| PCOS Polycystic Ovary Syndrome - Anovulatory Androgen Excess
by Jeffrey Dach MD
This article is Part One of a series,
For Part Two, Click Here.
year old Alice has PCOS (Polycystic Ovary Syndrome). Alice came
with her Mom into the office and told me her story. Alice has been
overweight, borderline diabetic, and has facial hair and acne caused by
elevated testosterone. At age 12, Alice started normal menstrual
cycles, but her cycles began fluctuating and periods stopped at age 15.
Her gyne doctor diagnosed PCOS (Polycystic Ovary Syndrome), and put her
on birth control pills to regulate her cycles. The birth control pills
caused adverse side effects of weight gain weight and elevated blood
pressure (hypertension), so she stopped them.
Progesterone is the Most Logical Form of Treatment and Actually Works
months ago, Alice was switched over from the birth control pills to
natural progesterone, taking a 100 mg capsule twice a day for 14 days
on, 14 days off. The progesterone was successful, restoring a normal
menstrual period, and a return to regular cycles.
control pills) are usually prescribed by the ob-gyne doctor to regulate
cycles in the PCOS patient. This standard treatment is not the best
one. There is a better more logical alternative that actually works
called natural progesterone. Both John R Lee MD, and JeriLynn Prior
MD advocate the use of natural progesterone as a far better alternative
to birth control pills. After all, birth control pills (BCP's) are a
chemical form of castration, and work by inhibiting ovulation.
article will explain the cause of PCOS, and will describe the signs and
symptoms of PCOS, including the clinical features of PCOS, and give you
a simple questionnaire to determine if you have PCOS. This article will
also explain why natural progesterone is the best treatment, and a
much better choice compared to birth control pills.
PCOS was Rare When First Described in 1935, Now Quite Common.
PCOS (polycystic ovary syndrome) was first described in 1935 by Stein
and Leventhal, it was fairly rare.(55) Nowadays, it is quite common,
involving 6 to 10 per cent of the female population, affecting 3.5 to 5
million women. (24) Why the increased incidence? Some believe that endocrine disruptor chemicals in the environment are to blame.(60A)
Clinical Signs and Symptoms Of PCOS
Oligomenorrhea or amenorrhea (no periods), Anovulation (no ovulation)
Weight gain, obesity, Hirsutism (excessive hair growth, male pattern)
resistance (pre-diabetes), Acne, Male-pattern baldness, Multiple small
ovarian cysts on sonogram, Acanthosis Nigrans (darkening of the skin at
the nape of the neck and under arms)-indicator of hyperinsulinemia
Above Left Image: Obese Young Lady with PCOS, anovulatory infertility, acne and facial hair.
A Brief Moment for Definitions:
Definition of ovulation: This
is the when an egg pops out of the follicle in the ovary, and starts on
the long trip down the fallopian tube to the uterine cavity where it
can be fertilized to form a new baby. Ovulation causes high progesterone
production by corpus luteum in the ovary. Menstrual Cycles are regular.
Definition of Anovulation: The egg doesn't’t pop out and there is no progesterone production. The cycles are irregular or absent.
Above Left Image: Typical hirsutism, with hair growth under the chin.
How Do You Know If You Have PCOS?
This is the PCOS Questionnaire.(63)(64) and these are the Links to questionnaire articles:
1) PCOS Questionnaire
2) PCOS questionnaire
If you answer Yes, to 2 out of 3 of the following questions, this indicates high likelihood (80%) of PCOS.
Above Left Image: The bearded fat lady at the circus. She had PCOS.
Length of Menstrual Cycle, Variable Length
1) Between the ages of 16 and 40, was length of your menstrual cycle (on average) greater than 35 days and/or totally variable ?
Hair Growth (Male Pattern)
your menstruating years (not including during pregnancy), did you
have dark, coarse hair on your three or more of these sites? Upper lip?
chin? breasts? chest between the breasts? back? belly? upper arms? upper
3) Were you ever obese or overweight between the ages of 16 and 40?
Hormone Levels during the Menstrual Cycle with normal ovulation.
The green dotted line is progesterone which rises days 14-22.
The progesterone is absent in PCOS, because there is no ovulation,
and the green line stays flat on the chart, instead of rising
What Causes PCOS ?
world’s greatest authority, Leon Speroff MD, says: “A question which
has puzzled gynecologists and endocrinologists for many years is what
causes polycystic ovaries. There is an answer which is appealing in its
logic and clinical applicability. The characteristic polycystic ovary
emerges when a state of anovulation persists for any length of time”
(1) Clinical Gynecologic Endocrinology and Infertility by Leon Speroff MD p.493
is the end result of not ovulating, (no progesterone production) for a
long time (a few years), resulting in a vicious cycle which self
perpetuates anovulation, causing increased testosterone production by
the ovary. Insulin resistant diabetes and obesity aggravate the
problem. As you might expect, PCOS is a major cause of infertility.
10% of patients thought to have PCOS actually have an underlying
genetic enzyme defect in adrenal steroid synthesis called Non-Classical
CAH. This can be diagnosed with a Cortrosyn stimulation test, and a
21-OH genetic test called CAHDtex from Esoterix. If present, treatment
is successful with low dose adrenal steroid tablets (cortef,
dexamethasone, prednisone) which restores fertility and reverses the
acne. (see below discussion on non-classical CAH).
