Semelhante a Understanding Hyper-Androgenism: Diagnosis & Management“Through Case Discussion” Dr. Sharda Jain Dr. Deepti Nabh Dr. Jyoti Agarwal Dr. Jyoti Bhaskar
Semelhante a Understanding Hyper-Androgenism: Diagnosis & Management“Through Case Discussion” Dr. Sharda Jain Dr. Deepti Nabh Dr. Jyoti Agarwal Dr. Jyoti Bhaskar (20)
Addressing the challenge of lack of Sleep in INDIA
Understanding Hyper-Androgenism: Diagnosis & Management“Through Case Discussion” Dr. Sharda Jain Dr. Deepti Nabh Dr. Jyoti Agarwal Dr. Jyoti Bhaskar
1. Understanding
Hyper-Androgenism: Diagnosis &
Management
“Through Case Discussion”
ACNE Hirsutism Alopecia
Dr. Sharda Jain
Dr. Deepti Nabh
Dr. Jyoti Agarwal
Dr. Jyoti Bhaskar
3. Hyperandrogenism
• Androgen excess
– Affects between 5 - 10% of women
in the reproductive age
• Poly-cystic Ovarian Syndrome (PCOS)
– Prevalence @ 80-85%
among women with androgen excess
O Bulent et al. Diagnosis of hyperandrogenism: clinical criteria. Best Practice & Research Clinical Endocrinology & Metabolism Vol. 20, No. 2, pp. 167–176, 2006
4. Hyperandrogenism
• There is considerable heterogeneity in clinical
findings among women with hyperandrogenism
• Clinical Phenotype could change over time even
in a single patient
O Bulent et al. Diagnosis of hyperandrogenism: clinical criteria. Best Practice & Research Clinical Endocrinology & Metabolism Vol. 20, No. 2, pp. 167–176, 2006
5. Clinical Manifestation of PCOD
AAccnnee
OObbeessiittyy
AAccaannttoossisis HHirirssuuttisismm
IRREGULAR
MENSES
IRREGULAR HHAAIRIR L LOOSSSS
MENSES
6. Clinical Signs of hyperandrogenism
• Hirsutism is a
common
manifestation of
hyperandrogenism
.
• Other clinical signs of
androgen excess include
* Acne,
* Seborrhea, and
* Androgenic alopecia.
SAHA
O Bulent et al. Diagnosis of hyperandrogenism: clinical criteria. Best Practice & Research Clinical Endocrinology & Metabolism Vol. 20, No. 2, pp. 167–176, 2006
7. Clinical Signs of hyperandrogenism
• Depending on the
degree of
androgenization,
signs of
• VIRILIZATION might
be observed in the
evaluation of a
patient with
hyperandrogenism
8. HIRSUTISM
• Excessive male-pattern - terminal
hair growth in women
• Affects up to 15% of women
• Results from androgen production
and/or sensitivity of the pilo-sebaceous
unit to androgens
O Bulent et al. Diagnosis of hyperandrogenism: clinical criteria. Best Practice & Research Clinical Endocrinology & Metabolism Vol. 20, No. 2, pp. 167–176, 2006
9. HIRSUTISM
• Observed in 70-80% of patients
with hyperandrogenism
• Leads to significant psychologic
morbidity and can negatively
influence the quality of life.
O Bulent et al. Diagnosis of hyperandrogenism: clinical criteria. Best Practice & Research Clinical Endocrinology & Metabolism Vol. 20, No. 2, pp. 167–176, 2006
12. Ferriman- Gallwey Scale
Modified Ferriman–Gallwey (F–G) hirsutism scoring system. Each of the nine body areas is rated from 0 (absence of
terminal hairs) to 4 (extensive terminal hair growth), and the numbers in each area are added for a total score. A
modified F–G score ≥ 6 generally defines hirsutism
O Bulent et al. Diagnosis of hyperandrogenism: clinical criteria. Best Practice & Research Clinical Endocrinology & Metabolism Vol. 20, No. 2, pp. 167–176, 2006
13. ACNE
• A common disorder of the Pilo-sebaceous
unit
• Commonly used classification - American
Academy of Dermatology, defines it as mild,
moderate and severe.
