Transcript Slide 1

John Rock’s 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
-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, don’t you sell my church short.”
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 couldn’t 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
Pregnant women make progestin so egg can’t 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
Pill’s ingredients duplicated what can be found in the body, had
theological significance to ROCK.
1951 – Pope Pius XII sanctioned rhythm method – deemed it natural
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…..
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
Pill – no egg released
Flux of hormones cause lining to grow are dramatically reduced
Effect of Pill’s 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
That was his error; Not so natural after all
________________________________________________________
1986 Bev Strassman (U Mich) – Africa Dogon tribe in Mali.
Use no contraception.
Wanted 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)
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
Number of lifetime menses isn’t 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 women’s health?
Doesn’t 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
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%
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 A&M, women stay on Pill 6-12 weeks before spotting
During placebo week, a number of pill users have pelvic pain, bloating,
swelling, headaches, etc…Side effects of normal menstruation
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 30’s & 40’s & < with
menopause
So if toxin – expect increase each year
Also, women had ovaries removed had less cancer
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)
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
Explains 25% difference
US = 145
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 wasn’t solution: was hormone that caused cell%
Pill has no effect on BC
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
Conventional Pill → Little Pregnancy
Pike’s 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
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
1963 – (after Rock’s 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.
Sad ending
Rock didn’t live to see Pill’s effect on cancer rates
Saw (at end of 60’s) Pill wrongly accused of causing blood clots,
strokes, heart attacks
Mid 70’s-Early 80’s
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”
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 UNCChapel 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.
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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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.
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.
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.
Estrogen in the body cause the pituitary gland to release
LH stimulating the ovary to produce a ripe egg.
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.
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.
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
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
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.
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).
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 don’t 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.
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 can’t 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.
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 woman’s 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.
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.
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.
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 oneway 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.
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 oneway 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.
Contraceptive Sponge - This is a barrier method of birth control that was reapproved 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.
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.
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.
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.
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.
» The Menstrual Cycle
» About every 28 days, some blood and other products
of the disintegration of the inner lining of the uterus
(the endometrium) are discharged from the uterus, a
process called menstruation. During this time a new
follicle begins to develop in one of the ovaries. After
menstruation ceases, the follicle continues to develop,
secreting an increasing amount of estrogen as it does
so.
» The rising level of estrogen causes the endometrium to
become thicker and more richly supplied with blood
vessels and glands.
» A rising level of LH causes the developing egg within
the follicle to complete the first meiotic division
(meiosis I), forming a secondary oocyte.
» After about two weeks, there is a sudden surge in the
production of LH.
» This surge in LH triggers ovulation: the release of the
secondary oocyte into the fallopian tube.
– Under the continued influence of LH, the now-empty
follicle develops into a corpus luteum (hence the name
luteinizing hormone for LH).
– Stimulated by LH, the corpus luteum secretes
progesterone which
• continues the preparation of the endometrium for a
possible pregnancy
• inhibits the contraction of the uterus
• inhibits the development of a new follicle
– If fertilization does not occur (usually the case),
• the rising level of progesterone inhibits the release
of GnRH which, in turn,
• inhibits further production of progesterone.
– As the progesterone level drops,
• the corpus luteum begins to degenerate;
• the endometrium begins to break down, its cells
committing programmed cell death (apoptosis);
• the inhibition of uterine contraction is lifted, and
• the bleeding and cramps of menstruation begin.
• Pregnancy
• Fertilization of the egg takes place within
the fallopian tube. As the fertilized egg
passes down the tube, it undergoes its first
mitotic divisions. By the end of the week,
the developing embryo has become a
hollow ball of cells called a blastocyst. At
this time, the blastocyst reaches the uterus
and embeds itself in the endometrium, a
process called implantation. With
implantation, pregnancy is established.
•
Pregnancy
• The blastocyst has two parts:
• the inner cell mass, which will become the
baby, and
• the trophoblast, which will
– develop into the extraembryonic membranes,
the
• amnion
• placenta, and
• umbilical cord
– and begin to secrete human chorionic
gonadotropin (HCG).