Oral Contraceptives for PCOS (BCP's)
control pills are a chemical form of castration, which prevent
ovulation. Lack of ovulation is the primary defect in PCOS, so birth
control pills merely perpetuate the primary defect. Birth control pills
can restore regular bleeding periods, however, this is artificial, and
aggravate the underlying PCOS problem rather than solve it. In addition,
birth control pills are known to worsen insulin resistance and
may affect between 3.5 and 5.0 million young women in the United
States, it arguably may be the most important general health issue
affecting young women. BCP's (OCPs) are the traditional therapy for the
chronic treatment of PCOS…… limited evidence raises the issue that BCP's
(OCPs) may aggravate insulin resistance and exert other untoward
metabolic actions that possibly enhance the long-term risk for diabetes
and heart disease."
JeriLynn Prior MD Says:
fundamental problem with PCOS is not making progesterone for two weeks
every cycle. This lack of progesterone leads to an imbalance in the
ovary, causes the stimulation of higher male hormones and leads to the
irregular periods and trouble getting pregnant. Progesterone is usually
missing—replacing it therefore makes sense. “
John R Lee MD says:
recommend supplementation of normal physiologic doses of progesterone
to treat PCOS. If progesterone levels rise each month during the luteal
phase of the cycle, as they are supposed to do, this maintains the
normal synchronal pattern each month, and PCOS rarely, if ever, occurs.
Natural progesterone should be the basis of PCOS treatment, along with
attention to stress, exercise, and nutrition.
If you have PCOS,
you can use 15 to 20 mg of progesterone cream daily from day 14 to day
28 of your cycle. If you have a longer or a shorter cycle, adjust
accordingly. The disappearance of facial hair and acne are usually
obvious signs that hormones are becoming balanced, but to see these
results, you'll need to give the treatment at least six months, in
conjunction with proper diet and exercise." This is quoted from the The John R Lee Medical Letter 1999.(10)
Self-Medication Not Recommended
young women find out about progesterone on internet messenger boards,
and then proceed on their own to buy it over-the-counter. The
progesterone cream may successfully restores cycles in many cases.
However, self - medication is not recommended. It is best to work with a
knowledgeable physician. If you have PCOS and need a doctor to
prescribe progesterone, you can find a knowledgeable physician on the ACAM or A4M doctor's directory.(65)(66) Always work closely with a knowledgeable physician.
Can PCOS be Treated with Natural Progesterone?
YES by Dr. Jerilynn Prior (3)
talks back to the hypothalamic and pituitary (brain) hormones that
control the ovaries and stops them from stimulating the ovaries to make
too much testosterone." Above quote is attributed to Jerilyn Prior MD Web Site.(3)
Dr Prior recognizes that the (BCP) pill,
with its synthetic type of progesterone, does help women with PCOS to a
But her goal for PCOS patients is, "to return the brain/ovary system to a normal balance. The goal of the BCP Pill is the opposite - it must suppress the brain-ovary system to prevent pregnancy."
To help her PCOS patients achieve a normal hormonal balance, she prescribes oral micronized progesterone (trade
name Prometrium) which is a bio-identical hormone. Taking this natural
progesterone for two weeks every month (called cyclic progesterone
therapy) may help the brain to develop the normal cyclic rhythm that is
missing in PCOS.
Interestingly, Dr. Prior believes there is
another benefit of cyclic progesterone therapy. She explains, "most
doctors don't realize progesterone antagonizes and inhibits the enzyme
(called 5-alpha reductase) that is needed to make testosterone into
dihydrotestosterone. Dihydrotestosterone is the powerful male hormone
that talks hair follicles into making coarse hair and too much oil that
WHAT MAKES YOUR OVARIES TICK Insights about Ovulation, Fertility, PCOS and more. (4)
Click Herer for an Interview
with Jerilynn C. Prior, M.D. posted on the Virgina Hopkins Health
Watch. Dr. Jerilynn Prior is a professor of endocrinology at the
University of British Columbia. She is a pioneer in research involving
women's menstrual cycles, ovulation, progesterone and bone loss.
Above Left Image: Polycystic ovary on ultrasound image.
Interview Quoted from Virgina Hopkins Health Watch:
JLML: How do you track your luteal phase with a basal temperature chart? The above interview posted courtesy of Virginia Hopkins Health Watch. (4)
If you record your oral temperature every morning for an entire month
using a digital thermometer, record the temperature in the evening
before you go to bed, and record any illness or early or late rising,
you can quantitatively determine which days of the cycle are high
progesterone days. You can then take all of those daily temperatures
from the beginning of one period until the day before the beginning of
the next, and do an average of the temperatures. The point where your
temperature goes above that average, and stays above it, is the
beginning of the luteal phase. It will go back down when your period
starts or just before. That's how easy it is to figure out your luteal
phase length! That alone is valuable information for women who are
having miscarriages that may be due to a short luteal phase.
JLML: I have found that women who are more aware of their cycles are often better able to self-treat for hormone imbalances.
What else can you tell us about anovulatory cycles? The other kind of
ovulation disturbance I called “turned on.” The woman experiencing this
kind of ovulation disturbance will complain of weight gain, acne, and
hair where she doesn’t want it. The biology of this is less clear, but
it relates to insulin excess and insulin resistance, which have effects
both on the brain by increasing LH (luteinizing hormone) levels, and
directly on the ovary. Excess insulin sits on receptors on the theca
cells, the outer coat of the ovary, and makes them more responsive to
the hormonal environment, and therefore they make more androgens
[testosterone, male hormones].
JLML: Aha! So that's why a high
sugar diet aggravates polycystic ovary syndrome. The excess sugar
creates high insulin levels, which stimulate androgen production in the
ovary, which suppresses ovulation.
JCPrior: The higher LH and
the higher androgen levels set up a signal that inhibits the follicle
from ovulating. Because each follicle grows and creates a lake of fluid
around it, if it doesn’t burst and release its egg, a cyst is left.