Yildiz BO: Diagnosis of hyperandrogenism: clinical criteria. Best Pract Res Clin Endocrinol Metab 2006, 20(2):167-176
14. ACNE
• Evidence demonstrates a CLOSE ASSOCIATION
between Androgen & development of acne
• Has a MULTIFACTORIAL ETIOLOGY in which
androgens, skin lipids, inflammatory signals,
appear to be involved
Acne as an isolated symptom might not be
considered a sign of hyperandrogenism
Yildiz BO: Diagnosis of hyperandrogenism: clinical criteria. Best Pract Res Clin Endocrinol Metab 2006, 20(2):167-176
15. Types of Acne
Comedonal
(non-inflammatory)
Whitehead (closed): a
dilated hair follicle filled
with keratin, sebum, and
bacteria, with an
obstructed opening to the
skin.
Blackhead (open): a
dilated hair follicle filled
with keratin, sebum, and
bacteria, with a wide
opening to the skin capped
with a blackened mass of
skin debris.
Papulo-pustular
(inflammatory)
Papule:
Pustule:
Nodular
(inflammatory)
Nodule: bump
greater than
5mm in diameter.
17. Investigation Protocol
• Patients with severe
hirsutism and REGULAR
MENSES
– Testosterone
– DHEA-S
– Early morning 17-OH
progesterone
• Patients with severe
hirsutism and
IRREGULAR MENSES
– Testosterone
– DHEA-S
– Early morning 17-oH
progesterone
– FSH, LH & PRL
PELVIC USG TO BE IDEALLY PERFORMED
Davis S. Austr Fam Physician 1999;28:447-451
18. Summary
of Suggested Lab Test by
ACOG
Prolactin level
Testosterone level
LH and FSH
TSH
Fasting glucose level or 2 hr OGTT
Lipid profile, including total, LDL,HDL
17-hydroxyprogesterone level*
*--Fasting level to r/o CAH
19. Bio chemical and Diagnostic Markers of
PCOD
Accepted everywhere
– Elevated androgen (i.e. testosterone > 60 or free
testosterone >0.75) levels
– Elevated LH:FSH ratio > 2:1
– Increased Insulin levels ( Not needed)
– Insulin resistance , (Clinical / Lab)
Lab diagnosis of insulin resistance is not needed
–Ultrasound appearance of PCO
20. Ultrasound
Rotterdam Criteria
• In one or both ovaries
Ovarian volume
> 10 ml
• 12 follicles, 2-9 mm in diameter
• Echo dense stroma
Typical “Black Pearl” Necklace
21. Screening Tests For PCOD
ACOG Recommendation
• ACOG recommends that all women with a
suspected diagnosis of PCOD should be
screened with
17-hydroxyprogesterone
level to R/O late onset CAH (Level C).
• PCOD and late onset CAH are
distinguished from each other only by
laboratory testing.
