hirsutism, the role of androgens, virilization, hypertrichosis, treatment, and management of hirsutism

1. HIRSUTISM -RAVALI (1ST year PG)

2. DEFINITION
Hirsutism, defined as excessive growth of terminal hair in male disturbution
pattern -facial and body hair, affects between 5 and 10% of reproductive age
women.
This refers particularly to midline hair, side burns, moustache, beard, chest or
intermammary hair, and inner thigh and midline lower back hair entering the
intergluteal area.
The response of the pilosebaceous unit to androgens in these androgen
responsive areas transforms vellus hair (fine, nonpigmented, short) that is
normally present into terminal hair (coarse, stiff, pigmented, and long).

4. Three types of Hair :
 Lanugo : Body hair seen in the fetus and
newborn
Vellus : Fine adult hair covering the body
 Terminal hair : Thick pigmented hair of scalp
and pubic area
Thickness of the terminal hair varies form one
individual to other depending upon genetic, and
possibly nutritional factors

5. OTHER CONDITIONS ASSOCIATED WITH EXCESS
HAIR-
HIRSUTISM
HYPERTRICHOSIS
VIRILIZATION

6. HYPERTRICHOSIS
Hypertrichosis is the term reserved for androgen-independent terminal hair in
non-sexual areas, such as the trunk and extremities.
This may be the result of an
-autosomal-dominant congenital disorder,
-a metabolic disorder (as anorexia nervosa, hyperthyroidism, porphyria
cutanea tarda),
-heavy metals,
-interferon,
-methyldopa,
-medications (e.g., acetazolamide, anabolic steroids, androgenic
progestins, androgens, cyclosporine, diazoxide, dehydroepiandrosterone (DHEA),
minoxidil, penicillamine, phenothiazines, phenytoin, streptomycin, reserpine,
valproic acid

8. VIRILIZATION
Excess sex hair growth and other hyper androgenic effects on female
genitalia and body.
 Virilization describes the signs and symptoms of more severe androgen
excess,
-deepening of the voice,
-temporal balding (androgenic alopecia),
-features of defeminization (loss of breast volume and
body fat contributing to feminine body contour)
-changes in body habitus, and
-clitoromegaly.
Virilization is rare and most commonly results from congenital

10.  Although hirsutism accompanies virilization, the presence of virilization
indicates a high likelihood of more serious conditions than are common
with hirsutism alone and should prompt evaluation to exclude ovarian or
adrenal neoplasm.
The history should focus on the age of onset and rate of progression of
hirsutism or virilization.
Anovulation, manifesting as amenorrhea or oligomenorrhea, increases the
probability that there is underlying hyperandrogenism.
When virilization is present, anovulation virtually always occurs.
Hyperandrogenism most often presents as hirsutism, which usually arises
as a result of androgen excess related to abnormalities of function in the
ovary or adrenal glands, the constative increase in expression of androgen
effects at level of pilosebaceous unit or both.
Hirsutism occurring with regular cycles is more commonly associated with
normal androgen levels and thus is attributed to increased genetic
sensitivity of the pilosebaceous unit and is termed idiopathic hirsutism.

11. EFFECT OF ANDROGENS ON HAIR – IN
RELATION TO SPECIFIC REGIONS
Hair that shows no androgen dependence includes lanugo, eyebrows, and
eyelashes.
The hair of the limbs and portions of the trunk exhibits minimal sensitivity to
androgens.
Pilosebaceous units of the axilla and pubic region are sensitive to low levels
of androgens, such that the modest androgenic effects of adult levels of
androgens of adrenal origin are sufficient for substantial expression of
terminal hair in these areas.
Follicles in the distribution associated with male patterns of facial and body
hair (midline, facial, inframammary) require higher levels of androgens, as
seen with normal testicular function or abnormal ovarian or adrenal androgen
production.
Scalp hair is inhibited by gonadal androgens, in varying degrees, as

