John Rocks Error

1

• John Rocks Error
• M. Gladwell
• Rock born in 1890, was in love with the church
• An inventor of the B.C. Pill
• Faith vocation were compatible to him
• Called a moral rapist got a lot of grief from
  many people, including clergy. Rock was unmoved
  John, stick to your conscious
• Pill approved by FDA in 1960
• Very popular in news media, tall man with
  impeccable manners and thought his association
  with pill made it more respectable

2
-Taught OB at Harvard Medical for more than 30
years -Pioneer in in vitro fertilization (IVF)
and freezing sperm cells -Two collaborators on
the pill Gregory Pincus Min-Cheuch Chang
worked out mechanism -Rock guided through
clinical trials gave validity to claim would
prevent pregnancy -Testified before FDA -Examiner
said Catholic church would NEVER approve - Young
man, dont you sell my church short.
3
1968 Pope Paul VI outlawed oral
contraceptives and all other artificial methods
of B.C. John Rock made an Error not
deliberate Became manifest after his death via
science discoveries he couldnt have anticipated.
Error has colored way people thought about
contraception ever since. He believed pill was
natural method of BC because it worked by
natural means Progestin stops ovaries from
producing eggs (prep uterus for implantation)
favors gestation
4
Pregnant women make progestin so egg cant be
released threaten pregnancy Pill progestin
not limited to certain part of cycle (sudden
surge after ovulation) Steady dose so no
ovulation Also little estrogen hold endometrium
together and other tissues Pills ingredients
duplicated what can be found in the body, had
theological significance to ROCK. 1951 Pope
Pius XII sanctioned rhythm method deemed it
natural
5
Rock had Rhythm Method Clinic Limit Sex to safe
period that progestin created Pill using
hormone to extend safe period entire month Rock
an adjunct to nature 1958 Pope approved
Pill for Catholics as long as contraceptive
effects were indirect Led to many arcane
arguments Use Pill to achieve rhythm then why
not Pill alone etc..
6
Rock/Pincus came up with 4 week cycle 3 weeks
hormone 1 week placebo allows for
menstruation THERE WAS AND IS NO MEDICAL REASON
FOR THIS Typical woman 28 day
cycle CYCLE First E, then E P flood the
uterus. Lining thick and swollen to prep for
fertilized egg. Egg not fertilized, hormone
levels drop and lining (endometrium) sloughed off
in menstrual bleed
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Pill no egg released Flux of hormones cause
lining to grow are dramatically reduced Effect
of Pills hormones on endometrium so modest
women could go for months without having to
menstruate a cycle of any desired length could
be produced Pincus 1958 Picked 4 week cycle
so women find menstruating reassuring Rock
wanted to be natural Packaging 28 day
cycle Drug shaped by dictates of Catholic Church
8
That was his error Not so natural after
all ______________________________________________
__________ 1986 Bev Strassman (U Mich) Africa
Dogon tribe in Mali. Use no contraception. Wante
d to construct reproductive profile of women in
tribe to understand female biology before modern
age Evolutionary perspective rather than
theological one Stayed in Tribe for 2.5
years Put menstruating women in huts at the edge
of village Two huts 3 beds in hut, nighttime
hangout (dusk dawn)
9
736 nights monitored huts First period age
16 Gives birth 8 or 9 times Onset of
menstruation ? age 20 has 7 periods a
year 24-34 Pregnant or breast feeding
(suppresses ovulation about 20 months) Average 1
period a year 35-menoapuse (50) average 4
periods a year Menstruate 100 times in life
live to be 70-80 Western Woman 350-400
X Exception two sterile women
10
Number of lifetime menses isnt greatly affected
by differences in diet, climate, method of
subsistence Prevailing factors wet nursing or
sterility What we think of as normal menses
abnormal in evolutionary terms Pity
gynecologists think women have to menstruate
every month Shift 100 ? 400 Periods is
significant incessant ovulation a serious
problem for womens health?
11
Doesnt mean women always better off not
menstruating Failure to menstruate signals
increased risk of uterine cancer in obese
women Female athletes increased risk of
osteoporosis Most women incessant ovulation has
no purpose lots of disadvantages Abdominal
pain, mood shifts, migraines, endometriosis,
fibroids anemia greatly increased, as well as
risk of some cancers Any change promoting cell
growth division increases cancer
risk Ovulation one of those changes
12
Egg bursts through ovary wall Woman gets
pregnant and has child lifetime risk of ovarian
cancer drops by 10 with each kid from saving
ovaries 12 months of cell division Same argument
for endometrial cancer In fact, ovarian
endometrial cancer modern diseases, in part
because of 400 menses? In this sense, Pill has
natural effect restrained cell division 10 year
on Pill reduces ovarian cancer by 70,