Therefore you get into a situation of high or normal estrogen levels,
high androgens, and low progesterone. That condition is usually
characterized by obesity, especially middle-of-the-body obesity,
androgen signs such acne, oily skin, facial and breast hair, and head
hair loss. Because estrogen tends to be higher with weight gain, these
are the women who have a higher breast cancer and endometrial cancer
risk. They may also have the worst PMS symptoms.
JLML: So this is yet another good reason to avoid sugar and refined carbohydrates such as white bread and pasta.
And it's another good reason to get plenty of aerobic or endurance-type
exercise, which is one of the best ways of getting the insulin levels
down and decreasing PMS. With turned on ovulation disturbances you need
to correct three problems: The first is to bring progesterone into
balance –and for this you use physiologic doses of progesterone. Next,
you often you need to block the effect of the male hormone. There's a
medicine called spironolactone which I use that blocks androgen action
at the cell level. Finally, if a person has a family history of diabetes
or is quite obese, then I may use a drug called metformin (Glucophage)
that sensitizes the body to insulin and allows the insulin levels to go
JLML: I have found that supplemental progesterone, a good amount of exercise, and a low sugar diet, low simple carbohydrate and low fat diet with plenty of vegetables will often restore balance.
Help for PCOS - Cyclic Progesterone Therapy
by Dr. Jerilynn C. Prior and Celeste Wincapaw (5)
Jerilynn C. Prior MD Says:
I use cyclic progesterone therapy as the heart of treatment for PCOS- anovulatory androgen excess.(6) Progesterone is the hormone made by the ovary after an egg is released.
fundamental problem with PCOS is not making progesterone for two weeks
every cycle. This lack of progesterone leads to an imbalance in the
ovary, causes the stimulation of higher male hormones and leads to the
irregular periods and trouble getting pregnant. Progesterone is usually
missing—replacing it therefore makes sense. Progesterone talks back to
the hypothalamic and pituitary (brain) hormones that control the ovary,
and stops them from stimulating the ovary to make too much testosterone.
Taking progesterone for two weeks every month (called cyclic
progesterone) may help the brain to develop the normal cyclic rhythm
that is missing in PCOS. Progesterone also counterbalances the steadily
high estrogen levels that the PCOS ovary produces even if you have no
periods. Progesterone will prevent estrogen over-stimulation of the
uterine lining (endometrial hyperplasia) and heavy flow. It may also
interfere with the action of high estrogen on the breasts, therefore
preventing tenderness and “lumpiness” and perhaps even the risk for
Finally, and most doctors don’t realize this,
progesterone antagonizes and inhibits the enzyme (called 5-alpha
reductase) that is needed to make testosterone into dihydrotestosterone.
Dihydrotestosterone is the powerful male hormone that talks hair
follicles into making coarse hair and too much oil that causes acne.
Useful Tools for Patients:
Protocol for Cyclic PROGESTERONE THERAPY patient handout sheet (6)
Menstrual cycle diary log sheet patient handout (7)
Guidelines for Progesterone Cream Dosage for PCOS (8)
Early PCOS - 32mg from day 12-26
Advanced PCOS - 54mg from day 12-26 of your cycle
Severe PCOS with pain,
64mg of progesterone cream from day 5-26 , to address pain from
endometriosis. Then try to wean back to a lesser dose or to extend
breaks to fall into line with a day 12-26 cycle. Note, if you are using a
regime day 5-26 in the first 4-7 months until symptoms settle, please
be aware you are using a program suggested to enhance fertility. (8)
Dr. Lam Progesterone Guidelines for Polycystic Ovary Syndrome (9)
Dr. Lam follows Dr John R Lee pioneering use of progesterone.
20 mg of progesterone cream during day 14 to 28 of the menstrual cycle.
Adjust accordingly if for longer or shorter cycle. As the hormonal
balance is regained, facial hair and acne, two commonly associated
symptoms, will disappear. (9)
Other treatable causes of anovulation
Low thyroid function (hypothyroid) causes menstrual irregularity,
anovulation and infertility. Ovulation and fertility is restored by
thyroid medication. Ovarian cysts also resolve.
2) Vitamin D deficiency is associated with anovulation. Resolves with Vitamin D.
3) Iodine deficiency causes ovarian cysts and anovulation, reversed by iodine supplementation.
Other Useful Drug Treatments for PCOS:
Issue Drug Treatment
Infertility, anovulation: Clomid clomephine, induces ovulation.
Insulin Resistance: Metformin improves insulin sensitivity.(39)(39A)
Acne, Facial Hair: Spironlactone, Aldactone inhibits testosterone.
PCOS—polycystic ovary syndrome.
Standard diagnostic assessments:
1) History may show: Variable or anovulatory menstrual pattern, obesity, hirsutism, and the absence of breast discharge.
2) Pelvic sonogram may show: 10 or more cysts in each ovary, 'string of pearls'.
The ovaries are generally 1.5 to 3 times larger than normal.
3) Labs may show:
Elevated DHEAs and free testosterone.
Ratio of LH to FSH is greater than 1:1, as tested on Day 3 of the menstrual cycle.
The pattern is not very specific and was present in less than 50% in one study.
Common assessments for associated conditions or risks.
1) Fasting biochemical screen and lipid profile
2-hour oral glucose tolerance test (GTT) in patients with risk factors
(obesity, family history, history of gestational diabetes) and may
indicate impaired glucose tolerance (insulin resistance) in 15-30% of
women with PCOS. Frank diabetes can be seen in 65–68% of women with this
condition. Insulin resistance can be observed in both normal weight and
Lab tests for exclusion of other disorders that may cause similar symptoms:
3) 17-hydroxyprogesterone to rule out 21-hydroxylase deficiency (CAH).