22. A Lab Tests suggested for
SUDDEN onset of Hyperandrogenism
Test Result
Total testosterone level Slightly elevated in PCOS
Total testosterone > 200 ng/dL -- suspicious for adrenal or ovarian tumor
therefore additional evaluation with pelvic US, CT or MRI indicated
Serum DHEAS level Slightly elevated in PCOS
DHEAS level > 8 ng/ml -- suspicious for adrenal tumor therefore additional
evaluation should include adrenal gland imaging with CT or MRI
24 hour urine cortisol or overnight dexamethasone
Urine free cortisol >20 ug/d is suggestive of
Cushing’s Syndrome
23. PCOS – Diagnostic Criteria
NIH 19901 Rotterdam 20031 AE*-PCOS Society
20061,2
If both the criteria are
met:
•Chronic anovulation
•Clinical and/or
biochemical signs of
hyper-androgenism
(with exclusion of
other etiologies, e.g.,
congenital adrenal
hyperplasia)
If two of three
criteria are met:
•Oligo- and/or
anovulation
•Clinical and/or
biochemical signs of
hyperandrogenism
•Polycystic ovaries
*AE: Androgen Excess
If both the criteria are
met (after excluding
other androgen excess
or related disorders a):
•Clinical and/or
biochemical signs of
hyperandorgenism
•Ovarian dysfunction
(Oligo-anovulation
and/or polycystic
ovarian morphology)
NIH: National Institute of Health, AE-PCOS:
Androgen Excess- Polycystic Ovarian Syndrome
1. National institutes of health evidence-based methodology workshop on polycystic ovary syndrome december 3–5, 2012
2. Azziz et.al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report , Fert. Stert.; 91(2): 456-
24. EExxcclluussiioonn ooff RReellaatteedd DDiissoorrddeerrss
• Thyroid disorders
SSrr..TTSSHH,,SSrr..PPrrll
• Hyperprolactinemia
• Cushing’s syndrome
DDeexxaa ssuupprreessssiioonn tteesstt
• Late onset congenital adrenal hyperplasia (CAH)
• Basal morning 17-OHP,(2-3 ng/ml))
• Ovarian and adrenal tumors DHEAS
• WHO I &III –FSH,LH,E2
• Syndromes of severe insulin resistance(HAIRAN
syn)
26. Case 1
• A 23 year old woman presents to a
gynecologist with irregular cycles
• Vitals etc. found within normal Limits
• A USG check advised- Cyst found @ 8; size 6
mm average
• Diagnosis - ? PCOS
27. What percentage of normal women may have
USG finding akin to PCOS?
• Answer -- 25%[1]
• Typical USG Finding of PCOS-
“Pearl Necklace” [1]
• Points for PCOS Dx on USG[2]
– Peripheral location of cysts
– Ovarian Size (>10 cc)
– Follicles similar size
– Hyper-echoic central stroma
• S/o Hyperandrogenism
1 Turrentine et al clinical protocols in gynecology. Informa healthcare. UK London. section PCOS Pg 291 2008
2Atiomo WU, Pearson S, Shaw S et-al. Ultrasound criteria in the diagnosis of polycystic ovary syndrome (PCOS). Ultrasound Med Biol. 2000;26 (6): 977-80
28. PCOS – Diagnostic Criteria
NIH 19901 Rotterdam 20031 AE*-PCOS Society 20061,2
If both the criteria are
met:
•Chronic anovulation
•Clinical and/or
biochemical signs of
hyper-androgenism (with
exclusion of other
etiologies, e.g., congenital
adrenal hyperplasia)
If two of three criteria
are met:
•Oligo- and/or
anovulation
•Clinical and/or
biochemical signs of
hyperandrogenism
•Polycystic ovaries
If both the criteria are met
(after excluding other
androgen excess or related
disorders a):
•Clinical and/or biochemical
signs of hyperandorgenism
•Ovarian dysfunction (Oligo-anovulation
and/or
polycystic ovarian
morphology)
1. National institutes of health evidence-based methodology workshop on polycystic ovary syndrome december 3–5, 2012
2. Azziz et.al. The Journal of Clinical Endocrinology & Metabolism 2006;91:4237–4245
*AE: Androgen Excess
a. Possibly excluding 21-hydroxylase-deficient non-classic adrenal hyperplasia, androgen-secreting neoplasms, androgenic/anabolic
drug use or abuse, Cushing’s syndrome, the syndromes of severe insulin resistance, thyroid dysfunction, and hyper-prolactinemia
29. Case 2
• A 22 year old females presents with
hirsutism; onset insidious (@7-8 months)
• F/H/O: paternal aunt was Dx with PCOS
• FG score is 12
• Diagnosis – PCOS?