endometrial cancer by 60
13
Real promise of the Pill not preserve menstrual
rhythms of 20th century, but could DISRUPT
THEM Some reproductive specialists against 28
day Pill cycle New contraceptive, Mircette cuts
placebo to 2 days Sulak, Texas AM, women stay
on Pill 6-12 weeks before spotting During
placebo week, a number of pill users have pelvic
pain, bloating, swelling, headaches, etcSide
effects of normal menstruation
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1980 81 Pike (USC) went to Japan to study
at Atomic Bomb Casualties Commission Why
Japanese women have 6x less breast cancer than
American women? Japanese not genetically
protected move to US and increase risk Unknown
toxin or virus in west environment Breast
cancer risk in the 30s 40s menopause So if toxin expect increase each
year Also, women had ovaries removed had less
cancer
15
Made sense amount of E P women exposed to in
life effects Breast cancer risk Breast cells
(terminal-duct) where most cancer arises
undergoes cell following exposure to E Mid-late
Menstrual period (when ovaries make lost of P)
cell division even greater 1st menstruation How
old at menopause How much hormone made in
ovaries Weight (fat cells make E)
16
Interestingly, bearing children can be
protective against BC (cells resistant to
mutations in last two trimesters) JAPAN
RESULTS 1st period 16.5 US 14 This
difference alone explains 40 gap between US
Japan BC rates Other factors not different Age
of 1st pregnancy, number of children BUT
WEIGHT Japan 100 lbs US
145 Explains 25 difference
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Also examined blood samples Japan 75 amount
of E as US girls (likely because of LF diet) 3
Factors Explain Gap 1st period, weight, and E
levels Pike says understands BC very well.
Made Pike think of Pill which had potential to
be anti BC treatment Breast different than
Reproductive organs Pike thought progestin
wasnt solution was hormone that caused cell
Pill has no effect on BC
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Problem with Pill Amount of P E to make
effective contraception more than amount to keep
reproductive system healthy excess P E raises
risk of BC Solution GnRHAs disrupts signal
pituitary sends when effect production of sex
hormones Given to men with prostate cancer to
halt T production Girls with precocious puberty
(age 7 or 8) Also women (child bearing age) to
decrease production on E P from OV
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Conventional Pill ? Little Pregnancy Pikes
Pill (GnRHA) ? Little menopause Have to be
inhaled nasally breaks down in the body very
fast Menopause has its risks Need E for strong
heart bones P to keep uterus healthy Add back
enough E P to solve these problems Less than
found in Pill Period 4x a year Testing formula
on women with high risk for BC
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Examine changes with mammograms HUGE
CHANGES Large clumps ? gone 3 women Reducing
cell proliferation Reduce risk with Pike
Protocol? Sweep natural approach aside Risk
of (benefit of ) education for women and not
getting pregnant increase BC ovarian C 23
years of uninterrupted ovulation is a brand-new
phenomenon
21
1963 (after Rocks book published) Vatican
officials met with planned parenthood 1964
summit Notre Dame, looked like church was going
to approve Pill Rock cover on Newsweek Pope
inside Many delays, in 1968, Pope said
NO Known Pill could be a cancer drug maybe
church would have approved.
22
Sad ending Rock didnt live to see Pills
effect on cancer rates Saw (at end of 60s) Pill
wrongly accused of causing blood clots, strokes,
heart attacks Mid 70s-Early 80s Number of
women on Pill decreased 50 Harvard Med took
over his reproductive clinic Pension paid 75 a
year, had to sell house 1971 farmhouse in
NH 1983 last public interview, most gratifying
part of life now
23
Hormone Levels during Menses
LH
FSH
E
P
28
21
14
7
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• The pill doesn't boost breast cancer death risk
• Reuters Health Friday, October 12, 2007
• Survival is no better or no worse among breast
  cancer patients who have used the birth control
  pill
• The findings are "broadly reassuring," Dr.
  Herbert R. Peterson of the UNC-Chapel Hill, one
  of the study's authors "There just doesn't appear
  to be any concern about women using the pill at
  younger ages from the standpoint of breast
  cancer."
• Concerns had been raised about oral
  contraceptives and breast cancer by an analysis
  of 54 studies, published in 1996, which found an
  increased risk of the disease among women
  currently on the pill, Peterson noted.
• Researchers hypothesized that women on birth
  control might have more consistent access to
  healthcare, and thus be more likely to have
  breast cancers detected early, which would mean
  they would have a corresponding reduced risk of
  being diagnosed with advanced disease.