4) Fasting insulin level or GTT with insulin levels (also called IGTT).
5) Fasting Glucose to Fasting Insulin ratio <4.5 is cheaper method
ICD-9 Codes: PCOS ICD-9 256.4 Amenorrhea ICD-9 626.0
This article is Part One of a series, For Part Two, Click Here.
Non Classical CAH Congenital Adrenal Hyperplasia,
also known as Non-Classical 21 Hydroxylase Deficiency (NC21OHD)
CAH or 21 Hydroxylase Deficiency is the most common genetic disease
known, occurring in 1% of New Yorkers, and up to 3% in ethnic groups
such as of Ashkenazi Jews, Hispanics, Italians, and Yugoslavs.(68)
per cent of patients with PCOS actually have Non-Classical CAH. The
underlying genetic defect causes an enzyme deficiency in the adrenal
gland which reduces the ability of the adrenal to make
cortisol. Instead of making cortisol, the adrenal steroid pathways are
shunted towards testosterone causing elevated testosterone and the
typical symptoms of hair growth (hirsutism), and acne and there may also
be menstrual irregularities, anovulation, and infertility.(69)(70)
What is the 21 Hydroxylase Enzyme?
is a key enzyme in the adrenal gland which converts cholesterol into
cortisol. In the Classical form of CAH, the 21 hydroxylase enzyme
(21-OH) is severely deficient with resulting low cortisol levels. In
the Non-Classical form however, the 21 hydroxylase (21-OH) enzyme is
still working fairy well with only a slight reduction in activity, and
cortisol levels are usually normal, while testosterone levels may be
elevated to a variable degree. The Human Adrenal Steroid synthesis
pathways and the adrenal enzymes involved can be understood on this chart from Quest Labs.(71)
How to Make the Diagnosis of Non-Classical CAH? Cortrosyn Stimulation
most definitive diagnosis is done with a Cortrosyn Stimulation test
(0.25 mg) which measures 17-hydroxyprogesterone (17-OHP) at 0 and 60
minutes after SQ injection of the Cortrosyn (ACTH).
This test in simple terms is described here:
a preliminary (baseline ) blood test is done for various hormones
including 17-OH, this is followed by a subcutaneous injection of 0.25 mg
of a drug called Cortrosyn which is a form of ACTH which stimulates the
adrenal glands to make more hormones. An hour (60 minutes) after the
Cortrosyn injection, a post stimulation blood sample is drawn for lab
testing for 17-OH and other hormones.
Patients with Non Classic 21-OH Deficiency typically show 60-min stimulated 17-OHP values between 1,500 and 10,000 ng/dl. This chart
shows how the 17-OHP values cluster at three areas for normal (below
1,500), Non-Classical CAH (1500-10,000) and, and Classical CAH (above
10,000). (72) The Quest Lab testing algorithm is shown here.(73)
Genetic Testing for 21-OH Deficiency
testing is now available and very useful. This test shows whether or
not there is a mutation in the CYP21A2 gene coding for the
21-Hydroxylase Enzyme.(74) The CAHDtex test by Esoterix is useful in showing the exact mutation in the CYP21A2 gene. (75) Once the exact mutation in the CYP21A2 gene is known, refer to this chart to determine the severity of the enzyme defect.(76) Genetic testing of other family members is usually recommended once a sibling is found with the mutation.
Clinical Presentation in Children
children, the signs include premature onset of puberty, cystic acne,
accelerated growth, and advanced bone age. Premature development of
pubic hair may occur as early as 6 months of age (due to elevated
testosterone). The severe cystic acne may be unresponsive to oral
antibiotics and retinoic acid (Accutane).
Although the child may
be taller than the other kids in early childhood, this early growth
spurt finishes early (because of epiphyseal fusion), and final height
ends up shorter than usual. Thus, these kids are tall children but short
Another feature may be male pattern baldness in a female involving the top of the head and sparing the sides.
Teenagers and Young Adults - Major Cause of Infertility
girls may present with features of elevated testosterone such as facial
hair (hirsutism), acne and menstrual irregularities or anovulation.
Young adult females may present with the chief complaint of infertility.
It has been generally recognized that infertility of undetermined cause
in women may be reversed with glucocorticoid (cortef or prednisone)
therapy, which most likely treats an occult Non-Classical CAH Syndrome.
William Mc Jefferies MD successfully treated thousands of such cases (
The Safe Uses of Cortisol).(77)
Treatment of Non Classical CAH with Cortisol Restores Fertility
tablets containing low dose cortisol sucessfully treat Non-Classical
CAH and reverse the symptoms restoring fertility. The cortisol
suppresses ACTH and reduces the testosterone production by the adrenal.
Maria New has followed a large group of 400 patients with Non-Classical
CAH, and she treats them with 0.25 mg dexamethasone at the hour of
sleep, and she notes it takes about 3 months for reversal of acne and
infertility. Hirsutism takes longer to respond, about 30 months.
cost for a dexamethasone tablet is $0.50, and the 3-month treatment
cost is estimated to be $45. Compare this $45 dollars to the infertility
treatment cost of $30,000 for one cycle of in vitro fertilization . Dr.