30. Is Family History Important?
– Sisters – 50%
– Maternal – 35%
– Paternal – 80%
Suggest X-linked dominant or autosomal
dominant transmission
Turrentine et al clinical protocols in gynecology. Informa healthcare. UK London. section PCOS Pg 291 2008
31. Evaluation
• Lab Test: Total Testosterone and DHEA-S
• Testosterone: If T >200ng/ml indicates a
testosterone secreting tumor
• DHEA-S: Almost entirely by Adrenal glands,
if >700mg/dl indicates adrenal tumor
32. Differential Diagnosis
Diagnosis Incidence Onset Common symptom
PCOS 70% -85 % Insidious Irregular Menses,
Hyperandrogenism, Poly cystic
ovary; Reversed LH/FSH raio
Idiopathic
Hirsutism
5 %–15 % Insidious No other know cause, normal
ovaries and normal androgens
HAIRAN 3 % – 4 % Insidious Subset of PCOS with Insulin
Resistance and acanthosis
nigricans
Adrenal
hyperplasia
1% - 8 % Rapid Family history, Ashkenazi Jew
(1:27), 17-HP levels before
and after corticotropin test
Ovarian androgen-secreting
tumors
0.3 % –0.1 % Rapid Total T >200 ng/dl and does not
respond to treatment
Drug-induced 0.5 % - 1.0 % Known
onset
Related to medications (steroids,
Danazol, minoxidil etc.)
Turrentine et al clinical protocols in gynecology. Informa healthcare. UK London. section PCOS Pg 291 2008
http://www.aafp.org/afp/2012/0215/p373.html
33. Case 3
• 20 y.o. Female patient
• C/O oligo-menorrhea since puberty and
skin problem
• On physical examination:
– Moderate facial acne
– Body hair: Hirsuite
– BMI 28
34. Hirsutism Assessment
FG score of 10 (2 lip, 2 Chin, 2 arms, 2 abdomen and 2 back) +
Sideburns
O Bulent et al. Diagnosis of hyperandrogenism: clinical criteria. Best Practice & Research Clinical Endocrinology & Metabolism Vol. 20, No. 2, pp. 167–176, 2006
35. EVALUATION
• Evaluation (examination/tests):
– TSH, Prolactin, 17 OH P : normal
– Total T : 85 ng/mL [<72 ng/mL]
– Fasting Insulin : 24 mIU/mL [<17 mIU/mL]
– Fasting Glucose 75 mg/dL
• Treatment?
36. Efficacy of the combination ethinyl estradiol and cyproterone
acetate on endocrine, clinical and ultrasonographic profile in
polycystic ovarian syndrome
• A total of 140 (age 24.1+ 4.9 years) premenopausal women with PCOS
and acne, with or without hirsutism treated for 60 cycles with
0.035mg of ethinyl estradiol and 2mg cyproterone acetate
n=37
Effects of ethinyl estradiol/cyproterone acetate on mild
hirsutism
n=38
Effects of ethinyl estradiol/cyproterone acetate on
moderate hirsutism
After 6 months: 6 months of cessation of therapy
Falsetti L et al. Efficacy of the combination ethinyl estradiol and cyprotarone acetate on endocrine, clinical and ultrasonographic profile in polycystic ovarian syndrome, Hum. Reprod.
2001; 16(1): 36-42
37. Efficacy of the combination ethinyl estradiol and
cyproterone acetate on endocrine, clinical and
ultrasonographic profile in polycystic ovarian syndrome
n=140
Effects of ethinyl estradiol/cyproterone acetate on
treatment on acne
Effects of ethinyl estradiol/cyproterone acetate on severe
hirsutism
n=33
• All Patients with mild and moderate hirsutism completely recovered, while severe hirsutism
improved in mild-moderate form on 81.8% of cases and persisted as severe in 18.2%
• Regardless of its severity, acne disappeared within 12-24 treatment cycles
• The Efficacy of the EE/CPA pill on acne and hirsutism was related to the duration and
continuity of the treatment and to the degree of hirsutism
Falsetti L et al. Efficacy of the combination ethinyl estradiol and cyprotarone acetate on endocrine, clinical and ultrasonographic profile in polycystic ovarian syndrome, Hum. Reprod.