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To investigate, Peterson and his team looked at
use of oral contraceptives and the risk of dying
from breast cancer among 4,292 women aged 20 to
54 who had been diagnosed with the disease. The
researchers found no increased risk of death
associated with use of the pill, duration of use,
or any specific oral contraceptive formulation.
Women currently taking oral contraceptives were
actually at 10 lower risk of dying from the
disease. Another large study conducted in 2002
found no increased risk of breast cancer among
women currently on the pill, Peterson pointed
out. "There are now dozens and dozens of studies
looking at the pill and breast cancer risk, and
when you pull them all together they're broadly
reassuring, both in terms of the risk and in
terms of the risk of mortality," he said in an
interview. The one unanswered question remains
the safety of the pill for women approaching
menopause, given the increased risk of breast
cancer recently identified for menopausal women
taking hormone replacement therapy, Peterson
said. "For healthy women over 40 who don't smoke,
oral contraceptives continue to be an option for
contraception, and for many a good option," he
added. Nevertheless, Peterson said, more research
needs to be done to confirm that the pill is safe
for older women. SOURCE Obstetrics Gynecology,
October 2007.
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21
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The internal female reproductive organs include
the uterus, ovaries, cervix and vagina. These
organs are necessary to produce a successful
pregnancy. To prevent pregnancy, birth control
pills affect how these organs normally function.
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Follicle Stimulating Hormone (FHS) and Lutenizing
Hormone (LH) stimulate the ovary into producing a
ripe egg ready for fertilization by sperm during
a normal ovulation cycle.
28
During a normal menstrual cycle, hormones
stimulate the ovary causing an egg to ripen. The
uterine lining thickens preparing itself for
implantation of a fertilized egg and the cervical
mucus thins to help sperm reach the egg.
29
Estrogen in the body cause the pituitary gland to
release LH stimulating the ovary to produce a
ripe egg.
30
The lower levels of estrogen in birth control
pills suppress FSH and LH "fooling" the pituitary
gland into thinking a woman is pregnant.
Ovulation will not occur- which prevents
pregnancy.
31
The progesterone in birth control pills creates a
thick cervical mucus making it difficult for
sperm to reach the uterus. It also impedes an egg
from attaching itself to the uterine lining
(endometrium) because of changes in the cellular
structure of the lining.
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BC METHODS The birth control method you choose
should take into account your overall health
how often you have sex the number of sexual
partners you have if you want to have children
how well each method works (or is effective) in
preventing pregnancy any potential side effects
your comfort level with using the method
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BC METHODS Continuous Abstinence This means
not having sexual intercourse (vaginal, anal, or
oral intercourse) at any time. It is the only
sure way to prevent pregnancy and protect against
HIV and other STDs. This method is 100 effective
at preventing pregnancy and STDs. HIV/AIDS
Louisiana has a serious HIV/AIDS problem. In
2003, the state was in 6th place nationally in
AIDS case rates per 100,000 population, and
11th.in the number of AIDS cases reported,
according to the Center for Disease Control and
Prevention. People with HIV/AIDS reside in every
parish in the state, but the Baton Rouge and New
Orleans areas have very high concentrations of
cases. Metro Baton Rouge ranked 7th and New
Orleans was 9th in the nation in AIDS case rates
in 2003. AIDS Case Rate per 100,000 Population,
All Ages, Reported in 2005   LA-21 Whole
USA-14
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BC METHODS Periodic Abstinence or Fertility
Awareness Methods A woman who has a regular
menstrual cycle has about seven or more fertile
days or days when she is able to get pregnant,
each month. Periodic abstinence means you do not
have sex on the days that you may be fertile.
These fertile days are approximately 5 days
before ovulation, the day of ovulation, and one
or more days after ovulation. Fertility awareness
means that you can be abstinent or have sex but
you use a barrier method of birth control to
keep sperm from getting to the egg. Barrier
methods include condoms, diaphragms, or cervical
caps, used together with spermicides, which kill
sperm. These methods are 75 to 99 effective at
preventing pregnancy. Keep in mind that to
practice these methods, you need to learn about
your menstrual cycle (or how often you get your
period). To learn about your cycle, keep a
written record of when you get your period, what
it is like (heavy or light blood flow), and how
you feel (sore breasts, cramps). You also check
your cervical mucus and take your basal body
temperature daily, and record these in a chart.
This is how you learn to predict, or tell, which
days you are fertile or unsafe. You can ask
your doctor or nurse for more information on how
to record and understand this information.
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The Male Condom Condoms are called barrier
methods of birth control because they put up a
block, or barrier, which keeps the sperm from
reaching the egg. Only latex or polyurethane
(because some people are allergic to latex)
condoms are proven to help protect against STDs,
including HIV. "Natural or lambskin condoms
made from animal products also are available, but
lambskin condoms are not recommended for STD
prevention because they have tiny pores that may
allow for the passage of viruses like HIV,
hepatitis B and herpes. Male condoms are 84 to
98 effective at preventing pregnancy. Condoms
can only be used once. You can buy them at a drug
store. Condoms come lubricated (which can make
sexual intercourse more comfortable and
pleasurable) and non-lubricated (can also be used
for oral sex). It is best to use lubrication with
non-lubricated condoms if you use them for
vaginal or anal sex. You can use KY jelly or
water-based lubricants, which you can buy at a
drug store. Oil-based lubricants like massage
oils, baby oil, lotions, or petroleum jelly will
weaken the condom, causing it to tear or break.
Always keep condoms in a cool, dry place. If you
keep them in a hot place (like a billfold,
wallet, or glove compartment), the latex breaks
down, causing the condom to tear or break. Latex
or polyurethane condoms are the only method other
than abstinence that can help protect against HIV
and other sexually transmitted diseases (lambskin
condoms do not).
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Oral Contraceptives Also called the pill,
contains the hormones estrogen and progestin and
is available in different dosages. A pill is
taken daily to block the release of eggs from the