12. ROLE OF ANDROGENS
Androgens and their precursors are produced by both the adrenal glands and
the ovaries in response to their respective trophic hormones,
adrenocorticotropic hormone (ACTH) and luteinizing hormone (LH).
Hirsutism reflects the interaction between circulating androgen levels and the
sensitivity of hair follicles to androgen stimulation.
In women, the major circulating androgens (in descending order of serum
concentration) are
dehydroepiandrosterone sulfate (DHEA-S)
dehydroepiandrosterone (DHEA),
androstenedione,
testosterone,
DHT.
DHEA-S, DHEA, and androstenedione can be considered pre-hormones
because they have little or no intrinsic androgenic activity and require

14. ANDROGEN PRODUCTION
DHEA-S is produced almost exclusively by the adrenal glands.
DHEA is produced by both the adrenals (50%) and the ovaries (20%),
and from the peripheral conversion of DHEA-S (30%).
Androstenedione production is divided equally between the ovaries
and the adrenals.
Testosterone production derives from the adrenals (25%), the ovaries
(25%), and from peripheral conversion of androstenedione (50%). ,
DHT

15. DHEA-S
50%

19. DHEA-S is produced almost exclusively by the adrenal glands, at a rate
ranging between 3.5 and 20 mg/day
the normal serum concentration is 100–350 mg/dL in most
laboratories.
The production rate of DHEA is between 6 and 8 mg/day
normal serum concentrations range between 1 and 10 ng/mL
Androstenedione production is divided equally between the ovaries and
the adrenals; the production rate is between 1.4 and 6.2 mg/day
the normal serum concentration is 0.5–2.0 ng/mL.
Serum immunoassays for DHEA-S, DHEA, and androstenedione
generally reflect the amount of biologically available hormone because
none of the three is protein-bound to any significant extent.

20. DHT-DIHYDROTESTOSTERONE
Although testosterone is the major circulating androgen, DHT is the major
nuclear androgen in many androgen-sensitive tissues, including hair follicles and
sebaceous glands.
DHT is produced only in the periphery, by intracellular conversion of testosterone
(via 5a-reductase).
Circulating levels of DHT are, therefore, very low and do not reflect the level of
5a-reductase activity.
3a-androstanediol is the peripheral tissue metabolite of DHT, and its glucuronide
conjugate, 3a-androstanediol glucuronide (3a-AG), can be used as a marker of
peripheral androgen metabolism.
Serum 3a-AG levels correlate highly with levels of 5a-reductase activity in genital
skin and are elevated almost uniformly in hirsute women, including those with
normal serum androgen levels, indicating that “idiopathic” hirsutism likely results
from increased peripheral 5a-reductase activity.

21. TESTOSTERONE
The production rate ranges between 0.1and 0.4 mg/day and the normal serum
concentration is 20–80 ng/dL;
Testosterone is bound to serum hormone-binding globulin (SHBG).
Similarly, obesity causes fall in SHBG as well as more peripheral conversion of
androstenedione to Testosterone.
However, the androgenic actions of testosterone relate primarily to the amount
of free hormone and, to a limited extent, to the fraction associated with
albumin.
Anything that affects the SHBG concentration also affects the concentration of
free/active testosterone.

22. Role: Bind to and carry testosterone (and less
strongly E2 and DHT) through the blood
stream to target tissues and to the liver for
modification and removal from the body. This
bond is very strong. The bound testosterone
is not easily removed from the SHBG and is
therefore considered inactive.
Production Sites: Liver mostly, testes, brain
Production Signals: Estradiol, triiodothyronine
(T3)
Down-Regulated by: Insulin
Action: Controls clearance and bioavailability
of testosterone
SHBG production in the liver is inhibited by androgens and is increased by
estrogen and thyroid hormone.
Low estrogen and thyroid hormone cause fall in SHBG level, and this
results in some testosterone being released into the blood circulation as
free T, which can cause hirsutism.