2001; 16(1): 36-42
38. CASE 4
• 20 y.o. Female patient
• C/O irregular menses for past 1 year
• On physical examination:
– Mild facial acne
– BMI 25
• USG: multiple cysts in both the ovaries ranging
from 2-8mm diameter
39. CASE 4
• Evaluation (examination/tests):
– TSH, Prolactin : normal
• Treatment?
40. Efficacy and safety of 3 mg drospirenone/20 mcg
ethinylestradiol oral contraceptive administered in 24/4
regimen in the treatment of acne vulgaris: a randomized,
double-blind, placebo-controlled trial
• A randomized, double-blind, placebo-controlled study was conducted
at 32 centers in the USA to evaluate the efficacy and safety of the 3 mg
drsp/20 mcg EE 24/4 COC for the treatment of moderate acne vulgaris
• 534 women meeting the inclusion criteria were randomized to receive:
– A placebo (n=268)
– 3 mg Drospirenone (drsp) /20 mcg Ethinyl Estradiol (EE) combination in 24/4
regimen (n=266)
Inclusion criteria: Women of reproductive age requiring treatment for moderate acne and
who had a minimum of 40 facial acne lesions (at least 20 inflammatory and 20 non-inflammatory)
were eligible for enrollment
Koltun et al, Contraception 77 (2008) 249–256
41. RESULTS
• The inflammatory, non-inflammatory and total lesion counts, the percentage
reductions from baseline to study end point were greater for the COC
group than for the placebo group.
Greater reduction in all lesion counts in the 3 mg drsp/20 mcg EE
24/4 regimen COC group was observed by Cycle 3 of treatment
and was maintained throughout the rest of the study duration
Koltun et al, Contraception 77 (2008) 249–256
42. Results
• Age subgroups showed reduction
in lesion counts with the COC was
generally greater in the younger
age groups relative to placebo
• Subjects aged 14–22 years
exhibited the largest between-group
differences for reductions in
inflammatory lesion count.
• Subjects in the age range of 35 to 45
years in COC subgroup had the
highest percentage of subjects
who had a rating of ‘clear’ or ‘almost
clear’ on the ISGA assessment scale
compared to placebo
Overall, the different age groups responded to treatment either
through lesion counts or ISGA rating in varying degrees.
Koltun et al, Contraception 77 (2008) 249–256
43. CONCLUSION
The 3 mg drsp/20 mcg EE in 24/4 regimen was
significantly more effective than placebo in treating
moderate acne vulgaris and these anti-acne effects could
be observed by Cycle 3 of treatment.
Koltun et al, Contraception 77 (2008) 249–256
44. CASE 5
• 23 y.o. Female patient about to get married
within a month. Seeks advice on contraception.
