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Diagnostic Evaluation of Amenorrhoea Related to Weight Control
with low T3 levels, reducing hepatic protein synthesis (in particular Figure 1: Chronic Stress Response
insulin-like growth factor 1 [IGF-1]). Low IGF-1 levels are uncoupled
with growth hormone (GH) levels, which are generally normal. Thus, in
Hypothalamus
subjects with amenorrhoea related to weight control, serum LH
levels, free T3 and IGF-1 are low or in the lower reference range, while
mean concentration of cortisol tends to exceed the standard range,
AVP
especially when measured in the evening.
Autonomic nervous system CRF
GnRH
Two hormones, the levels of which are directly related to energy
FSH, LH
availability, can be useful diagnostic tools: these are leptin and insulin.
ACTH
T
4
metabolism
Leptin is traditionally considered to be a connecting signal between
fat stores and reproductive function, with a threshold effect on Leukocytes and
gonadotropin production mediated by hypothalamic kisspeptin
acute-phase proteins
Ovary Cortisol
neurons.
11
A direct effect of leptin has been demonstrated by
administering recombinant metHuLeptin at replacement doses to
Dotted arrows = inhibition; continuous arrows = stimulation.
AVP = arginine vasopressin; CRF = corticotrophin-releasing factor;
women with hypothalamic amenorrhoea related to strenuous GnRH = gonadotrophin-releasing hormone; FSH = follicle-stimulating hormone;
exercise or low weight: this treatment rapidly improved LH pulse
ACTH = adrenocorticotrophic hormone.
frequency and mean concentrations as well as ovarian volume and
Figure 2: Biochemical Parameters Associated with
function.
12
Insulin is a key hormone in regulating short-term energy
Menstrual Recovery
homeostasis and long-term responses to energy deprivation states,
and undoubtedly plays a role in the link between metabolic state and
1.29
reproductive function.
13
In the presence of normal plasma glucose
Leptin
concentrations, fasting insulin levels close to the lower range indicate
1.46
Insulin
a situation of saving nutritional substrates.
1
Cortisol
Current research is studying the role of gastrointestinal peptides in
situations of weight control. High levels of ghrelin, a peptide of 28
1.07
FT4
amino acids synthesised predominantly by the stomach and the gut
1.15
that activates the type 1a growth hormone (GH) receptor but also
FT3
stimulates feeding behaviour and osteoblast function, have been 1.17
demonstrated in subjects with energy restraint.
14
Increased plasma
LH
levels of peptide YY (PYY), an anorexigenic peptide derived primarily
0.75
FSH
from the intestine that also plays a role in regulating bone mass, have
also been demonstrated.
15
The possibility of using these markers in a
1.97
TSH
clinical setting for the differential diagnosis of amenorrhoea is a
0 1 234
hypothesis still under discussion.
Comparison between 35 young women who resumed menses after weight rehabilitation and
The diagnostic work-up cannot be complete without a psychological 43 young women who remained amenorrhoeic after reaching a normal body mass index
evaluation. A number of tools have been validated for the screening
(BMI) for age. Data from univariate logistic regression analyses (odds ratio [OR] and 95%
confidence interval [CI]).
20
of subclinical eating disorders: the most widely-used are the Eating FT4 = free thyroxine; FT3 = free triiodothyronine; LH = luteinising hormone;
Attitude Test (EAT-26)
16
and the Eating Disorders Inventory (EDI 1 and
FSH = follicle-stimulating hormone; TSH = thyroid-stimulating hormone.
2),
17
which are generally used in the form of semi-structured clinical
interviews. Their use as self-reporting measurements of the Weight at the last menstruation preceding amenorrhoea is an
psychological factors shown to be clinically relevant in weight control important individual parameter to be considered: subjects whose
is more debatable. eating disorders commenced while they were overweight require a
slightly higher target weight for the reactivation of menstrual
For diagnostic purposes, an in-depth approach is necessary: one or function.
18
With regard to body composition, an increase in body fat
more consultations with a psychologist trained in this field are and the normalisation of the ratio of body fat to lean body mass
important for evaluating the need for psychotherapy aimed at (about 1:3, although with differences related to the method used for
analysing the roots of the disturbances, motivating changes in eating calculation) are also prerequisites for the recovery of menstrual
habits and helping to cope with the resistance to treatment. function. The recovery of bone mineral density is very slow, even
when facilitated by the achievement of endocrine equilibrium:
19
it may
Diagnostic Markers for the Recovery Phase take several years after the resumption of menses.
The main resources for the resolution of menstrual disorders related
to weight control are nutritional rehabilitation, a reduction of physical Turning our attention to endocrine markers, the normalisation of
activity where this is strenuous and, if necessary, psychotherapeutic peripheral thyroid hormone metabolism, frequently linked to a
support. How can the improvement be monitored? If weight loss is at transient increase in thyroid-stimulating hormone (TSH) dismission,
the basis of menstrual dysfunction, an increase in BMI is a and of leptin and insulin plasma levels are the base conditions for the
prerequisite for menstrual recovery, but achieving a BMI in the normal recovery of LH pulsatility, which in turn enables ovarian follicular
range for age is not always followed by a rapid resumption of menses. maturation and menstrual function
20
(see Figure 2). The normalisation
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