23. Although specific assays to measure the level
of free testosterone are available, they are
costly and rarely necessary. The very
presence of hirsutism or virilization indicates
androgen excess.
In hirsute women with “normal” serum total
testosterone levels, decreased binding
capacity and increased free testosterone can
be assumed.
Hirsutism results from both increased
androgen production and skin sensitivity to
androgens.
Skin sensitivity depends on the genetically
determined local activity of 5α-reductase,
the enzyme that converts testosterone to
dihydrotestosterone (DHT), the bioactive
androgen in hair follicle.

24. ETIOLOGY -
-PCOS
-Hyperandrogenic insulin-resistant acanthosis nigricans (HAIR-AN) syndrome
-Idiopathic hirsutism
-Congenital adrenal hyperplasia
-Androgen-secreting neoplasms of the ovary or adrenal
-hyperprolactinemia
-pregnancy luteoma
-theca-lutein cysts(hyperreactio luteinali)

25. EVALUATION OF WOMEN WITH
HIRSUTISM
Accepting that the large majority of women with hirsutism have PCOS
or idiopathic hirsutism, the evaluation of hirsute women is aimed at
identifying the few having other causes that require additional
specific evaluation and/or treatment.
As always, evaluation should begin with a
-careful history and
-physical examination, which always provide important diagnostic
clues.
-Laboratory investigation & Imaging (exclude other rare or
serious possibilities)

26. 1. HISTORY
2. PHYSICAL EXAMINATION
3. LAB- INVESTIGATIONS & IMAGING

27. 1. HISTORY-
the menstrual history
•age at menarche,
•the regularity of menses,
•a characterization of
premenstrual molimina,
•any previous pregnancies
and
•methods of contraception
age at onset
•childhood usually is caused
by classical CAH or an
androgen-secreting tumor.
•Rare genetic causes -such
as Y-chromosome
mosaicism or incomplete
androgen insensitivity,
usually present with signs
of androgen excess at
puberty.
•Pcos also around puberty
•A later age at onset of
hirsutism (after age 25) or
rapid progression over a
period of months suggests
an androgen producing
neoplasm.
•Elderly women at
menopause
-the family H/0
•of oligo/amenorrhea,
obesity, and infertility are
consistent with a familial
predisposition to PCOS or,
occasionally, nonclassical
CAH, which is more
-medication history
•that can stimulate hair
growth include
methyltestosterone,
anabolic steroids (e.g.,
norethandrolone),
phenytoin, diozoxide,
danazol, cyclosporin, and
minoxidil.
•DHEA or androstenedione,
-available as food
supplements, can increase
testosterone levels in
women and cause hirsutism
and acne, even at relatively
low doses.
•The hair growth caused by
medications, other than
androgens, typically is
diffuse and vellus in nature
(hypertrichosis).
The key elements of the medical history in women with hirsutism
include-

28. -. It is important to correlate changes in menstrual pattern with changes in
weight and to remember that previous hormonal contraception could have
obscured or delayed the onset of symptoms of menstrual dysfunction or
androgen excess.
Whereas women with PCOS typically report menstrual irregularity beginning at or
soon after menarche, an abrupt departure from a previously established pattern
of regular menses suggests another diagnosis.
- the rate of progression of hirsutism is also an important criteria

29. PHYSICAL EXAMINATION-
The physical examination should include a calculation of the body
mass index (BMI) and document the distribution and extent of
hirsutism.
The modified Ferriman-Gallwey score is the most common method
for grading the extent of hirsutism in clinical investigations.
Approximately 95% of women have a modified Ferriman-Gallwey
score less than 8.
Approximately 22% of women have scores of 3 or higher, 70% of
which complain of hirsutism.
Notably, approximately 15% of women with scores less than 3 also
consider themselves hirsute.

30. MODIFIED
FERRIMAN-
GALLWEY SCORING
SYSTEM FOR
HIRSUTISM
The method derives from studies in white
women and scores hair growth from 0–4 in
each of 9 androgen-sensitive areas, including
the upper lip, chin, chest, upper and lower
abdomen, upper arm, thighs, and the upper
and lower back.
Scores less than 8, 8–15, and greater than 15
generally indicate mild, moderate, and severe
hirsutism, respectively.