Maria New says that many patients presenting with infertility actually
have NonClassical CAH, and fertility could be restored
easily with treatment with oral cortisol tablets such as cortef,
dexamethasone, or prednisone. (69)
Before you spend a fortune on in-vitro fertilization for infertility,
it would be prudent to rule out Non-Classical CAH with a simple genetic
test. For more information on CAH, see my article on this topic: A Commonly Missed Cause of Infertility, NonClassical CAH by Jeffrey Dach MD (78)
Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Florida 33314
Link to this article:
The Clinical Gynecologic Endocrinology and Infertility: Leon Speroff MD
A Modern Medical Quandary: Polycystic Ovary Syndrome, Insulin Resistance, and Oral Contraceptive Pills, The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 5 1927-1932
Can PCOS be Treated with Natural Progesterone? Jerilynn Prior, PCOSA Today Newsletter
MAKES YOUR OVARIES TICK, Insights about ovulation, fertility, PCOS and
more.An Interview with Jerilynn C. Prior, M.D. FRCPC
Help for Anovulatory Androgen Excess (AAE)—Challenge PCOS! by Dr. Jerilynn C. Prior and Celeste Wincapaw
INFORMATION FOR WOMEN: CYCLIC PROGESTERONE THERAPY Protocol for treatment.
Menstrual Cycle Diary / Log Book / Calendar
What is the guidelines to progesterone dosage for PCOS ? National Progesterone Advisory Network
Dr. Lam Progesterone Page
Your Dr. May Not Tell You about PCOS, Polycystic Ovary Syndrome (PCOS),
A New Epidemic that Causes Infertility, Excess Hair, Acne and More By
John R. Lee, M.D. and Virginia Hopkins
Letter, Phytotherapy for Polycystic Ovarian Syndrome (PCOS) by Angela
Hywood N.D. & Kerry Bone, Townsend Letter message Boards
PCOS GROUPS and Message Boards, The Arizona Polycystic Ovarian Syndrome Meetup Group,
Hundreds of PCOS Message Boards
Home Ovulation Tests, Pregnancy Test Kits, Basal Thermometers
Birth Control Pills
Birth Control Pill is NOT the Answer. The birth control pill does
absolutely nothing to improve insulin resistance, and can actually
(1). “They may, however, worsen insulin resistance and
lead to deterioration of glucose tolerance.” Glucose tolerance
deteriorated significantly, and two women developed diabetes” In 2003,
the Journal of Clinical Endocrinology & Metabolism published an
article called 'A Modern Medical Quandary: Polycystic Ovary Syndrome,
Insulin Resistance, and Oral Contraceptive Pills'.
(2) The Pill
has been standard treatment for PCOS, and yet, perversely, it appears to
worsen the metabolic problem that is at the root of the condition. The
'...what has been lacking is a critical examination
of whether oral contraceptives might...exert adverse metabolic effects
with long-term consequences..'.
I propose that the Pill has made
additional contributions to the epidemic of PCOS. The Pill is known to
cause permanent hormone changes, even once it is stopped.
Most doctors agree that it can take 1 to 2 years for normal menstrual
cycles to resume after stopping the pill . The pill will cause a monthly
bleed, but this is not a true period.
Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 9
3074-3077. The Effect of a Desogestrel-Containing Oral Contraceptive on
Glucose Tolerance and Leptin Concentrations in Hyperandrogenic Women
Shahla Nader, Maggy G. Riad-Gabriel and Mohammed F. Saad
E et al. A modern medical quandary: Polycystic Ovary Syndrome, Insulin
Resistance, and Oral Contraceptive Pills. J Clin End Met 2003.88(5):
1927-1932 CONTROVERSIES IN ENDOCRINOLOGY Evanthia Diamanti-Kandarakis,
Jean-Patrice Baillargeon, Maria J. Iuorno, Daniela J. Jakubowicz and
John E. Nestler
et al. Impact of Oral Contraceptives on Sex Hormone-Binding Globulin
and Androgen Levels: A Retrospective Study in Women with Sexual
Dysfunction. The Journal of Sexual Medicine. 2006. 3:p.104-113
Birth Control Pill Side effects. Oral contraceptive pill may prevent more than pregnancy
New research indicates birth control pill could cause long-term problems with testosterone
Ditch the Pill . org, very neative about BCPs
Jones, M.D. Medical Director, Women’s Health Institute
Minerva Endocrinol. 2005 Sep;30(3):193-7. Relationship between insulin
secretion, and thyroid and ovary function in patients suffering from
polycystic ovary. CONCLUSIONS: The data obtained in our study enable us
to support the close connection between ovary function, thyroid function
and insulin-resistance. In all patients, in fact, albeit at different
times, an improvement was obtained in all 3 pathologies.
Thyroid disease and female reproduction. Poppe K, Velkeniers B, Glinoer D. Clin Endocrinol (Oxf). 2007 Mar;66(3):309-21
prevalence of autoimmune thyroiditis in patients with polycystic ovary
syndrome.Janssen OE. Eur J Endocrinol. 2004 Mar;150(3):363-9.
CONCLUSION: This prospective study demonstrates a threefold higher
prevalence of Autoimmune Thyroid disorders in patients with PCOS
Prevalence of PCOS in Population
Prospective Study of the Prevalence of the Polycystic Ovary Syndrome in
Unselected Caucasian Women from Spain. Our results demonstrate a 6.5%
prevalence of PCOS, as defined, in a minimally biased population of
Caucasian women from Spain. The polycystic ovary syndrome, hirsutism,
and acne are common endocrine disorders in women. The Journal of
Clinical Endocrinology & Metabolism Vol. 85, No. 7 2434-2438
presenting with polycystic ovary syndrome.Sridhar GR. J Assoc
Physicians India. 1993 Feb;41(2):88-90. During a 30 months period, two
women of primary hypothyroidism (2/13; 1.04%) presented with features of
polycystic ovary syndrome (PCOS). In hypothyroidism, sex hormone
binding globulin levels are decreased; increased conversion of
androstenedione to testosterone, and aromatization to estradiol are
present, all these being an exaggeration of biochemical changes
characteristic of PCOS. Besides, metabolic clearance rates of
androstenedione and estrone, the putative mediators of PCOS, are
reduced. Hypothyroidism can either initiate, maintain or worsen the
syndrome. Correction of hypothyroidism when present, would therefore
form an important aspect in the management of infertility associated
puberty and large multicystic ovaries in young girls with primary
hypothyroidism.Sanjeevaiah AR, Sanjay S, Deepak T, Sharada A, Srikanta
SS. Samatvam Endocrinology Diabetes Center, Bangalore, India.
