Too Much Hair:
Hypertrichosis, Hirsutism and Androgenic Manifestations in Women
Dr. Nelson Soucasaux, Brazilian gynecologist
Hypertrichosis and hirsutism are the excessive growth of hair on the
female body, specifically a thick and usually dark type of hair. Though
the differences between hypertrichosis and hirsutism concern mostly the
degree and extension of the excessive hairiness, I would like to make some
important points regarding these concepts. The designation hypertrichosis
is more appropriate for the excessive growth of hair
on the parts of the female body in which all women normally have thick hair,
as the genitals and their surrounding and/or near areas. On
the other hand, the term hirsutism, besides
including all severe forms of hypertrichosis, concerns
mostly the significant growth of thick hair on those parts of women's
bodies in which the presence of hair is quite unusual and abnormal.
Frequently associated to acne, hypertrichosis and hirsutism are part
of the well-known androgenic manifestations in women. In cases of actual
hyperandrogenic disorders (that is, the presence of considerably high androgen
levels), these manifestations may also include, in their more severe forms,
other signs and symptoms like hypertrophy [enlargement] of the clitoris,
male-like changes in the voice, severe menstrual alterations including amenorrhea,
hair loss and several other problems (see Note
1 below).
Nevertheless, most of the cases of hypertrichosis and hirsutism that
we see in clinical practice - associated or not to disorders of the ovarian
cycle -, are slight or mild ones and only rarely are due to major disorders in
the androgenic metabolism. Usually they comprehend two basic groups with
several in-between situations : 1) slightly heightened androgen levels and/or
other slight alterations in the metabolism of these hormones; 2) increased
sensitivity and responsivity of the androgen-receptors to these hormones.
Before continuing, I have to call everybody's attention to the existence
of iatrogenic [caused by a doctor] cases of hypertrichosis and/or
hirsutism - and even menstrual disorders - due to the ill-advised use
of androgens and other steroids possessing androgenic properties, like some
medicines for "gaining weight" and "developing musculature"
("anabolizing" steroids). Women should never use such products,
and this must be quite clear.
Most cases of slightly or moderately heightened androgen levels are
usually due to ovarian pathologies like those of the polycystic ovaries
group and also a condition named hyperthecosis (also present in polycystic
ovaries). In these pathologies the ovaries not only produce an increased
amount of the androgens androstenedione and/or testosterone but also there
is a deficiency in their respective transformation into the estrogens estrone
and estradiol. As it is widely known, the androgens are the biochemical
precursors of the estrogens in the biosynthesis of the sexual hormones.
Androstenedione is turned into estrone both in the ovaries and the adipose
tissue. Testosterone is turned into estradiol in the ovaries.
Typical polycystic ovaries are characterized by: 1) interruption of
the follicular growth in its earlier stages, resulting in the presence of
a great number of small follicles that do not continue their development;
2) hyperplasia of the follicular theca and the ovarian stroma (hyperthecosis),
responsible mostly for the production of androgens; 3) bilateral ovarian
enlargement; 4) thickening of the tunica albuginea, the ovarian external
coating; 5) chronic anovulation; 6) deficient conversion of androgens into
estrogens, with the consequent androgenic accumulation in the follicles;
7) excessive ovarian production of androgens; 8) the resulting increased
blood levels of androgens; 9) menstrual disorders like oligomenorrhea (long-lasting
cycles) and amenorrhea. For more details on this subject, see my articles
"Polycystic Ovaries Syndrome" and "The Curious Relation Between Androgens and Estrogens
in Women," published here at the MUM.
Some cases of moderately heightened androgen levels may also be due
to very slight forms of virilizing adrenal hyperplasias that may
become manifest only later in life (during adolescence and adulthood). Nevertheless,
we must emphasize that, in this pathology, the androgenic levels are usually
higher - even in its slightest forms. Virilizing adrenal hyperplasias are
genetically inherited pathologies of the adrenal glands mostly due to variable
degrees of 21-hydroxylase deficiency (21-hydroxylase is an enzyme whose
activity is fundamental in the synthesis of cortisol, one of the most important
hormones produced by the adrenal cortex. Cortisol plays a crucial role in
human endocrine physiology) (See Notes 2 and
3 below). If the adrenal glands fail in producing
the necessary levels of cortisol due to 21-hydroxylase deficiency, the pituitary
greatly increases its production of ACTH (adrenocorticotropic hormone) in
order to better stimulate the adrenal glands and try to improve the cortisol
levels. Nevertheless, this adrenal over-stimulation by continuous high levels
of ACTH ends up by generating the adrenal hyperplasia and the
consequent heightened production of androgens.
As already mentioned, another factor of great importance in many cases
of hypertrichosis and hirsutism concerns the peripheral androgenic metabolism
and the responsiveness of the androgen-receptors to these hormones. In clinical
practice we frequently verify that many cases of slight hypertrichosis and/or
hirsutism do not exhibit any significant alteration in the ovarian and/or
adrenal production of androgens. These cases are considered constitutional,
since the main origin of the problem seems to be an increased responsiveness
of the hair follicles to normal levels of androgens.