Pregnancy
• HCG is a glycoprotein. It is a dimer of the
same a subunit (89 aa) used by TSH, FSH,
and LH) and unique b subunit (148 aa).
• HCG behaves much like FSH and LH with
one crucial exception: it is NOT inhibited by
a rising level of progesterone.
• Thus HCG prevents the deterioration of the
corpus luteum at the end of the fourth week
and enables pregnancy to continue beyond
the end of the normal menstrual cycle.
Pregnancy
Because only the implanted trophoblast makes HCG, its early
appearance in the urine of pregnant women provides the
basis for the most widely used test for pregnancy (which can
provide a positive signal even before menstruation would
have otherwise begun).
» As pregnancy continues, the placenta becomes a major
source of progesterone, and its presence is essential to
maintain pregnancy. Mothers at risk of giving birth too soon
can be given a synthetic progestin to help them retain the
fetus until it is full-term.
Birth
• Toward the end of pregnancy,
• Secretion of estrogen by the placenta rises.
– This rise is triggered by the fetus itself: The placenta
releases CRH which stimulates the pituitary of the fetus to
secrete ACTH, which acts on the adrenal glands of the fetus
causing them to release the estrogen precursor
dehydroepiandrosterone sulfate (DHEA-S).
This is converted into estrogen by the
placenta.
Birth
• The rising level of estrogen causes the smooth
muscle cells of the uterus to
– synthesize connexins and form gap junctions.
Gap junctions connect the cells electrically so
that they contract together as labor begins.
– express receptors for oxytocin
• Oxytocin is secreted by the posterior lobe of the
pituitary as well as by the uterus.
• A number of prostaglandins also appear in the
mother's blood as well as in the amniotic fluid.
• Both oxytocin and prostaglandins cause the
uterus to contract and labor begins.
•
•
•
•
Birth
Three or four days after the baby is born,
the breasts begin to secrete milk.
Milk synthesis is stimulated by the pituitary
hormone prolactin (PRL), and
its release from the breast is stimulated by
oxytocin.
Milk contains an inhibitory peptide. If the
breasts are not fully emptied, the peptide
accumulates and inhibits milk production.
This autocrine action thus matches supply
with demand.
Birth-Other Hormones
• Relaxin-As the time of birth approaches in
some animals (e.g., pigs, rats) , this
polypeptide has been found to:
– relax the pubic ligaments
– soften and enlarge the opening to the cervix.
• Relaxin is found in pregnant humans but at higher
levels early in pregnancy than close to the time of
birth. Relaxin promotes angiogenesis, and in
humans it probably plays a more important role in
the development of the interface between the
uterus and the placenta that it does in the birth
process.
Birth
Activins, Inhibins, Follistatin.
• These proteins are synthesized within the
follicle. Activins and inhibins bind to
follistatin. Activins increase the action of
FSH; inhibins, as their name suggests,
inhibit it. How important they are in humans
remains to be seen. However the important
role that activin and follistatin play in the
embryonic development of vertebrates
justifies mentioning them
Oral contraceptives: the "pill"
• The feedback inhibition of GnRH secretion
by estrogens and progesterone provides the
basis for the most widely-used form of
contraception. Dozens of different
formulations of synthetic estrogens or
progestins (progesterone relatives) — or
both — are available. Their inhibition of
GnRH prevents the mid-cycle surge of LH
and ovulation. Hence there is no egg to be
fertilized.
Oral contraceptives: the "pill"
• Usually the preparation is taken for about
three weeks and then stopped long enough
for normal menstruation to occur.
• The main side-effects of the pill stem from
an increased tendency for blood clots to
form (estrogen enhances clotting of the
blood).
RU-486
• RU-486 (also known as mifepristone) is a
synthetic steroid related to progesterone.
Unlike the synthetic progestins used in oral
contraceptives that mimic the actions of
progesterone, RU-486 is a progesterone
antagonist; that is, it blocks the action of
progesterone. It does this by binding more
tightly to the progesterone receptor than
progesterone itself but without the normal
biological effects:
•
•
•
•
•
•
RU-486
The RU-486/receptor complex is not active
as a transcription factor.