Med J. 2007 Jul;16(2 Suppl):S60-62. Vaginal bleeding with multicystic
ovaries and a pituitary mass in a child with severe
hypothyroidism.Mohsin F, Nahar N, Azad K, Nahar J. Department of
Paediatrics, Bangladesh Institute of Research and Rehabilitation on
Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka, Bangladesh.
seven year and ten months old girl presented with cyclic vaginal
bleeding and a huge abdominopelvic mass. She had clinical features of
hypothyroidism. The investigation results were consistent with the
diagnosis of primary hypothyroidism with precocious puberty. She also
had bilaterally enlarged cystic ovaries on CT scan of abdomen and CT
scan of brain showed pituitary macroadenoma. After starting treatment
with thyroxine, patient became euthyroid and her general condition
improved. Treatment with thyroxine alone halted the cyclic vaginal
bleeding, led to rapid resolution of the ovarian cysts and regression of
the pituitary mass.
ovarian hyperstimulation syndrome associated with hypothyroidism.
Rotmensch S, Scommegna A. Department of Obstetrics and Gynecology,
Michael Reese Hospital and Medical Center, University of Chicago,
Pritzker School of Medicine, IL 60616. Am J Obstet Gynecol. 1989
May;160(5 Pt 1):1220-2.
puberty and large multicystic ovaries in young girls with primary
hypothyroidism.Sanjeevaiah AR, Sanjay S, Deepak T, Sharada A, Srikanta
SS. Endocr Pract. 2007 Oct;13(6):652-5.
hypothyroidism presenting as ovarian tumor and precocious puberty in a
prepubertal girl.Campaner AB, Scapinelli A, Machado RO, Dos Santos RE,
Beznos GW, Aoki T. Department of Obstetrics and Gynecology, Santa Casa
São Paulo-Faculty of Medical Science, São Paulo, Brazil. Gynecol
Endocrinol. 2006 Jul;22(7):395-8.
We report a case of a
prepubertal girl with juvenile primary hypothyroidism presenting as
ovarian cysts and precocious puberty. The 7-year-old female was referred
to our clinic because of a pelvic/abdominal mass and vaginal bleeding.
Besides these findings, on physical examination we noticed the thyroid
gland globally increased and the presence of secondary sexual
characteristics. Based upon the clinical profile and investigations, the
patient was diagnosed with juvenile primary hypothyroidism due to
autoimmune thyroiditis. The cysts and precocious puberty resolved
spontaneously after the simple replacement of thyroid hormone. It is
important to bear in mind hypothyroidism in cases of girls presenting
ovarian cysts and precocious puberty in order to avoid unnecessary
surgery on the ovaries.
J Pediatr Endocrinol Metab. 2006 Jul;19(7):895-900.
cysts in young girls with hypothyroidism: follow-up and effect of
treatment.Sharma Y, Bajpai A, Mittal S, Ovarian cysts have been reported
in girls with longstanding uncompensated primary hypothyroidism.
Restoration of euthyroid state has been associated with resolution of
these cysts; long-term follow-up of these patients is however lacking.
Our study emphasizes the need to exclude hypothyroidism in young girls
with ovarian cysts. A causal link between hypothyroidism and
spontaneously occurring ovarian hyperstimulation syndrome is suggested
by analysis of data from a patient with myxedema and review of data from
Hypothyroidism and the Empirical use of Armour® Thyroid Alan R. Gaby,
MD . Excellent revierw on subclinical hypothyroidism.
girls (ages 9-16) with severe and longstanding hypothyroidism, nine were
diagnosed by pelvic ultrasound with PCOS. The cysts resolved rapidly
after treatment with thyroid hormone. In another study of hypothyroid
patients with PCOS, administration of thyroid hormone was associated
with normalization of ovulation.23 These observations raise the
possibility that sublaboratory hypothyroidism is a contributing factor
in some cases of PCOS."
Lindsay AN, Voorhess ML, MacGillivray MH. Multicystic ovaries in primary hypothyroidism.Obstet Gynecol 1983;61:433-437. 23.
Ghosh S, Kabir SN, Pakrashi A, et al. Subclinicalhypothyroidism: a determinant of polycystic ovary syndrome.
Iodine and PCOS
Iodine sufficiency of the whole human Guy. E. Abraham M.D.1, Jorge D.
Flechas M.D.2 and John C. Hakala R.Ph.Our preliminary experience with I
supplementation at 12.5 mg/day. Our findings in 3 patients with
Polycystic Ovarian Syndrome (PCOS) confirmed the positive response
observed following supplementation with 10 to 20 mg of potassium iodide
by Russian investigators 40 years ago (62). Prior to I supplementation,
those PCOS patients were olygomenorrheic, menstruating one or twice a
year. Following I supplementation for 3 months, they resumed normal
Listing of Iodine publications at the Optimox Web Site.
