The following is adapted from a case presented in the European
Journal of Endocrinology in 2006.
...A 15.5-year-old girl presented for evaluation of obesity and
amenorrhea.
The patient started a marked weight gain from 8 years of
age...Menarche (the first menstrual period) occurred at the age
of 14, but soon thereafter, she stopped menstruating.
What is meant by the term "amenorrhea"?
The patient was obese; her height was 160.8 cm...weight 83.0
kg...body mass index (BMI) 32.1 kg/m2, waist
circumference 85 cm, and blood pressure 135/84...The patient was
hirsute...and had mild acne.
What is meant by the term "hirsute"?
Hirsutism and acne are clinical evidence of what endocrine disturbance?
Serum testosterone and luteinizing hormone levels were elevated,
while follicle-stimulated hormone, estradiol, and 17-OH
progesterone levels remained normal (see table). Baseline serum
thyroid-stimulating hormone, free thyroxine, prolactin, and 24-h
free urinary cortisol were within normal limits.
| Variable |
Patient Value |
Reference Range |
|---|---|---|
| Follicle-stimulating hormone
(U/L) |
5.9 | 3.3-6.06 |
| Luteinizing hormone (U/L) |
11.0 |
4.8-10.73 |
| Testosterone (nmol/L) |
4.3 |
0.42-2.05 |
| Estradiol (nmol/L) |
0.18 |
0.143-0.324 |
| 17-OH progesterone (nmol/L) |
2.8 |
<4.4 |
...Pelvic ultrasound showed bilateral polycystic ovaries.
Based on the clinical and biochemical evidence of
hyperandrogenism, ovulatory dysfunction, and polycystic ovaries,
this patient was diagnosed with polycystic
ovary syndrome (PCOS).
In this patient, ovulatory dysfunction is clearly indicated by
amenorrhea. Some women with PCOS may present with abnormal uterine bleeding,
defined as cycles that are longer than 38 days, shorter than 21
days, or characterized by excessive menstrual bleeding.
However, menstrual cycles tend to be irregular during adolescence,
and many times doctors are slow to suspect that an adolescent
patient could have ovulatory dysfunction and PCOS.
An important step in establishing a diagnosis of PCOS is to rule out other potential causes of hyperandrogenism and amenorrhea. The 17-OH progesterone level is measured in order to rule out congenital adrenal hyperplasia, a disorder that is usually caused by a defect in an enzyme involved in cortisol synthesis, and that results in excessive androgen production by the adrenal gland. TSH and thyroxine are measured in order to rule out hypothyroidism, which also can cause amenorrhea. Prolactin is measured in order to rule out hyperprolactinemia, another major cause of amenorrhea.
Below are the measures obtained during an oral glucose tolerance
test.
| Time (hours after glucose
dose) |
0 |
1 |
2 |
| glucose (mg/dL) |
110* | 184 | 164* |
| insulin (mIU/L) |
37.0✝ |
113.6 | 117.8 |
| *Normal fasting glucose (at time 0) should be
<100mg/dL and 2 hour glucose in an oral glucose
tolerance test should be <140 mg/dL. Impaired
glucose tolerance is defined as any reading above
200 mg/dL or a 2 hour reading >140 mg/dL. ✝Reference range for fasting insulin is <25mIU/L. |
This patient has impaired glucose tolerance, indicating that she is insulin resistant. What is the other sign that she has insulin resistance?
The goal of treatment in an adolescent with polycystic ovary
syndrome is to control symptoms of hyperandrogenism and menstrual
dysfunction. In this patient, who is obese and insulin
resistant, there is also an increased risk for the development of
type 2 diabetes mellitus.
This patient was treated with metformin,
a drug that improves insulin sensitivity. She was also advised to
alter her diet and increase physical activity so as to lose
weight.
After 1 year on treatment, weight was 70.8 kg and BMI 27.3 kg/m2.
Fasting glucose and insulin levels were normal...Polycystic
ovaries remained, but menses were now normal ovulatory menstrual
cycles...
What is the effect of insulin on the ovary?
Why do you suppose treatment with metformin (and weight loss) resulted in normal menstrual cycles?
In this patient, treatment with metformin was able to successfully restore regular menstrual cycles. What is the usual first-line treatment to address menstrual irregularity and hyperandrogenism in a woman with PCOS who does not want to conceive?
Review the webpage: Polycystic ovary syndrome
For those who are interested in reading the original paper, the
reference is:
Ojaniemi, M. and Pugeat, M. (2006) "An adolescent with
polycystic ovary syndrome" European Journal of Endocrinology 155:
S149-S152 (link)