31. THE SCALE AND ITS
DISADVANTAGES-
It is quite normal for most women to have at least some hair growth in
androgen-sensitive areas and that a score of 8 or higher reflects significant
androgen excess that warrants evaluation.
It is difficult to use clinically, primarily because most women who seek
medical attention for the complaint already are using one or more methods of
hair removal.
Score is unreliable for women in racial or ethnic groups having relatively little
body hair; although less likely to develop hirsutism, they can exhibit other
signs of androgen excess, such as acne and thinning or loss of hair.
The easiest and most practical way to assess the severity of hirsutism is to
determine the methods used to remove hair (e.g., shaving, plucking, waxing)
and the frequency of their use, which also provides a clinically relevant
measure for assessing the response to treatment.

32. The physical examination also should note other relevant
skin manifestations and any signs of virilization.
-Acne, seborrhea, and temporal balding are signs of androgen excess.
-Acanthosis nigricans (a gray or brown velvety discoloration of the skin,
most commonly observed at the nape of the neck, the groin and axillae)
indicates insulin resistance
-Thin skin, striae, or bruising are signs of hypercortisolism.
-signs of virilization include deepening of the voice, increased muscle
mass, breast atrophy, and clitoromegaly.
(Clitoromegaly generally is defined by a clitoral length greater than 10 mm
or by a clitoral index (length times width) greater than 35 mm2,)
- Other relevant physical findings include spontaneous or expressible
galactorrhea, suggesting hyperprolactinemia
-abdominal or pelvic masses that may represent an androgen-secreting
tumor. The large majority of functional ovarian tumors are palpable

33. - Alopecia In many cases, alopecia is only temporary, resulting from
telogen effluvium induced by some transient change that
synchronizes a larger than normal proportion of scalp hair follicles,
such as pregnancy or a febrile illness, and resolves after a period of
6–8 months
The physical manifestations of androgen excess generally reflect the
extent to which androgen levels are elevated. Hirsutism is the most
common complaint associated with androgen excess and essentially
all women with hirsutism have an increased production rate of
testosterone and androstendione.
Acne, increased libido, clitoromegaly, and virilization reflect
progressively higher serum androgen levels.

35. KEY POINTS & RECOMMENDATIONS FOR -
LAB EVALUATION OF HIRSUTISM
1. Laboratory evaluation is recommended for women with moderate or
severe hirsutism, or hirsutism that is sudden in onset, rapidly
progressive, or associated with symptoms or signs of virilization.
Routine laboratory evaluation of women with mild hirsutism is
unnecessary.
 2. The serum total testosterone concentration is the best overall
measure of androgen production and is the only hormone that need be
measured in most women with hirsutism that merit evaluation.
3. An androgen-secreting tumor should be suspected, and excluded, in
women with rapidly progressive hirsutism, symptoms or signs of
virilization, or a serum testosterone concentration 150 ng/dL or greater.
However, most such patients will not have a tumor.

36. 4. Nonclassical congenital adrenal hyperplasia should be suspected, and
excluded, in patients with an early onset of hirsutism (pre- or peri-
menarcheal, including those with a premature adrenarche), women with a
family history of the disorder, and those in high-risk ethnic groups
(Hispanic, Mediterranean, Slavic, and Ashkenazi Jewish heritage).
 5. Cushing syndrome should be suspected, and excluded, in women with
symptoms and signs of hypercortisolism.
Laboratory evaluation is indicated for many but not all women with
hirsutism.
The primary aim is to identify those having potentially serious endocrine
disorders requiring specific treatment (nonclassical CAH, androgen-
secreting tumors, Cushing syndrome).
Thyroid disorders and hyperprolactinemia should be excluded in women
with menstrual dysfunction.