Orthoiodosupplementation in a Primary Care Practice Jorge D. Flechas, M.D.
deficiency may cause the ovaries to develop cysts , nodules and scar
tissue. At its worse this ovarian pathology is very similar to that of
polycystic ovarian syndrome (PCOS). As of the writing of this article I
have five PCOS patients. The patients have successfully been brought
under control with the use of 50 mg of iodine per day. Control with
these patients meaning cysts are gone, periods every 28 days and type 2
diabetes mellitus under control.
HelpMyThyroid, George Flechas MD web site
Vitamin D and PCOS
serum 25-hydroxyvitamin D concentrations are associated with insulin
resistance and obesity in women with polycystic ovary syndrome. Exp Clin
Endocrinol Diabetes. 2006 Nov;114(10):577-83. Hahn S et al. Insulin
resistance (IR) and central obesity are common features of the
polycystic ovary syndrome (PCOS). Vitamin D is thought to play a role
in the pathogenesis of type 2 diabetes by affecting insulin metabolism.
Subgroup analysis of lean, overweight and obese women revealed
significant higher 25-OH-VD levels in lean women. Differences remained
significant when women were divided according to their 25-OH-VD levels.
Women with hypovitaminosis D (<9 ng/ml) had higher mean BMI, indices
of IR and leptin levels compared to women with normal serum levels (all
p<0.05). Analysis of vitamin D and biochemical endocrine PCOS
features revealed a significant correlation only between 25-OH-VD and
sex hormone-binding globulin as well as the free androgen index. In
conclusion, in PCOS women, low 25-OH-VD levels are associated with
obesity and insulin resistance .
D and calcium dysregulation in the polycystic ovarian
syndrome.Thys-Jacobs S, Donovan D, Papadopoulos A, Sarrel P, Bilezikian
JP. Department of Medicine, St. Lukes-Roosevelt Hospital Center,
Columbia University, College of Physicians & Surgeons, New York, NY
10019, USA. Steroids. 1999 Jun;64(6):430-5.
Over the past 30
years, numerous studies in invertebrates and vertebrates have
established a role of calcium in oocyte maturation as well as in the
resumption and progression of follicular development. Polycystic ovarian
syndrome (PCO) is characterized by hyperandrogenic chronic anovulation,
theca cell hyperplasia, and arrested follicular development. The aim of
this observational study was to determine whether vitamin D and calcium
dysregulation contribute to the development of follicular arrest in
women with PCO, resulting in reproductive and menstrual dysfunction.
Thirteen premenopausal women (mean age 31 +/- 7.9 years) with documented
chronic anovulation and hyperandrogenism were evaluated. Four women
were amenorrheic and nine had a history oligomenorrhea, two of whom had
dysfunctional bleeding. Nine had abnormal pelvic sonograms with multiple
ovarian follicular cysts. All were hirsute, two had alopecia, and five
had acanthosis nigricans. The mean 25 hydrovitamin D was 11.2 +/- 6.9
ng/ml [normal (nl): 9-52], and the mean 1,25 dihydroxyvitamin D was 45.8
+/- 18 pg/ml. with one woman with a 1,25 dihydroxyvitamin D <5 pg/ml
(nl: 15-60). The mean intact parathyroid hormone level was 47 +/- 19
pg/ml (nl: 10-65), with five women with abnormally elevated parathyroid
hormone levels. All were normocalcemic (9.3 +/- 0.4 mg/dl).
Vitamin D repletion with calcium therapy resulted in normalized menstrual cycles within 2 months for seven women,
with two experiencing resolution of their dysfunctional bleeding. Two
became pregnant, and the other four patients maintained normal menstrual
cycles. These data suggest that abnormalities in calcium homeostasis
may be responsible, in part, for the arrested follicular development in
women with PCO and may contribute to the pathogenesis of PCO.
for the Treatment of the Polycystic Ovary Syndrome John E. Nestler,
M.D. N. Engl. J. Med., January 3, 2008; 358(1): 47 - 54.
PCOS and Metformin (Glucophage)
Diet and Weight Loss
The Natural Diet Solution for PCOS and Infertility Nancy Dunne, ND Bill Slater, MBA
PCOS success stories by Nancy Dunne
Conventional Medical Diagnosis and Treatment of PCOS
Speroff on PCOS: Clinical Gynecologic Endocrinology and Infertility by Leon Speroff MD p.493
question which has puzzled gynecologists and endocrinologists for many
years is what causes polycystic ovaries. There is an answer which is
appealing in its logic and clinical applicability. The characteristic
polycystic ovary emerges when a state of anovulation persists for any
length of time” Should you have a sonogram to make the diagnosis of
PCOS? “From 8-14% of normal women will demonstrate ultrasonographic
findings typical of polycystic ovaries. Ultrasonography as a diagnostic
tool for this condition is unnecessary, and we vigorously discourage its
use for this purpose.”
from Book: Introduction: Polycystic ovary syndrome is an
intergenerational problem. Gabor T. Kovacs and Robert Norman Cambridge
University Press 978-0-521-84849-7 - Polycystic Ovary Syndrome, Second
Karri Lynn "Polycystic Ovary (Stein-Leventhal) Syndrome: Etiology,
Complications, and Treatment". Clinical Laboratory Science. Summer
Polycystic Ovary Disease article in the New York Times
MINIREVIEW, Screening for and Treatment of Polycystic Ovary Syndrome in Teenagers.
Experimental Biology and Medicine 229:369-377 (2004) Darren J. Salmi et al.
