ANSWERS
CASE 12: EXCESSIVE HAIR GROWTH AND INFERTILITY
A 22-year-old woman presents to her GP because she is embarrassed by ‘excessive hair growth’
on her upper lip, lower abdomen and thighs. She has waxed her legs and body and shaved her upper lip weekly throughout her teenage years. On direct questioning, she reports that her periods have been irregular since menarche and that she is having difficulty conceiving despite regular unprotected sexual intercourse with her partner for the past year. Her family history is significant for diabetes and hypertension in her mother and maternal grandfather.
Examination
Physical examination reveals a mildly obese woman (body mass index [BMI] 31) with mod
erate facial acne and confirms hirsutism (Ferriman-Gallwey score 15). Examination of the genitalia is unremarkable, with a patent outflow tract and no clitoromegaly. Bimanual exam
ination reveals a mobile anteverted uterus.
INVESTIGATIONS
• FBC, renal profile: Normal
• Urine β-hCG: Negative
QUESTIONS
1. Suggest a differential diagnosis for the cause of this woman’s hirsutism.
2. Based on the clinical picture, what is the most likely diagnosis and why? What do you know about the aetiology of this condition?
3. What further investigations would be useful to confirm the likely diagnosis?
4. What are the management options in treating this woman’s symptoms and over
all condition?
5. Are there longer-term health problems that need to be considered in this patient?
DOI: 10.1201/9781003242697-13
100 Cases in Clinical Pathology and Laboratory Medicine 32
ANSWERS
Medically, hirsutism refers to excessive terminal hair growth in a male pattern in women. Up to 5% of women of reproductive age are hirsute, according to the Ferriman-Gallwey scale (which scores hair growth in the most androgen-dependent parts of the body, with a score >7 defined as hirsute). As sexual hair growth is entirely androgen-dependent, androgen levels and the sensitivity of hair follicles to androgens are the primary factors leading to hirsutism.
However, women with milder hirsutism may not show elevated androgen levels and have what is known as idiopathic hirsutism, which accounts for around 50% of cases. The remain
der of cases are associated with hyperandrogenism, the causes of which are (1) polycystic ovarian syndrome (PCOS), (2) adrenogenital syndromes (e.g., non-classic congenital adrenal hyperplasia), (3) androgen-secreting tumours, (4) other causes of hormone overproduction such as Cushing’s syndrome and (5) drug-induced.
In this woman, the main presenting complaints of hirsutism and difficulty conceiving, with probable anovulation, are consistent with a diagnosis of PCOS. PCOS affects up to 10%
of women of reproductive age and is the underlying factor in around 15–20% of infertility cases. A diagnosis of PCOS, according to the 2003 Rotterdam PCOS Consensus Group, can be made with two of the following three findings: (1) clinical or biochemical evidence of androgen excess, (2) oligovulation or anovulation and (3) polycystic ovaries on ultrasound.
The clinical findings in this case are sufficient to meet the first two of these, allowing a puta
tive diagnosis of PCOS to be made.
While the exact pathophysiology of PCOS is unclear, one theory suggests that increased gonadotrophin-releasing hormone (GnRH) pulsing leads to increased luteinising hormone (LH) pulsing, stimulating increased production of androgens by theca cells in the ovary.
There is also evidence that women with PCOS have elevated levels of insulin, which is known to act synergistically with LH to enhance androgen production by theca cells. Further, insu
lin inhibits synthesis of sex hormone–binding globulin (SHBG) by the liver, thereby increas
ing the proportion of free testosterone in the blood. These effects of insulin account for the hyperandrogenaemia in PCOS, which disrupts the normal follicular development process, leading to anovulation.
Before a diagnosis of PCOS can confidently be made, other conditions that produce hyper
androgenism and irregular menstrual cycles need to be excluded. Further investigations that may be performed to look for other causes include:
• Thyroid function (hypothyroidism)
• Serum prolactin (hyperprolactinaemia)
• 24-hour urinary cortisol (Cushing’s syndrome)
• Morning 17-hydroxyprogesterone levels (elevated in non-classic congenital adrenal hyperplasia)
• Oral glucose tolerance test and growth hormone suppression (acromegaly)
• Follicle-stimulating hormone (FSH) and oestradiol (high and low/normal, respec
tively, in premature ovarian failure)
Biochemical investigations may show increased testosterone levels, reduced SHBG, increased LH and a high LH:FSH ratio. An ovarian ultrasound should be performed to visualise the ovaries.
Management of PCOS is essentially symptomatic. Hirsutism and acne are managed by agents designed to inhibit hyperandrogenism, such as the combined oral contraceptive pill, anti- androgens (such as cyproterone acetate or spironolactone), and eflornithine hydrochloride,
Case 12: Excessive Hair Growth and Infertility 33
as well as laser or electrolysis for hair removal. The presence of chronic anovulation carries a higher risk of endometrial hyperplasia and carcinoma, and therefore requires treatment (typically with the contraceptive pill or cyclical progestogens). Ovulation may be induced with the use of clomiphene (an oestrogen receptor antagonist at the hypothalamus).
PCOS also carries a significant risk for the development of metabolic and cardiovascular dis
ease, including obesity, impaired glucose tolerance and diabetes and accelerated atheroscle
rosis. The likely pathophysiology behind these is insulin resistance, since women with PCOS are usually hyperinsulinaemic. These longer-term complications require similar manage
ment to type 2 diabetes, with weight reduction and certain antidiabetic agents (metformin and the thiazolidinediones) forming the mainstay of treatment.
KEY POINTS
• Hirsutism refers to the excessive growth of hair in a male pattern in women.
• It may arise from elevated androgen levels or be idiopathic.
• PCOS is a clinical diagnosis that often presents with hirsutism and oligomenorrhea or amenorrhoea.
• The mechanism of hyperandrogenism in PCOS is unclear but may relate to increased GnRH and LH pulsing.
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