• Regular menses ranging from 26-30 days
• On physical examination:
– Mild facial acne
– Reports to have undergone laser hair removal and
waxing recently
– BMI 22
46. Randomized comparative study
20EE/150DSG vs 20EE / 3000 DRSP
Results of a randomized comparative study involving 386
women aged 18 – 35 for 7 cycles with either of the two OC
use
•20mcg ethinyl estradiol + 150mcg desogesrtel (n=221)
•20mcg ethinyl estradiol + 3mg drospirenone (n=220)
Doris M Gruber et al. Treat Endocrinol 2006;5:115 – 121
47. RESULTS
Group Pearl Index 95% CI
DSG/20EE
(n = 221)
Doris M Gruber et al. Treat Endocrinol 2006;5:115 – 121
0.95 0.0 – 5.3
DRSP / 20EE
(n = 220)
0.95 0.0 – 5.3
Efficacy: Pearl Index
Cycle Control
Effect on weight Satisfaction
48. CCOONNCCLLUUSSIIOONNSS
• Both treatments are effective, safe and well-tolerated
• Both treatments had high user satisfaction and
cycle control
• Both treatments had a negligible affect on body
weight
49. ADDRESS
11 Gagan Vihar, Near Karkari Morh
Flyover, Delhi - 51
CONTACT US
9650588339, 011-22414049,
WEBSITE :
www.lifecarecentre.in
www.drshardajain.com
www.lifecareivf.com
E-MAIL ID
Sharda.lifecare@gmail.com
Lifecarecentre21@gmail.com
info@lifecareivf.com
&
Notas do Editor
Presence of hirsutism is generally determined by the Ferriman–Gallwey hirsutism score. Ferriman and Gallwey described this subjective assessment, which scores the presence of hair growth between 0 (absence of terminal hairs) and 4 (extensive terminal hair growth) at 11 different body sites (upper lip, chin, chest, upper and lower back, upper and lower abdomen, arm, forearm, thigh, and lower leg).
Hatch et al18 suggested a method scoring 9 of the 11 body areas originally assessed by Ferriman and Gallwey, excluding the less androgen sensitive areas of lower legs and lower arms. A modified F–G score ≥ 6 generally defines hirsutism.
O Bulent et al. Diagnosis of hyperandrogenism: clinical criteria. Best Practice & Research Clinical Endocrinology & Metabolism Vol. 20, No. 2, pp. 167–176, 2006
Testosterone needed if considering treatment with antiandrogen for hisuitism as levels can then be followed.
DHEAS not needed.
Fasting morning 17-hydroxyprogesterone
Levels &gt; 800 ng/dL (8ng/ml) highly suspicious for late-onset congenital adrenal hyperplasia (CAH)
Levels between 200-800 ng/dL (2-8ng/ml) unclear
Levels &lt; 200 ng/dL (2ng/ml) usually no CAH
A ratio of less than 4.5 of fasting glucose to insulin levels correlates significantly with insulin resistance and has been studied for use as a screening test in obese patients with PCOS. Suggested only in selected patients. Information from Legro RS. Polycystic ovary syndrome: current and future treatment paradigms. Am J Obstet Gynecol 1998;179:S101-8.
A ratio of less than 4.5 of fasting glucose to insulin levels correlates significantly with insulin resistance and has been studied for use as a screening test in obese patients with PCOS
PCOS diagnostic criteria:
As per NIH (National Institute of Health) 19901: Chronic anovulation with clinical and/or biochemical signs of hyperandrogenism
As per Rotterdam 2003 classification1: two out of three of the following criteria?: Oligo/anovlaion, clinical and biochemical signs of hyperandrogensim and polycystic ovaries
As per Androgen-excess1,2: Clinical and or biochemical signs of hyperandrogenism with ovarian dysfunction however after excluding other androgen excess disorders.
National institutes of health evidence-based methodology workshop on polycystic ovary syndrome december 3–5, 2012
Azziz et.al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report , Fert. Stert.; 91(2): 456-488
Point to note for women on OCPs- 14% may present with picture similar to PCOS
Presence of hirsutism is generally determined by the Ferriman–Gallwey hirsutism score. Ferriman and Gallwey described this subjective assessment, which scores the presence of hair growth between 0 (absence of terminal hairs) and 4 (extensive terminal hair growth) at 11 different body sites (upper lip, chin, chest, upper and lower back, upper and lower abdomen, arm, forearm, thigh, and lower leg).
Hatch et al18 suggested a method scoring 9 of the 11 body areas originally assessed by Ferriman and Gallwey, excluding the less androgen sensitive areas of lower legs and lower arms. A modified F–G score ≥ 6 generally defines hirsutism.
O Bulent et al. Diagnosis of hyperandrogenism: clinical criteria. Best Practice & Research Clinical Endocrinology & Metabolism Vol. 20, No. 2, pp. 167–176, 2006