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Int J Trichology
v.2(1); Jan-Jun 2010
PMC3002408
Endocrinology of Hirsutism
Daisy Kopera, Elisabeth Wehr,1 and Barbara Obermayer-Pietsch1
Abstract
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INTRODUCTION
Hirsutism may result from various endocrine disorders [Table 1]. Polycystic
ovary syndrome (PCOS) is the most common endocrine disorder in
premenopausal women (incidence 5 10%).[13] It was recognized by the
Italian physician Antonio Vallisnerie, in 1721, who reported cystic ovaries in
overweight infertile women. In 1921, French physicians Achard and Thiers
found some coincidence between diabetes and hyperandrogenism when they
coined the term femmes barbe diabetique (=diabetic women with
beard).[4] The first systematic description mentioning amenorrhea, hirsutism,
obesity, and polycystic ovaries was published by Irving Stein and Michael
Leventhal, American gynecologists, in 1935. The so-called Stein-Leventhal-
syndrome is a condition heavily influencing a womans reproductive abilities,
as well as metabolic and cardiovascular health.[5]
Table 1
Causes of hirsutism
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DIAGNOSIS OF PCOS
Diagnosing PCOS is not easy as signs and symptoms are heterogenous and
vary from time to time. Diagnostic criteria have been summarized by the
European Society for Human Reproduction (ESHRE) and the American
Society for Reproductive Medicine (ASRM), in 2003, and denominated as
Rotterdam Criteria. The presence of any two of the following three
conditions corroborates the diagnosis of PCOS: oligo/anovulation,
hyperandrogenism or polycystic ovaries.[Figure 1, Table 2]. All other
causative diseases such as hyperprolactinemia, late onset-AGS
(adrenogenital syndrome), genetic deficiency of 21-hydroxylase, Cushings
syndrome, androgen-producing neoplasms, acromegaly, primary
hypothyroidism, premature ovarian failure, and drug-associated hirsutism or
dysmenorrhea have to be excluded.[5,6] Thus, we are faced with the fact that
PCOS is a functional state. Polycystic ovaries per se, do not necessarily have
to be present for the diagnosis of PCOS; on the other hand, polycystic ovaries
alone do not justify the diagnosis of PCOS. The newest diagnostic guideline
was made by the Androgen Excess and PCOS Society, in 2006; they claim
the presence of hyperandrogenism and ovarian dysfunction
(oligo/anovulation and/or polycystic ovaries).[7]
Figure 1
Sonographic appearance of polycystic ovaries
Table 2
Phenotypes of PCOS based on various symptoms and definitions (NIH,
Rotterdam und AE-PCOSCriteria).[7]
Besides anovulation, limited fertility, sparse or lacking menstrual bleeding,
and hyperandrogenism, PCOS may also feature dermatological conditions
such as hirsutism, acne, and androgenetic alopecia, whereas, acanthosis
nigricans is more common in hyperinsulinism. More than 50% of PCOS
patients are obese. Obesity-associated reproductive and metabolic
dysfunctions may aggravate the symptoms of PCOS. On the other hand, lean
PCOS phenotypes might be underestimated for the syndrome.
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GONADOTROPHINS
The pathogenesis of PCOS is multifactorial and depends on the biosynthesis
of the steroid hormones. Triggered by the luteinizing hormone (LH) from the
pituitary gland, ovarian theca cells produce androgens [Figure 2]: cytochrome
P-450c17 (an enzyme with 17-hydroxylase- and 17,20-lyase-activity)
induces the production of androstendione. This is then metabolized into
testosterone by 17-hydroxysteroid dehydrogenase or into estron by
aromatase. In PCOS patients, this metabolic step is in favor of testosterone
production.
Figure 2
Pathogenesis of PCOS[5]
The Follicle-stimulating hormone (FSH) from the pituitary gland regulates
aromatase-activity in granulosa cells and thereby the production of estrogens.
Increased Luteinizing Hormone (LH) levels, compared to the FSH, result in
increased androgen production in the ovaries.
The Gonadotropin-releasing hormone (GnRH) dominates LH/FSH secretion
in the pituitary. High GnRH expression increases LH and low GnRH
increases FSH synthesis. In PCOS patients the increased LH/FSH ratio
relates to a high GnRH excretion, but it is still uncertain if an intrinsic
malfunction of the GnRH pulse generator or relatively low levels of
progesterone, as a result of anovulatory menstrual cycles, are the underlying
cause [Figure 2].[5] High GnRH expression could also be caused by low
pituitary progesterone sensitivity, due to low circulating androgens. This is
supported by the fact that progesterone sensitivity can be increased by the
therapeutic use of flutamide, an androgen receptor antagonist.[4]
In females the free androgen index (FAI) [FAI = 100 (FT/SHBG)], as a
marker of PCOS, may be misleading in obese patients because obesity
reduces sex hormone-binding globulin (SHBG) levels. Elevated FAI values
may correlate more with obesity and less with PCOS.[8] The best
biochemical marker for polycystic ovary syndrome is a raised testosterone
level. Therefore, the FAI does not necessarily aid the biochemical diagnosis
of PCOS.[9]
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Figure 3
Modified Ferriman-Gallwey-score[13]
Table 3
Terminal hair (in %) in several body areas in hirsute women
Hyperandrogenism, insulin-resistance, and adrenogenital syndrome represent
a sub-type of PCOS that is often based on genetic predisposition. There seem
to appear two types: type A which is hereditary and showing insulin
resistance due to insulin receptor mutation, type B may be based on auto-
immunological reasons. Both types develop antibodies against insulin
receptors. Accompanying reproductive disorders appear as abnormal
menstrual cycles, infertility and spontaneous abortion.[14]
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HYPERTHECOSIS
Hyperthecosis represents a benign condition of the ovary characterized by
increased testosterone production triggered by luteinized Theca-cells.
Whether this correlates with PCOS, needs to be clarified.
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DRUG-DEPENDENT HIRSUTISM
Testosterone, Dehydroepiandrosterone (DHEA), progesterone (e.g.,
danazole), corticosteroids, Adrenocorticotropic hormone (ACTH), and also
non steroidal drugs (diphenylhydantoine, diazoxide, etc.) may be causes for
hirsutism.[16]
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LHRH-TESTING
The pituary gland plays a key role in the pathogenesis of PCOS. Therefore
LHRH-testing with 25g busereline i.v. may be helpful. Sixty minutes after
application of busereline, the LH/FSH ratio should be measured, in order to
detect hyperstimulation.
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CONCLUSION
In summary, PCOS is a highly frequent and often underestimated disorder in
a considerable segment of hirsute women. The complex metabolic and
hormonal disturbances require a concomitant interdisciplinary and
individualized therapy.
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Footnotes
Source of Support: Nil
Conflict of Interest: None declared.
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