ovaries. Oral contraceptives lighten the flow of
your period and can reduce the risk of pelvic
inflammatory disease (PID), ovarian cancer,
benign ovarian cysts, endometrial cancer, and
iron deficiency anemia. It does not protect
against STDs or HIV. The pill may add to your
risk of heart disease, including high blood
pressure, blood clots, and blockage of the
arteries, especially if you smoke. If you are
over age 35 and smoke, or have a history of blood
clots or breast, liver, or endometrial cancer,
your doctor may advise you not to take the pill.
The pill is 95 to 99.9 effective at preventing
pregnancy. Some antibiotics may reduce the
effectiveness of the pill in some women. Talk to
your doctor or nurse about a back-up method of
birth control if she or he prescribes
antibiotics. Most oral contraceptives are
swallowed in a pill form. One brand, called Ovcon
35, can either be swallowed or chewed. If it is
chewed, you must drink a full glass of liquid
immediately after to make sure you get the full
dose of medication. There are also extended cycle
pills, brand name Seasonale, which have 12 weeks
of pills that contain hormones (active) and 1
week of pills that dont contain hormones
(inactive). While taking Seasonale, women only
have their period 4 times a year when they are
taking the inactive pills. There are many
different types of oral contraceptives available,
and it is important to talk to your doctor or
nurse about which one is best for you. You will
need a prescription for oral contraceptives.
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The Mini-Pill Unlike the pill, the mini-pill
only has one hormone, progestin, instead of both
estrogen and progestin. Taken daily, the
mini-pill thickens cervical mucus to prevent
sperm from reaching the egg. It also prevents a
fertilized egg from implanting in the uterus
(womb). The mini-pill also can decrease the flow
of your period and protect against PID and
ovarian and endometrial cancer. Mothers who
breastfeed can use it because it will not affect
their milk supply. The mini-pill is a good option
for women who cant take estrogen, are over 35,
or have a risk of blood clots. The mini-pill does
not protect against STDs or HIV. Mini-pills are
92 to 99.9 effective at preventing pregnancy if
used correctly. The mini-pill needs to be taken
at the same time each day. A back-up method of
birth control is needed if you take the pill more
than three hours late. Some antibiotics may
reduce the effectiveness of the pill in some
women. Talk to your doctor or nurse about a
back-up method of birth control if she or he
prescribes antibiotics. You will need to visit
you doctor for a prescription and to make sure
you are not having problems.
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Copper T IUD (Intrauterine Device) An IUD is a
small device that is shaped in the form of a T.
Your health care provider places it inside the
uterus. The arms of the Copper T IUD contain some
copper, which stops fertilization by preventing
sperm from making their way up through the uterus
into the fallopian tubes. If fertilization does
occur, the IUD would prevent the fertilized egg
from implanting in the lining of the uterus. The
Copper T IUD can stay in your uterus for up to 12
years. It does not protect against STDs or HIV.
This IUD is 99 effective at preventing
pregnancy. You will need to visit your doctor to
have it inserted and to make sure you are not
having any problems. Not all doctors insert IUDs
so check first before making your appointment.
Progestasert IUD (Intrauterine Device) This
IUD is a small plastic T- shaped device that is
placed inside the uterus by a doctor. It contains
the hormone progesterone, the same hormone
produced by a womans ovaries during the monthly
menstrual cycle. The progesterone causes the
cervical mucus to thicken so sperm cannot reach
the egg, and it changes the lining of the uterus
so that a fertilized egg cannot successfully
implant. The Progestasert IUD can stay in your
uterus for one year. This IUD is 98 effective at
preventing pregnancy. You will need to visit your
doctor to have it inserted and to make sure you
are not having any problems. Not all doctors
insert IUDs so check first before making your
appointment.
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Intrauterine System or IUS (Mirena) The IUS is
a small T-shaped device like the IUD and is
placed inside the uterus by a doctor. Each day,
it releases a small amount of a hormone similar
to progesterone called levonorgestrel that causes
the cervical mucus to thicken so sperm cannot
reach the egg. The IUS stays in your uterus for
up to five years. It does not protect against
STDs or HIV. The IUS is 99 effective. The Food
and Drug Administration approved this method in
December 2000. You will need to visit your doctor
to have it inserted and to make sure you are not
having any problems. Not all doctors insert the
IUS so check first before making your appointment
The Female Condom Worn by the woman, this
barrier method keeps sperm from getting into her
body. It is made of polyurethane, is packaged
with a lubricant, and may protect against STDs,
including HIV. It can be inserted up to 24 hours
prior to sexual intercourse. Female condoms are
79 to 95 effective at preventing pregnancy.
There is only one kind of female condom, called
Reality, and it can be purchased at a drug store.
40
Depo-Provera With this method women get
injections, or shots, of the hormone progestin in
the buttocks or arm every 3 months. It does not
protect against STDs or HIV. Women should not use
Depo-Provera for more than 2 years in a row
because it can cause a temporary loss of bone
density that increases the longer this method is
used. The bone does start to grow after this
method is stopped, but it may increase the risk
of fracture and osteoporosis if used for a long
time. It is 97 effective at preventing
pregnancy. You will need to visit your doctor for
the shots and to make sure you are not having any
problems.
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Diaphragm, Cervical Cap or Shield These are
barrier methods of birth control, where the sperm
are blocked from entering the cervix and reaching
the egg. The diaphragm is shaped like a shallow
latex cup. The cervical cap is a thimble-shaped
latex cup. The cervical shield is a silicone cup
that has a one-way valve that creates suction and
helps it fit against the cervix. The diaphragm
and cervical cap come in different sizes and you
need a doctor to fit you for one. The cervical
shield comes in one size and you will not need a
fitting. Before sexual intercourse, you use them
with spermicide (to block or kill sperm) and
place them up inside your vagina to cover your
cervix (the opening to your womb). You can buy
spermicide gel or foam at a drug store. Some
women can be sensitive to an ingredient called
nonoxynol-9 and need to use spermicides that do
not contain it. The diaphragm is 84 to 94
effective at preventing pregnancy. The cervical
cap is 84 to 91 effective at preventing
pregnancy for women who have not had a child and
