. En av 20 kvinnor har erfarenhet av ätstörning under graviditeten men få studier har undersökt hur en historik med ätstörning påverkar fertilitet och graviditet. Syfte: Syftet med studien var att undersöka om FHA hos kvinnor med anoreci leder till nedsatt fertilitet och komplikationer vid en eventuell graviditet. Metod: En litteratursökning genomfördes på PubMed och Web of Science med sökorden amenorrhea, fertility, eating disorders, anorexia nervosa, reproduction (1999-2021). Resultat: Åtta studier inkluderades och resultatet visade att kvinnor med anorexi födde färre barn och hade större sannolikhet för att ha genomgått fertilitetsbehandling än friska kvinnor i kontrollgruppen. Vidare visade resultatet att kvinnor med anorexi oftare rapporterade komplicerade graviditeter med till exempel lägre fostertillväxt, prematur födsel och kejsarsnitt. Slutsats: Utifrån resultatet i den aktuella litteraturstudien kan konkluderas att kvinnor med FHA på grund av en ätstörning har lägre fertilitet än friska kvinnor. Kvinnor med ätstörning upplever i högre utsträckning mer komplicerade graviditeter och även fosterutvecklingen verkar påverkas negativt och därför kan tätare kontroller under och efter graviditet vara nödvändigt för dessa kvinnor. Resultatet kan vidare tolkas som att den negativa påverkan på reproduktionsförmågan kan vara reversibel när ätstörninssymptomen behandlats. / Background: One in six couples has sometime during their reproductive years experienced problems related to fertility and after the age of 30, infertility is more common in somen than in men. Several parts of the menstrual cycle require a lot of energy, such as ovulation and the production of sex hormones. Malnutrition and low energy availability is usually caused by an eating disorder such as anorexia nervosa, which can lead to functional hypothalamic amenorrhea (FHA) in women. FHA leads to a reduced release of the sex hormones estrogene and progesterone, which leads to infertility. One in 20 women have experience of an eating disorder during pregnancy, but few studies have examined how a history og eating disorder affects fertility and pregnancy. Aim: The aim of this study was to investigate whether FHA in women with anorexia nervosa leads to reduced fertility and complications in a potential pregnancy.  Method: A literature search was made on PubMed and Web of Science with the keyword´s amenorrhea, fertility, eating disorders, anorexia nervosa reproduction (1999-2021). Results: Eight studies were included, and the results showed that women with anorexia gave birth to fewer children and were more likely to have experienced fertility treatment than healthy women in the control group. Furthermore, the results showed that women with anorexia more often reported more complicated pregnancies with, e.g., lower fetal growth, premature birth, and cesarean section. Conclusion: Based on the results of the current literature study, it can be concluded that women with FHA due to an eating disorder have lower fertility than healthy women. Women with an eating disorder experience more complicated pregnancies and fetal development also seems to be negatively affected and therefore more frequent checks during and after pregnancy may be necessary fore these women. The results can further be interpreted as that the negative impact on reproductive health is reversible when symptoms of eating disorder are treated.