Galen, Reproductive Science Centerª of the San Francisco Bay Area,
POLYCYSTIC OVARY SYNDROME (PCOS) Treatment of PCOS: In cases where
ovulation is irregular or absent, medication can be used. The most
common agent is clomiphene citrate (Clomid, Serophene), which is
generally taken daily from days 3-7 of a cycle. Ovarian follicle
development is usually monitored with a combination of home urinary LH
testing, and office ultrasound examination. An intrauterine insemination
is frequently advised because of clomiphene's adverse effect on a
womanÕs cervical mucous quality. Additional endometrial support may be
promoted with the use of progesterone or HCG injections. There is a
mildly increased rate of multiple pregnancy with clomiphene (6-7%) but
there is no increased risk of birth defects. The majority of womn who
conceive on clomiphene will do so in the first 4 cycles. If clomiphene
fails to successfully induce ovulation and/or pregnancy, then a group of
injectable hormone preparations, known as gonadotropins, may be
Medicine & Research Volume 2, Number 1 : 13 -27, 2004, Polycystic
Ovarian Syndrome: Diagnosis and Management Michael T. Sheehan, MD.
Marshfield Clinic. Excellent review of conventional diagnosis and
treatment for PCOS.
and managing Polycystic Ovarian Syndrome (PCOS) by Sam Thatcher, M.D.,
Ph.D. director of the Center for Applied Reproductive Science in Johnson
City, TN,. Conventional Approach.
PCOS: The Hidden Epidemic. a Book by Sam Thatcher MD PhD, Conventional Approach to PCOS.
Polycystic Ovarian Syndrome Last Updated: September 15, 2006, on E-Medicine.
HYPERANDROGENISM, HIRSUTISM AND POLYCYSTIC OVARY SYNDROMEChapter 6 -
Randall B. Barnes, M.D., Adrienne B. Neithardt, M.D. and Suleena K.
Kalra, M.D.November 19, 2003 on Endotext.com
PERSONAL EXPERIENCE Androgen Excess in Women: Experience with Over 1000
Consecutive Patients R. AZZIZ, L. A. SANCHEZ, E. S. KNOCHENHAUER, C.
MORAN, J. LAZENBY, K. C. STEPHENS,K. TAYLOR, AND L. R. BOOTS The Journal
of Clinical Endocrinology & Metabolism 89(2):453–462. All patients
with menstrual or ovulatory dysfunction received BCPs' (OCs) when
possible. Patients with unwanted hair growth and evidence of excess
facial or body terminal hair growth received spironolactone (SPA) (200
mg ; 100 mg/d) in combination with the OC, to minimize the risks of
teratogenicity. SPA was rarely used alone, except in the occasional
hirsute patient who had previously undergone a hysterectomy or tubal
ligation. Other treatment regimens were occasionally used, including
glucocorticoids, insulin sensitizers, GnRH analogs, flutamide,
finasteride, and other estrogen-progestin combinations, alone or in
combination; the majority of these were used as part of clinical trials
Stein IF, Leventhal ML. Amenorrhoea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935;29:181–91.
The Environment, Endocrine Disruptor Chemicals and PCOS
Vallombrosa Consensus Statement on Environmental contaminants and human fertility compromise.
Our Stolen Future, endocrine disruptors in the environment
Pesticides and PCOS
Disruptors as environmental cause of PCOSThe impact of Endocrine
Disruptors on the Female Reproductive System, Stamati and pitsos et al.
Testosterone for Women
Testosterone Treatment: Psychological and Physical Effects in Postmenopausal Women.
Susan R. Davis, M.B.B.S., F.R.A.C.P., Ph.D. Menopausal Volume 9, Number 2, Summer 2001
Diet for PCOS
A complete online book on Diet and Nutrition for PCOS by Nancy Dunn
Glycemic Index Chart - handy and useful.
Questionnaire for PCOS
Table 5 Clinical tool for diagnosis of polycystic ovary syndrome
Fam Physician Vol. 53, No. 6, June 2007, pp.1041 - 1047 , Polycystic
ovary syndrome. Validated questionnaire for use in diagnosis, Sue D.
Pedersen, et al.
Fam Physician. 2007 June; 53(6): 1041–1047. Polycystic ovary syndrome.
Validated questionnaire for use in diagnosis, Sue D. Pedersen, et al.
ACAM doctor's directory
A4M doctor's directory
(67) http://jeffreydach.com/2008/02/27/a-commonly-missed-cause-of-infertility-nonclassical-cah-by-jeffrey-dach-md.aspx A Commonly Missed Cause of Infertility, NonClassical CAH by Jeffrey Dach MD
Non Classical Adrenal Hyperplasia CAH 21-OH Deficiency
FIG. 8. Non-classical CAH 21 Hydroxylase Deficiency Chart of Disease frequencies in different ethnic groups.
The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 11 4205-4214
EXTENSIVE CLINICAL EXPERIENCE, Nonclassical 21-Hydroxylase Deficiency
Maria I. New Department of Pediatrics, Mount Sinai School of Medicine, New York, New York 10029
Consensus Statement on Treatment of 21-Hydroxylase Deficiency. JCEM 87(9):4048-4053, 2002.
Chart showing pathways of steroid synthsis Quest LAbs.
5. Nomogram relating baseline to ACTH-stimulated serum concentrations
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Congenital Adrenal Hyperplasia Testing Algorithm Guide Quest LAbs
21 Hydroxylase Deficiency Common Mutations, Quest LAbs
TESTING FOR 21-HYDROXYLASE DEFICIENCY, Esoterix introduces a new DNA
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TABLE 1. Common gene mutations of the 21-hydroxylase gene CYP21A2 (75 )
Safe Use of Cortisol is a Unique Medical Classic, December 7, 2007 By Jeffrey Dach MD
A Commonly Missed Cause of Infertility, NonClassical CAH by Jeffrey Dach MD
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