68 to 74 for women who have had a child. The
cervical shield is 85 effective at preventing
pregnancy. Barrier methods must be left in place
for 6 to 8 hours after intercourse to prevent
pregnancy and removed by 24 hours for the
diaphragm and 48 for cap and shield. You will
need to visit your doctor for a proper fitting
for the diaphragm or cervical cap and a
prescription for the cervical shield.
42
Diaphragm, Cervical Cap or Shield These are
barrier methods of birth control, where the sperm
are blocked from entering the cervix and reaching
the egg. The diaphragm is shaped like a shallow
latex cup. The cervical cap is a thimble-shaped
latex cup. The cervical shield is a silicone cup
that has a one-way valve that creates suction and
helps it fit against the cervix. The diaphragm
and cervical cap come in different sizes and you
need a doctor to fit you for one. The cervical
shield comes in one size and you will not need a
fitting. Before sexual intercourse, you use them
with spermicide (to block or kill sperm) and
place them up inside your vagina to cover your
cervix (the opening to your womb). You can buy
spermicide gel or foam at a drug store. Some
women can be sensitive to an ingredient called
nonoxynol-9 and need to use spermicides that do
not contain it. The diaphragm is 84 to 94
effective at preventing pregnancy. The cervical
cap is 84 to 91 effective at preventing
pregnancy for women who have not had a child and
68 to 74 for women who have had a child. The
cervical shield is 85 effective at preventing
pregnancy. Barrier methods must be left in place
for 6 to 8 hours after intercourse to prevent
pregnancy and removed by 24 hours for the
diaphragm and 48 for cap and shield. You will
need to visit your doctor for a proper fitting
for the diaphragm or cervical cap and a
prescription for the cervical shield.
43
Contraceptive Sponge - This is a barrier method
of birth control that was re-approved by the Food
and Drug Administration in 2005. It is a soft,
disk shaped device, with a loop for removal. It
is made out of polyurethane foam and contains the
spermicide nonoxynol-9. Before intercourse, you
wet the sponge and place it, loop side down, up
inside your vagina to cover the cervix. The
sponge is 84 to 91 effective at preventing
pregnancy in women who have not had a child and
68 to 80 for women who have had a child. The
sponge is effective for more than one act of
intercourse for up 24 hours. It needs to be left
in for at least six hours after intercourse to
prevent pregnancy and must be removed within 30
hours after it is inserted. There is a risk of
getting Toxic Shock syndrome or TSS if the sponge
is left in for more than 30 hours. The sponge
does not protect against STDs or HIV. There is
only one kind of contraceptive sponge for sale in
the United States, called the Today Sponge, and
it can be purchased at a drug store. Women who
are sensitive to the spermicide nonoxynol-9
should not use this birth control method.
44
The Patch (Ortho Evra) This is a skin patch worn
on the lower abdomen, buttocks, or upper body. It
releases the hormones progestin and estrogen into
the bloodstream. You put on a new patch once a
week for three weeks, and then do not wear a
patch during the fourth week in order to have a
menstrual period. The patch is 98 to 99
effective at preventing pregnancy, but appears to
be less effective in women who weigh more than
198 pounds. It does not protect against STDs or
HIV. You will need to visit your doctor for a
prescription and to make sure you are not having
problems.
45
The Hormonal Vaginal Contraceptive Ring
(NuvaRing) The NuvaRing is a ring that releases
the hormones progestin and estrogen. You squeeze
the ring between your thumb and index finger and
insert it into your vagina. You wear the ring for
three weeks, take it out for the week that you
have your period, and then put in a new ring. The
ring is 98 to 99 effective at preventing
pregnancy. You will need to visit your doctor for
a prescription and to make sure you are not
having problems. This birth control method is not
recommended while breastfeeding because the
hormone estrogen may decrease breast milk
production. Surgical Sterilization (Tubal
Ligation or Vasectomy) These surgical methods
are meant for people who want a permanent method
of birth control. In other words, they never want
to have a child or they do not want more
children. Tubal ligation or tying tubes is done
on the woman to stop eggs from going down to her
uterus where they can be fertilized. The man has
a vasectomy to keep sperm from going to his
penis, so his ejaculate never has any sperm in
it. They are 99.9 effective at preventing
pregnancy.
46
Nonsurgical Sterilization (Essure Permanent Birth
Control System) This is the first non-surgical
method of sterilizing women. A thin tube is used
to thread a tiny spring-like device through the
vagina and uterus into each fallopian tube.
Flexible coils temporarily anchor it inside the
fallopian tube. A Dacron-like mesh material
embedded in the coils irritates the fallopian
tubes lining to cause scar tissue to grow and
eventually permanently plug the tubes. It can
take about three months for the scar tissue to
grow, so it is important to use another form of
birth control during this time. Then you will
have to return to your doctor for a test to see
if scar tissue has fully blocked your tubes. -
After 3 years of follow-up studies, Essure has
been shown to be 99.8 effective in preventing
pregnancy.
47
Emergency Contraception This is NOT a regular
method of birth control and should never be used
as one. Emergency contraception, or emergency
birth control, is used to keep a woman from
getting pregnant when she has had unprotected
vaginal intercourse. Unprotected can mean that
no method of birth control was used. It can also
mean that a birth control method was used but did
not work like a condom breaking. Or, a woman
may have forgotten to take her birth control
pills, or may have been abused or forced to have
sex when she did not want to. Emergency
contraception consists of taking two doses of
hormonal pills taken 12 hours apart and started
within three days after having unprotected sex.
These are sometimes wrongly called the morning
after pill. The pills are 75 to 89 effective at
preventing pregnancy. Another type of emergency
contraception is having the Copper T IUD put into
your uterus within seven days of unprotected sex.
This method is 99.9 effective at preventing
pregnancy. Neither method of emergency
contraception protects against STDs or HIV. You
will need to visit your doctor for either a
prescription for the pills or for the insertion
of the IUD, and to make sure you are not having
problems.
48
Endocrinology genetic sex established at
conception Direction of differentiation due to
hormones Gonadal sex regulates the phenotypic
sex Devt of brain dependent on hormones
present Compared to female, male devt of
reproductive system is uncomplicated. After
puberty-male is tonic Female is cyclic in
hormonal output and gonadal function Also she can
become pregnant Unique female hormones Milk
production after delivery