Thus genes that are turned on by
progesterone are turned off by RU-486.
The proteins needed to establish and
maintain pregnancy are no longer
synthesized.
The endometrium breaks down.
The embryo detaches from it and can no
longer make chorionic gonadotropin (HCG).
Consequently the corpus luteum ceases its
RU-486
• The inhibition on uterine contraction is
lifted.
• Soon the embryo and the breakdown
products of the endometrium are expelled.
• These properties of RU-486 have caused it
to be used to induce abortion of an
unwanted fetus. In practice, the physician
assists the process by giving a synthetic
prostaglandin (e.g., misoprostol [Cytotec®])
36–48 hours after giving the dose of RU-486.
Use of RU-486 is generally limited to the first
seven weeks of pregnancy.
RU-486
• RU-486 has been used for many years in
some countries. However, the controversies
surrounding abortion in the United States
kept it from being authorized for use here
until September 2000.
Menopause
• Menstrual cycle continues for many years. But
eventually, usually between 42 and 52 years of
age, the follicles become less responsive to FSH
and LH. They begin to secrete less estrogen.
Ovulation and menstruation become irregular and
finally cease. This cessation is called menopause.
• With levels of estrogen now running one-tenth or
less of what they had been, the hypothalamus is
released from their inhibitory influence (bar). As a
result it now stimulates the pituitary to increased
activity. The concentrations of FSH and LH in the
blood rise to ten or more times their former
values. These elevated levels may cause a variety
of unpleasant physical and emotional symptoms.
Hormone replacement therapy (HRT)
Many menopausal women elect to take a combination of E
and P after they cease to make their own. The benefits are:
• reduction in the unpleasant symptoms of the menopause
• a reduction in the loss of calcium from bones and thus a
reduction in osteoporosis and the fractures that
accompany it.
• It was also believed that HRT reduced the risk of
cardiovascular disease. However, a recent study of 16,000
menopausal women was stopped 3 years early when it was
found that, in fact, HRT increased (albeit only slightly) not
decreased the incidence of cardiovascular disease.
• Perhaps synthetic selective estrogen response modulators
or SERMs (raloxifene is an example) will provide the
protective effects without the harmful ones. Stay tuned.
Environmental estrogens
Some substances that find their way into the
environment, such as
• DDE, a breakdown product of the once widelyused insecticide DDT,
• DDT itself (still used in some countries (e.g.,
Mexico), and
• PCBs, chemicals once used in a wide variety of
industrial applications
can bind to the estrogen (and androgen) receptors
and mimic (weakly) the effects of the hormone.
This has created anxiety that they may be
responsible for harmful effects such as cancer
and low sperm counts.
Environmental estrogens
• However, there is as yet little evidence to support
these worries.
• No epidemiological relationship has been found
between the incidence of breast cancer and the
levels of these compounds in the body.
• As for laboratory studies that found a synergistic
effect of two of these substances on receptor
binding (findings that created the great alarm),
these have not been replicated in other
laboratories, and the authors of the original report
have since withdrawn it as invalid.
2002 July 10th (WHI) clinical trial tracked the
long term effects of hormone (HT) trial was
being halted three years ahead of schedule.
The results showed an unacceptable proportion
of women were harmed by the therapy. Data
implied that HT did not protect against memory
loss and other neurodegenerative conditions
such as dementia, and in fact increased their
risk of stroke and breast cancer.
At the time, some 14 million US women were
taking HT to relieve postmenopausal
symptoms or to lower their risk for
osteoporosis.
Numerous studies had suggested that hormone
treatment, using synthetic estrogens or a
combination of synthetic estrogens and
progestins, protected women from many
diseases, whereas the absence of estrogen
made women more vulnerable.
WHI -20,000 participants, was the largest clinical
trial to date. With numbers like that it was very
difficult to argue that estrogen wasn’t harmful.
Was cause to argue estradiol, was protective
against damage caused by stroke.