37. Routine laboratory evaluation of women with mild hirsutism is neither
necessary nor cost-effective.
In women with oligo/amenorrhea, mild hirsutism can be attributed
confidently to increased ovarian androgen production resulting from
chronic anovulation.
In women with regular menses, hirsutism most likely reflects an
increased sensitivity to androgens relating to increased peripheral 5a–
reductase activity.

38. IMAGING
Ultrasound Scan It is useful to detect an ovarian tumour, PCOD
and adrenal tumour.
CT scan and MRI are needed in case pituitary or adrenal tumour
is suspected. Laparoscopic visualization of pelvic organs,
dexamethasone and ACTH tests are necessary.

39. MANAGEMENT
1. Treat the cause -Removal of ovarian and adrenal tumour will stop further
hirsutismPCOD will require to be treated with ovulation
induction/laparoscopic laser or cautery for puncture of cysts.
2. Drugs.
3.Weight reduction -will elevate SHBG and bind free testosterone, thus
reducing its peripheral action on hair follicles.
4. Cosmetics. Bleaching, waxing, shaving, and laser are useful in removal of
facial hair. Electrolysis is highly satisfactory in treating hirsutism

40. The treatment of hirsutism should be directed towards its cause,
whenever possible, but also must consider the extent to which the
patient views it as a problem, and her therapeutic and reproductive
goals.
Whereas laboratory evaluation is recommended only for women with
moderate or severe hirsutism, treatment should be considered for all
women who judge themselves hirsute; many with mild hirsutism are
worried or bothered by their hair growth and seek treatment.
The severity of hirsutism should be defined before treatment begins to
provide the means for monitoring response; the methods and frequency
of hair removal provide the most practical and clinically relevant
measure.
Serial measurements of serum androgen levels during treatment are
neither necessary nor helpful, but repeated evaluation is indicated when
hirsutism progresses despite treatment

41. Before treatment begins, it also is important to foster reasonable
expectations regarding its likely impact. Finer, lighter and slower hair
growth, and the prevention of new terminal hair growth, all can be
expected; a complete cessation or elimination of hair growth cannot.
No significant reduction in hair growth may occur for up to 6 months,
which approximates the half-life of a hair follicle growth cycle. After 6
months, a change in dose, drug, or the addition of a second drug should
be considered if the patient judges her response inadequate.
In general, treatment should be continued indefinitely because the
problem rarely goes away and almost always recurs when treatment is
discontinued.
Patients planning to attempt pregnancy are the obvious exception,
because most treatments prevent pregnancy or are contraindicated
during pregnancy due to the risk of adverse impact on sexual

42. Treatments for hirsutism are aimed at
-reducing the production,
- increasing the binding, and/or blocking the action of androgens, and
-estrogen-progestin contraceptives
-antiandrogens are the primary weapons in the therapeutic arsenal.
It is important to emphasize that even women with idiopathic hirsutism
relating to increased end organ sensitivity to androgens can benefit
from treatments that lower free/active androgen concentrations or
block the androgen receptor; clinical response correlates with
circulating levels of 3a-androstanediol glucuronide (the peripheral
metabolite of dihydrotestosterone), supporting increased peripheral 5a-
reductase activity as the cause of idiopathic hirsutism

43. TREATMENT
ESTROGEN –
PROGESTIN
CONTRACEPTIV
ES
ANTI-
ANDROGENS
INSULIN
SENSITIVE
AGENTS
OTHER
TREATMENT
PERMANENT
HAIR REMOVAL
SPIRNOLACTONE
Cyproterone acetate
FLUTAMIDE
GLUCOCORTICOI
DS
ELECTRO
LYSIS
LASER
GNRH
RELEASING
HARMONE
AGONIST
FINASTRIDE
Eflornithine
Hydrochloride

44. ESTROGEN-PROGESTIN
CONTRACEPTIVES
Estrogen-progestin contraceptives have a number of complementary non-
contraceptive actions that make them a logical and effective treatment for
hirsutism:
● Androgen production in hirsute women usually is an LH-dependent
process. Estrogen- progestin contraceptives suppress pituitary LH
secretion and thus also suppress ovarian androgen production.
● The high level of estrogen in combination contraceptives stimulates
hepatic SHBG production, thereby increasing binding capacity for
circulating androgens and decreasing the amount of free/active androgen.
● Directly or indirectly, estrogen-progestin contraceptives can decrease
adrenal DHEA-S secretion.
● Contraceptive progestins inhibit 5a-reductase activity in skin, which
decreases the production of dihydrotestosterone (DHT), the major nuclear
androgen in hair follicles and sebaceous glands.