49
Sex Determination Genetic Sex, determine at
conception governs the development of the gonadal
sex of the individual Gonadal sex regulates
development of phenotypic sex and internal and
external sex organs as well as attainment of
adult sexual characteristics.

50
Chromosomal (genetic) basis of sex
determination No matter what chromosome is-lack
of Y-get a female Although the genetic sex of the
species determine the direction in which the
gonads initially differentiate, the exogenous
administration of sex steroids at a critical time
(varies among species) can induce permanent
gonadal sex reversal

51
Sex Chromosomes and Determination of Sex Humans
usually have 46 chromosomes per diploid cell
consisting of 22 sets of autosomes and a set of
sex chromosomes - either XX or XY. In the usual
course of events, individuals with the karyotype
46, XX are female and individuals with 46, XY,
are male. How is the sex of an individual is
determined. Is sex determined by the number of X
chromosomes - with one X you are male or with 2
X's you are female? NO Or is sex determined by
the presence or absence of the Y chromosome - the
presence of a Y makes for a male or the absence
of a Y produces a female?

52

• Sex Chromosomes and Determination of Sex
• One way the answer was provided by individuals
  resulting from non-disjunction of the sex
  chromosomes. Some individuals have 45 chromosomes
  and have only one X chromosome other individuals
  have 47 chromosomes and have two X chromosomes
  and a Y. The table below indicates the sex of
  these individuals.
• ChromosomeConstitution Name of Syndrome
  Sex Frequency in Population
• 46, XX
  Normal Female 0.511
• 46, XY
  Normal Male 0.489
• 45, XO Turner's Syndrome
  Female 1/5,000
• XXY Klinefelter's Syndrome
  Male 1/700Female
• (46,XX) and Male (46,XY) frequencies taken from
  the US Census projection of July 1, 1996 with no
  correction for chromosome constitution.
• It is clear that the presence of a Y chromosome
  is necessary for male sexual characteristics to
  develop. The number of X chromosomes present does
  not play a significant role in sex determination.
  

53
SRY Sex determination We have come a long way
in our understanding of sexual dimorphism since
355 BC. In those days, Aristotle suggested that
the difference between the two sexes was due to
the heat of semen at the time of copulation hot
semen generated males, whereas cold semen made
females. Thankfully, we now know a little more
about the molecular events of sex determination.
Usually, a woman has two X chromosomes (XX) and
a man one X and one Y (XY). However, both male
and female characteristics can sometimes be found
in one individual, and it is possible to have XY
women and XX men. Analysis of such individuals
has revealed some of the molecules involved in
sex determination, including one called SRY,
which is important for testis formation.
54
SRY Sex determination SRY (which stands for
sex-determining region Y gene) is found on the Y
chromosome. In the cell, it binds to other DNA
and in doing so distorts it dramatically out of
shape. This alters the properties of the DNA and
likely alters the expression of a number of
genes, leading to testis formation. Most XX men
who lack a Y chromosome do still have a copy of
the SRY region on one of their X chromosomes.
This copy accounts for their maleness. However,
because the remainder of the Y chromosome is
missing they frequently do not develop secondary
sexual characteristics in the usual way. Since
human SRY is similar to SRY of mice, a model of
SRY function has been developed in mice. This has
been particularly important in discovering the
interactions of SRY with other genes in male sex
determination.

55
Mammalian testicular organogenesis dependent on
protein TDF or SRY Female mice embryos with
normal pair of XX Are injected with a small piece
of Y containing SRY, they grow up as males with
testis and male behavior Y triggers the genital
ridges in embryo to develop into testes rather
than ovaries Once that happens, all other changes
that make a male follow under the influence of
hormones produced by the testes SRY gene is only
a SWITCH

56

SRY is only a switch because testes can develop
in XX women who have no portion of the Y In
cattle, some genetic females have testes So,
genes found in females
57

Gonadal Steroid and Brain Differentiation Expts
have shown that transplantation of the pit from a
male to a female rat to the opposite sex did not
alter the normal reproductive processes in either
sex. Pits are equivalent We know tonic in males
and cyclic in females
58
Neonatal male develop into adult male with male
behavior But if castrate at critical period
becomes a feminized male with female
behavior Neonate female develops into adult
female with female behavior But if put in
testosterone at critical period then get
masuclinized female with male behavior

59

These results suggest that control of pit hormone
secretion and subsequent gonadal function depend
on a system that is programmed early in
development was not localized to the pit or the
gonads.
60
Steroid hormones derived from Cholesterol Andros
tenedione (testis) Testosterone
Estradiol
5a reductase
DHT

61
A single treatment of a chick embryos with an
aromatase inhibitor at a stage when gonads are
bipotential causes genetic females to
permanently develop a male phenotype Aromatase
is key developmental switch in the sex
determination of chickens

62
Many breast tumors are highly "estrogen
sensitive," so estrogen stimulates their
growth Aromatase inhibitors (AIs) can help block
the growth of these tumors by lowering the amount
of E in the body. Estrogen is produced by the
ovaries and other tissues of the body, via
aromatase. AIs do not block estrogen production
by the ovaries, but they can block other tissues
from making this hormone. That's why AIs are used
mostly in women who have reached menopause, when
the ovaries are no longer producing
estrogen. Currently , there are several AIs
approved by the U.S. Food and Drug
Administration anastrazole (Arimidex),
exemestane (Aromasin), and letrozole (Femara).


63
Males The principal androgen (male sex hormone)
is testosterone. This steroid is manufactured by
the interstitial (Leydig) cells of the testes.
Secretion of testosterone increases sharply at
puberty and is responsible for the development of
the so-called secondary sexual characteristics
(e.g., beard) of men. Testosterone is also
essential for the production of sperm.
Production of testosterone is controlled by the
release of LH from the anterior lobe of the
pituitary gland, which is in turn controlled by
the release of GnRH from the hypothalamus. LH is
also called interstitial cell stimulating hormone
(ICSH).

64
Males Hypothalamus?GnRH? Pituitary?LH?Testes?Te
stosterone The level of testosterone is under
negative-feedback control a rising level of
testosterone suppresses the release of GnRH from
the hypothalamus. This is exactly parallel to the
control of estrogen secretion in females.

65
Males Males need estrogen, too! In 1994, a man
was described who was homozygous for a mutation
in the gene encoding the estrogen receptor. A
single nonsense mutation had converted a codon
(CGA) for arginine early in the protein into a
STOP codon (TGA). Thus no complete ER could be
synthesized. This man was extra tall, had
osteoporosis and "knock-knees", but was otherwise
well. His genetic defect confirms the important
role that estrogen has in both sexes for normal
bone development.

66
Males It is not known whether this man (or any
of the few other men who have been found with the
same disorder) is fertile or not. However, an
article in the 4 December 1997 issue of Nature
reports that male mice whose ER gene has been
"knocked out" are sterile.

67
Males Anabolic steroids A number of synthetic
androgens are used for therapeutic purposes.
These drugs promote an increase in muscle size
with resulting increases in strength and speed.
This has made them popular with some athletes
(weight lifters, cyclists, runners, swimmers,
professional football players). Usually these
athletes (females as well as males) take doses
far greater than those used in standard therapy.
Such illicit use carries dangers (besides being
banned from an event because of a positive drug
test) acne, a decrease in libido, and in males
testicle size and sperm counts to name a few.