The androgen that really stimulates most of the androgen-receptors is
not testosterone, but dihydrotestosterone. Dihydrotestosterone results
exclusively from the peripheral conversion of androstenedione and testosterone
and depends on the activity of an enzyme named 5-alpha-reductase. Under
the action of 5-alpha-reductase, androstenedione and testosterone are turned
into dihydrotestosterone at the level of the tissues sensitive to the androgens
(see Note 4 below). In this way, the origin
of many cases of slight hypertrichosis and hirsutism may be an increased
activity of this enzyme, resulting on a higher rate of conversion of androstenedione
and testosterone into dihydrotestosterone and a consequent major stimulation
of the hair-follicles' androgen-receptors. As dihydrotestosterone is an
exclusive result of peripheral transformation, it is not produced
by the ovaries and adrenals, and this must be quite clear.
In the genesis of several cases of androgenic manifestations in women,
several authors also attribute considerable importance to the rate of testosterone's
liaison to the SHBG (sexual hormone binding globulin), a plasmatic protein
that carries the sexual hormones in the bloodstream. In this way, the amount
of testosterone linked to the SHBG would not be promptly available in terms
of biological action, while the not-linked testosterone (free-testosterone)
is immediately ready for biological use. It is said that the estrogens,
by stimulating the production of SHBG, indirectly increase the liaison of
testosterone to this globulin, reducing the amount of free-testosterone.
All cases of hypertrichosis, hirsutism and other androgenic manifestations
in women require careful investigation of the ovarian and adrenal function.
Nevertheless, most of the cases of slight hypertrichosis and/or hirsutism
are mostly due to ovarian dysfunctions and/or constitutional factors.
In cases like these, the adrenal dysfunctions do not seem to be so
frequent (or are much harder to detect). Among the ovarian dysfunctions,
the most frequent ones are, as already said, those related to the polycystic
ovaries and hyperthecosis. The most frequent adrenal dysfunction is the
21-hydroxylase deficiency. In some cases, ovarian and adrenal dysfunctions
may be associated. It is also important to emphasize that we only consider
a case as constitutional when the result of all hormonal investigations
is normal.
Before finishing, given the complexity of the subject, I would like
to make it clear that this is only a very, very introductory article on
hypertrichosis, hirsutism and other androgenic manifestations in women.
A detailed approach to this subject would obviously require a series
of articles. I also would like to remark that I did not mention the several
existing treatments for the problem in order to avoid self-medication
on the part of some readers.
Note 1: Though
they are not the subject of this article, some words must be said about
the serious hyperandrogenic disorders. These ones are usually
due to severe virilizing adrenal hyperplasias and ovarian and adrenal
tumors that produce androgens. A remarkable point here is that the clinical
manifestations of these conditions vary according to the phase of life in
which they become manifest. If the excessively heightened androgen levels
appear during intrauterine life, mostly in the period of sexual differentiation,
female fetuses will suffer total or partial masculinization of the external
genitals. If they appear in childhood, the result in the female sex will
be heterosexual precocious pseudo-puberty (appearance of some male puberty
signs in little girls). If the very heightened androgen levels appear later
in life, women will present severe hirsutism, clitoral hypertrophy, serious
menstrual disorders including amenorrhea, male-like changes in the voice,
hair loss, etc.
Note 2: The
adrenal glands comprehend two regions, the cortical and the medular ones.
The cortical region, known as adrenal cortex, produces basically three groups
of hormones: 1) the glucocorticoids, of which cortisol is the most important
one; 2) the mineralocorticoids, of which aldosterone is the main one; 3)
sexual steroids, mostly androgens. The adrenals are an important source
of androgens, both in women and men, and this is what matters the most for
our subject. The function of the adrenal cortex is mostly controlled by
the pituitary through the production of ACTH (adrenocorticotropic hormone).
As for the adrenal medular region, it produces adrenalin under nervous stimulation.
Note 3: 11-beta-hydroxylase
is another adrenal enzyme whose activity is fundamental for the synthesis
of aldosterone. By regulating the balance of sodium in the organism, aldosterone
is another very important adrenal hormone. There are also cases of virilizing
adrenal hyperplasias due to a deficiency of 11-beta-hydroxylase, but they
are very rare.
Note 4: In
men, a congenital deficiency of 5-alpha-reductase causes the androgen
insensitivity syndrome, formerly known as testicular feminization.
Copyright Nelson Soucasaux 2006
__________________________________________
Nelson Soucasaux is a gynecologist dedicated to clinical,
preventive and psychosomatic gynecology. Graduated in 1974 by Faculdade
de Medicina da Universidade Federal do Rio de Janeiro, Brazil, he is the
author of several articles published in medical journals and of the books
"Novas Perspectivas em Ginecologia" ("New Perspectives
in Gynecology") and "Os Órgãos Sexuais Femininos:
Forma, Função, Símbolo e Arquétipo" ("The
Female Sexual Organs: Shape, Function, Symbol and Archetype"), published
by Imago Editora, Rio de Janeiro, 1990, 1993. He has been working in
his private clinic since 1975.
Web site (Portuguese-English): www.nelsonginecologia.med.br
Email: nelsons@nelsonginecologia.med.br