45. Most hirsutism results from chronic anovulation, which frequently
causes menstrual irregularity and episodic dysfunctional bleeding,
and also predisposes to abnormal patterns of endometrial growth.
Treatment with estrogen-progestin contraceptives induces regular,
predictable menses and attenuates endometrial growth, thereby
eliminating the risk for developing endometrial hyperplasia and
neoplasia
Current oral contraceptives contain
ethinyl estradiol, in doses ranging from 20 mg to 50 mg
daily,
& one of a variety of progestins.
All low-dose oral contraceptives (containing 20–35 μg ethinyl
estradiol) have similar effectiveness in the treatment of acne and
hirsutism.

46. Although estrogen induces a dose-dependent increase in serum SHBG
concentrations, low- and higher-dose pills suppress free testosterone
levels to a comparable extent.
The transdermal contraceptive patch (delivering 20 mg ethinyl estradiol
and 150 mg norelgestromin daily) and the vaginal contraceptive ring
(releasing 15 mg ethinyl estradiol and 120 mg etonogestrel daily) also can
be used for the treatment of hirsutism,
For patients with contraindications to the use of
estrogen-progestin contraceptives, treatment with
medroxyprogesterone acetate (150 mg intramuscularly
every 3 months, or 10–20 mg orally daily) is an alternative.

47. Clinical improvement reflects the decrease in free/ active androgen during
treatment: new terminal hair growth decreases or stops, termina hairs already
present grow more slowly and produce finer hair, and acne gradually improves
or disappears.
Hormone therapy must be continued for at least 6 months before judging its
effectiveness.
In the meantime, the patient can continue to use her preferred method of hair
removal (e.g., shaving, plucking, waxing).
After 1–2 years, or when pregnancy becomes the goal, treatment can be
discontinued and the patient observed for a return of ovulatory cycles,
although most again will exhibit chronic anovulation.
Permanent hair removal by electrolysis or laser methods may be required
ultimately, at least in some patients, but is best postponed until hormonal
suppression has achieved its maximum benefits.
Treatment with low-dose oral contraceptives does not adversely affect lipid
and biochemical markers for cardiovascular disease, retinopathy, or
nephropathy in women with insulin-dependent diabetes and has very limited
impact on glucose tolerance, even in obese women with severe insulin

48. ANTI ANDROGENS
ANTI
ANDROGENS
CYPROTERONE
ACETATE
FLUTAMIDE FINASTRIDE SPIRNOLACTONE
 Antiandrogens are an effective treatment for hirsutism, but are best used with
contraception, because they have the potential to adversely affect sexual development
in a male fetus if the patient conceives during treatment.
 In patients with contraindications to oral contraceptives, an alternative means of reliable
contraception (e.g., an intrauterine device) should be provided during treatment with
antiandrogens. Combined treatment with oral contraceptives and antiandrogens also is
a logical choice for patients who respond inadequately to oral contraceptives alone.

49. SPIRONOLACTONE
Spironolactone is an aldosterone antagonist having structural similarity to
progestins.
The drug also acts as an androgen receptor antagonist, competing with
dihydrotestosterone (DHT) for binding to the androgen receptor, and to
varying extent, also inhibits ovarian and adrenal androgen synthesis.
Although serum androstenedione levels decrease, those of DHEA, DHEA-S
and cortisol do not significantly change during treatment with spironolactone.
The effects of spironolactone are dose-dependent and best results are
achieved with doses of 50–100 mg twice daily.
As with all treatments for hirsutism, maximal effects are observed only after
approximately 6 months of therapy.