68
Males Genetic abnormalities of gonadal
function. Many things can go wrong with sexual
development in both males and females
fortunately rarely. only a few that clearly
result from the inheritance of single-gene
mutations. Inherited mutations in both copies of
the gene encoding the GnRH receptor result in
failure to develop at puberty. Mutations in the
gene encoding the LH receptor prevent normal
sexual development in both sexes.

69
Males Genetic abnormalities of gonadal
function. Mutations in the gene encoding the FSH
receptor block development of the gonads in both
males and females. Mutations in any of the genes
encoding the enzymes for synthesis and metabolism
of testosterone interfere with normal sexual
function in males. A similar spectrum of
disorders in males can be caused by mutations in
the genes encoding the androgen receptor.

70
Females The ovaries of sexually-mature females
secrete a mixture of estrogens of which
17ß-estradiol is the most abundant (and most
potent) and progesterone.

71
Females Estrogens Estrogens are steroids.
primarily responsible for the conversion of
girls into sexually-mature women. development of
breasts further development of the uterus and
vagina broadening of the pelvis growth of pubic
and axillary hair increase in adipose (fat)
tissue participate in the monthly preparation of
the body for a possible pregnancy participate in
pregnancy if it occurs

72
Females Estrogens also have non-reproductive
effects. They antagonize the effects of the
parathyroid hormone, minimizing the loss of
calcium from bones and thus helping to keep bones
strong. They promote blood clotting.

73
Females Progesterone Progesterone is also a
steroid. It has many effects in the body, some
having nothing to do with sex and reproduction.
See Monday notes for the role and regulation of
progesterone in the menstrual cycle and pregnancy

74
How estrogens and progesterone achieve their
effects Steroids like estrogens and progesterone
are small, hydrophobic molecules that are
transported in the blood bound to a serum
globulin. In "target" cells, i.e., cells that
change their gene expression in response to the
hormone, they bind to receptor proteins located
in the cytoplasm and/or nucleus. The
hormone-receptor complex enters the nucleus (if
it formed in the cytoplasm) and binds to
specific sequences of DNA, called the estrogen
(or progesterone) response elements

75
How estrogens and progesterone achieve their
effects Response elements are located in the
promoters of genes. The hormone-receptor complex
acts as a transcription factor (often recruiting
other transcription factors to help) which turns
on (sometimes off) transcription of those genes.
Gene expression in the cell produces the
response.

76
Regulation of Estrogen and Progesterone The
synthesis and secretion of estrogens is
stimulated by follicle-stimulating hormone (FSH),
which is, in turn, controlled by the hypothalamic
gonadotropin releasing hormone (GnRH).
Hypothalamus?GnRH? Pituitary?FSH?Follicle?Estroge
ns

77
Hermaphroditism is a term referring to being of
both sexes (intersexual). True hermaphroditism
requires the presence of both ovarian (female)
and testicular (male) reproductive tissue and is
relatively rare and poorly understood.
Pseudo-hermaphroditism is more common. From a
medical standpoint, hermaphroditism suggests two
factors ambiguous external genitalia genitalia
that do not match the genetic make-up of the
person (example female genitalia in a
genetically male individual)

78
The following conditions can produce ambiguous
genitalia and hermaphroditism congenital
adrenal hyperplasia fetal exposure to sex
hormones testicular feminization syndrome XY
gonadal dysgenesis XY gonadal agenesis
(testicular regression syndrome is very rare
disease) chromosomal abnormalities

79
Congenital adrenal hyperplasia refers to a group
of inherited disorders relating to the adrenal
glands, characterized by a deficiency in the
hormones cortisol and aldosterone and an
overproduction of androgen. Alternative Names
Adrenogenital syndrome 21-hydroxylase deficiency


80
Congenital adrenal hyperplasia Causes,
incidence, and risk factors The different types
of adrenogenital syndrome are inherited as
autosomal recessive diseases and can affect both
boys and girls. The defect is lack of an enzyme
needed by the adrenal gland to make the major
steroid hormones of the adrenal cortex cortisol
and aldosterone. Due to the block in synthesis of
these hormones, there is abnormal 'feedback' and
steroids are 'diverted' to becoming androgens, a
form of male sex hormones.

81
Congenital adrenal hyperplasia This causes
early appearance of male characteristics. In a
newborn girl with this disorder, the clitoris is
enlarged with the urethral opening at the base
(ambiguous genitalia, often appearing more
male-like than female). The internal structures
of the reproductive tract (ovaries, uterus, and
fallopian tubes) are normal. As she grows older,
masculinization of some features takes place,
such as deepening of the voice, the appearance of
facial hair, and failure to menstruate at
puberty. In a newborn boy no obvious abnormality
is present, but long before puberty normally
occurs, the child becomes increasingly muscular,
the penis enlarges, pubic hair appears, and the
voice deepens. Affected males may appear to enter
puberty as early as 2-3 years of age. At
puberty, the testes are small.

82
Congenital adrenal hyperplasia Some forms of
congenital adrenal hyperplasia are more severe
and cause adrenal crisis in the newborn due to
salt wasting. In this salt-losing form of
congenital adrenal hyperplasia, newborns develop
symptoms shortly after birth. These include
vomiting, dehydration, electrolyte changes, and
cardiac arrhythmias. Untreated, this condition
can lead to death within 1-6 weeks after
birth. About 1 in 10,000 to 18,000 children are
born with congenital adrenal hyperplasia.