50. Side effects are relatively few, including diuresis in the early days of
treatment and occasional complaints of fatigue and dysfunctional
uterine bleeding. Although the drug can cause hyperkalemia, the effect
is rare and monitoring of potassium levels is not necessary in women
with normal renal function.
The action of spironolactone, peripheral androgen receptor blockade,
nicely complements those of oral contraceptives and may thus provide
additional benefit for those who fail to achieve adequate results from
oral contraceptives alone.

51. CYPROTONE ACETATE
Cyproterone is a derivative of 17a-hydroxyprogesterone (17OHP) having potent
progestational activity that inhibits gonadotropin secretion.
competitive androgen receptor antagonist and inhibits enzymes involved in
androgen synthesis, like spironolactone.
Cyproterone acetate is the progestin in the combined estrogen-progestin oral
contraceptive called “Diane” (2 mg cyproterone acetate and 50 mg ethinyl
estradiol)
The drug also has been used in higher doses (12.5–100 mg), alone or in
combination with estrogen.
The most common side effects –
fatigue
edema
loss of libido
weight gain
mastalgia.

52. FINASTRIDE
Finasteride inhibits 5a–reductase and thus blocks the conversion of
testosterone into DHT.
The enzyme exists in two forms, with type 1 most prevalent in skin
and type 2 predominating in reproductive tissues.
Because external male genital development requires the action of
DHT, the risks of inadvertent finasteride treatment during pregnancy
are a particular concern
finasteride should not be used without a highly effective method of
contraception.

53. FLUTAMIDE
Flutamide is a nonsteroidal androgen receptor antagonist used
primarily in the treatment of prostate cancer.
The drug (250–750 mg daily) inhibits hair growth directly and is as
effective as spironolactone
its higher cost and potential for causing severe hepatotoxicity make it
an unattractive therapeutic choice, by comparison.

54. INSULIN-SENSITIZING DRUGS
-Insulin-Sensitizing Drugs Given that PCOS is the most common cause
of hirsutism and that insulin resistance is a common feature of the
disorder, insulin-sensitizing drugs offer another potential useful
approach to the treatment of hirsutism.
-Indeed, treatment with metformin and thiazolidinediones
(rosiglitazone, pioglitazone) decreases circulating insulin and
androgen levels in women with PCOS.
- However, a recent systematic review and meta-analysis including 9
placebo-controlled trials concluded that insulin-sensitizing drugs
have no important benefits for the treatment of hirsutism.
- Accordingly, guidelines issued by the Endocrine Society suggest
against their use for the treatment of hirsutism.

55. OTHER TREATMENTS
Gonadotropin releasing hormone agonists
Glucocorticoids
Eflornithine Hydrochloride

56. GONADOTOPIN RELEASING
HARMONE AGONIST
In women with severe hyperandrogenism who fail to respond to or cannot
tolerate treatment with estrogen-progestin contraceptives and antiandrogens,
GnRH agonist therapy can be considered.
GnRH agonists (e.g., leuprolide, nafarelin, goserelin) are not recommended for
routine use, primarily because they induce a severe hypoestrogenism, but also
because they are more costly and inconvenient to use.
Serum androgen levels decrease dramatically during GnRH agonist treatment,
typically falling to near castrate levels within as little as a month.
The addition of estrogen to GnRH agonist therapy to eliminate estrogen
deficiency symptoms and prevent bone loss does not diminish its efficacy and
can even increase it.
Cyclic or continuous treatment with estrogen (e.g., 0.3–0.625 mg conjugated
estrogens daily, or equivalent) and progestin (e.g., 5–10 mg
medroxyprogesterone), or an estrogen-progestin contraceptive, can be used.
Combined treatment decreases free testosterone concentrations to lower levels

57. combined treatment with a GnRH agonist + oral contraceptives is no more
effective than treatment with a GnRH agonist alone.
The effectiveness of GnRH agonist therapy relates directly to the suppression of
LH- dependent ovarian androgen production.
Adequate suppression may not be achieved in obese women, as suggested by
the absence of expected estrogen deficiency symptoms. When suspected, the
possibility can be confirmed by measuring the serum estradiol concentration. If
results indicate inadequate suppression, the dose of GnRH agonist therapy
should be increased.
GnRH agonist therapy should be an effective treatment for women with ovarian
hyperthecosis who typically have severe hyperandrogenism.
However, the impact of treatment on their hirsutism can be less than expected,
even when gonadotropin secretion is suppressed profoundly, because most also
have severe insulin resistance, with hyperinsulinemia driving their androgen
production

58. GLUCOCORTICOID
Glucocorticoids are used to suppress endogenous ACTH secretion in the
long-term management of women with classical congenital adrenal
hyperplasia (CAH).
They also have been used for the treatment of hirsutism in women with
the nonclassical, late-onset, form of the disorder, but with limited benefit.
Although glucocorticoids suppress serum adrenal androgen levels
effectively in women with nonclassical CAH, they are less effective than oral
contraceptives or antiandrogens for the treatment of hirsutism.
Consequently, glucocorticoid treatment has even less to offer women with
other causes for hirsutism

59. EFLORNITHINE HYDROCHLORIDE
Eflornithine hydrochloride (13.9% cream) is a topically applied inhibitor of
ornithine decarboxylase, an enzyme active in the dermal papilla that is
essential for hair growth.
it is not a depilatory agent.
In clinical trials, twice daily application produced noticeable improvement in
facial hair growth within a few weeks in the majority of patients.
However, the drug must be used continuously, because hair growth reverts
to pretreatment characteristics within approximately 8 weeks after treatment
is discontinued.
When used in conjunction with laser hair removal, eflornithine produces a
more rapid response than laser treatment alone.
Treatment with topical eflornithine hydrochloride is perhaps best suited for

60. HAIR REMOVAL TECHNIQUES-
Removal of hair by plucking, waxing, shaving, or use of depilatory
agents is common in women with hirsutism, but the results achieved
are only temporary.
Hairs that are plucked again become apparent after approximately
6–8 weeks. Waxing, using melted wax (“hot waxing”) or a liquid wax
(“cold waxing”) can be used on larger areas of the body, but results
last no longer.
Both methods remove the entire hair, but typically not the dermal
papilla. Because shaving removes hair to a level only slightly below
the skin, its results are short-lived and most women will need to
shave again within 1–3 days.
Electrolysis and photoepilation (laser and pulsed light therapies) are
aimed at permanent hair removal.

61. PERMANENT HAIR TREATMENTS
Electrolysis
Laser and Pulsed Light Therapies

63. SUMMARY OF KEY POINTS AND
RECOMMENDATIONS FOR THE
TREATMENT OF HIRSUTISM
1. The response to all medical treatments for hirsutism is relatively slow,
generally requiring 6 months to achieve significant benefits, which
approximates the duration of the life cycle of a hair follicle.
2. The first treatment of choice for hirsutism is a low-dose estrogen-progestin
contraceptive.
3. In patients having an inadequate response to treatment with estrogen-
progestin contraceptives alone, an antiandrogen should be added, with
spironolactone generally being the best choice.
4. The use of GnRH agonists should be reserved for patients who fail to respond
to or cannot tolerate more traditional treatments and should be combined with
sex steroid add-back therapy, which prevents the consequences of
hypoestrogenism and does not diminish the efficacy of GnRH agonist treatment.
5. Permanent hair removal using electrolysis or photoepilation therapies (laser,
pulsed light), when necessary, is best postponed until hormonal suppression

64. REFERANCE
-BEREK AND NOVAKS EDITION- 16TH
-SPEROFFS – EDITION 9TH
- SHAW -9TH EDITION

65. THANK YOU