83
Turner syndrome A disorder in women caused by a
chromosomal defect. This disorder inhibits sexual
development and causes infertility. Alternative
NamesBonnevie-Ullrich syndrome Gonadal
dysgenesis Monosomy X Causes, incidence, and
risk factorsTurner syndrome is usually caused by
a missing X chromosome. It affects 1 out of 3,000
live births. It is usually sporadic meaning that
it is not inherited from a parent.
84
Turner syndrome Rarely, a parent silently
carries rearranged chromosomes that can result in
Turner syndrome in a daughter this is the only
situation in which Turner syndrome is inherited.
There are many manifestations of this syndrome,
but the main features are short stature, webbing
of the skin of the neck, absent or retarded
development of secondary sexual characteristics,
absence of menstruation, coarctation (narrowing)
of the aorta, and abnormalities of the eyes and
bones. The condition is either diagnosed at
birth because of the associated anomalies, or at
puberty when there is absent or delayed menses
and delayed development of normal secondary
sexual characteristics.
85
Ambiguous genitalia A congenital physical
abnormality where the outer genitals do not have
the typical appearance of either sex.
ConsiderationsThe genetic sex of a child is
determined at conception. The egg cell (ovum)
contains a chromosome called the X chromosome.
Sperm cells contain either an X chromosome or one
called the Y chromosome. These determine the
child's genetic sex. Normally an infant will
inherit ONE PAIR (one from the mother and one
from the father) of these "sex chromosomes" (two
chromosomes).

86
Ambiguous genitalia Thus, it is the father who
"determines" the genetic sex of the child. An
infant who inherits the X chromosome from the
father is a genetic female (XX pattern) and one
who inherits the Y chromosome is a genetic male
(XY pattern).The reproductive organs and
genitals associated with "female" or "male" arise
from the same initial (fetal) tissue. If the
process that causes this fetal tissue to become
"male" or "female" is disrupted, ambiguous
genitalia can develop.

87
Ambiguous genitalia Ambiguous genitalia are
those in which it is difficult to classify the
infant (by physical examination) as male or
female. The extent of the ambiguity varies. In
very rare instances, the physical appearance may
be fully developed as the opposite of the genetic
sex (e.g., a genetic male may have normal female
appearance).Typical ambiguous genitalia in
genetic females include an enlarged clitoris that
has the appearance of a small penis. The urethral
opening (where urine comes out) can be anywhere
along, above, or below the surface of the
clitoris, which may be considered normal or
common abnormalities of anatomic urethra
placement (such as hypospadias, when the urethra
is on the underside of the penis, instead of at
the tip).

88
Ambiguous genitalia The labia may be fused,
resembling a scrotum. The infant may be thought
to be a male with undescended testicles
sometimes a lump of tissue is felt within the
fused labia, further making it look like a
scrotum with testicles.

89
Ambiguous genitalia In a genetic male, findings
of ambiguous genitalia include a small penis,
less than 2 to 3 centimeters (0.8 to 1.2 inches)
that may appear to be an enlarged clitoris (the
clitoris of a newborn female is normally somewhat
enlarged at birth). The urethral opening may be
anywhere along, above, or below the penis it can
be placed as low as on the peritoneum, further
making the infant appear to be a female. There
may be a small scrotum with any degree of
separation, resembling labia. Undescended
testicles commonly accompany ambiguous
genitalia.Uncertain or mistaken sex is not a
physical threat to life, but can create social
upheaval for the child and the family.

90
Ambiguous genitalia Common Causes pseudohermap
hroditism (when the genitalia are of one sex, but
some physical characteristics of the other sex
are present) true hermaphrodism (very rare --
both ovarian and testicular tissue is present and
the child may have parts of both male and female
genitalia) mixed gonadal dysgenesis (where some
cells in the body have only a single X
chromosome--female, and some cells in the body
have XY chromosomes--male. This syndrome is
variable, and depends on which cells are female,
which cells are male, and what percent of each
there are

91
Ambiguous genitalia Common Causes congenital
adrenal hyperplasia (several forms, but the most
common form causes the genetic female to appear
male. Male infants with the most common form
appear normal at birth, but may show premature
sexual development as early as 6 months of age)
-- many states test for this as part of the
newborn screen (the blood test a baby has at
24-48 hours of life) To look for chromosomal
abnormalities

92
Ambiguous genitalia Common Causes Klinefelter'
s syndrome (XXY--male, usually has small testes
causes infertility may be associated with
learning defects or mental retardation affects
1/500-1/1000 live male births) Turner's syndrome
(XO--female usually does not cause ambiguous
genitalia (usually looks female at birth), but
may have webbed neck, swelling of the hands and
feet and other characteristic physical findings
at birth may not be diagnosed until later in
life when sexual maturation does not take place
infertile)

93
Ambiguous genitalia Common Causes maternal
ingestion of certain medications (particularly
androgenic steroids) -- may make a genetic female
look more male lack of production of specific
hormones, causing the embryo to develop with a
female body type regardless of genetic sex lack
of testosterone cellular receptors (so even if
the body makes the hormones needed to develop
into a physical male, the body is unable to
respond to those hormones, and therefore, a
female body-type is the result even if the
genetic sex is male)

94
Puberty-Time to Change When your body reaches a
certain age, your brain releases GnRH that starts
the changes of puberty. When GnRH reaches the
pituitary gland, this gland releases into the
bloodstream two more puberty hormones LH and
FSH. Guys and girls have both of these hormones
in their bodies. And depending on whether you're
a guy or a girl, these hormones go to work on
different parts of the body.

95
Puberty Guys- these hormones travel through the
blood and give the testes the signal to begin the
production of testosterone and sperm.
Testosterone is the hormone that causes most of
the changes in a guy's body during puberty. Sperm
cells must be produced for men to reproduce. In
girls, FSH and LH target the ovaries, which
contain eggs that have been there since birth.
The hormones stimulate the ovaries to begin
producing another hormone called estrogen.
Estrogen, along with FSH and LH, causes a girl's
body to mature and prepares her for pregnancy.

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