Would estradiol influence the extent of injury in
rats after we experimentally induced
cerebrovascular stroke by blocking blood flow to
a major vessel in the brain.
Animals with very low levels of estradiol
experienced approximately half the amount
of injury compared to animals without
estrogens.
Estradiol had to be present before we
performed the stroke injury; otherwise
treatment was totally ineffective in
protecting the brain.
Low doses were as effective as higher
doses.
Experiment was performed in mice, direct
opposition to the WHI findings.
Estrogens - pleiotropic hormone
which actd on a plethora of
physiological functions not directly
related to reproduction, therefore also
important in male physiology.
Estrogens were important players in
the immune system, in cardiovascular
function, in bone formation and
breakdown, in fat distribution and
metabolism, learning and memory.
Community of estrogen researchers
rallied together
Why the discrepancies between this
major clinical trial and previous
studies.
Estrogens influenced many genes that
regulate cell survival and cell death.
Low concentrations of estradiol
protected the brain by suppressing
apoptosis.
Estradiol could change the expression of
multiple genes and proteins.
Estradiol helps maintain levels of bcl-2, a
protein which reduces apoptosis after stroke.
Estradiol inhibits caspases, proteins that
mediate cell death.
Stroke increased the expression of estrogen
receptors to allow estrogen to protect the brain
and enhance its repair. All of these changes tip
the balance toward cell survival and against cell
death.
WHI study had traced women before stroke had
occurred to capture their risk, but didn’t follow women
after their stroke to see if women taking estrogen had
improved recoveries as models suggested.
Men also produce estrogen and are protected after stroke
when estrogens are present. Not possible to treat men
with estrogen because the hormone has feminizing
effects that are not acceptable.
Development of compounds that use the same protective
mechanisms, but do not have the other effects of
estrogen.
Cytosolic estrogen receptor discovered in the
1960’s act by transporting estrogens attached
to the receptor to the nucleus where the
hormone-receptor complex bound to DNA
and acted as a transcription factor.
30 years estrogens were thought to act: via a
single receptor that acted by binding to the
promoter region
In 1996 actually two different estrogen
receptor subtypes: ERa and ERb
ERa- or ERb-knock out mice and found that
ERa plays a pivotal role in protecting the
brain against cell death.
ERb proved not to play a role in protection.
Develop drugs that target a specific receptor
to allow better outcomes from stroke.
Studies mean in terms of the results of the
WHI? Two aspects of the clinical study
design are worth considering. First, only
synthetic hormones were used. Might
account for differential actions of these
substances compared to endogenous
hormones.
Second, the average age of women
when they started the WHI trial was
63 years old and most of them had
not had hormone therapy previous to
the trial.
Most of them had been estrogen
deficient for about 12 years.
Investigate what delayed the time of
hormone treatment in mice to match that
of the WHI.
Did not treat mice immediately after
‘menopause,’ but waited for several
weeks (the equivalent of several human
years), that hormone treatment was
totally ineffective.
Estradiol acts is by suppressing inflammation,
thereby preventing cell death.
Waited a few weeks unable to suppress
inflammation.
Depends upon the presence of ERa
The timing or treatment is a critical factor to
consider.
Different kinds of estrogens and
different concentrations of hormone
have different effects.
Hormonal milieu makes a big different
in how estrogens act
Completely opposite effects depending
upon what other hormones are present
and whether they have been there before
or after estrogen exposure.
Neurogenesis dogma had been that all
neurons were born during embryonic and
early postnatal development
New neurons were born even in adulthood.
Estrogen was important in the developing
brain of an embryo. Fetal and early postnatal
brain, estrogens are factors that mediate
Neurogenesis, synapse formation and glial
differentiation
Estrogens are potent neurogenic
factors after stroke injury in the
adult brain. Effect depends on both
ERa and ERb.
Uncertain how estradiol works to
enhance Neurogenesis.
Promise for the use of estrogens in
the long-term repair and recovery
of brain function
Clinical trials such as the WHI are
impressive for the number of women they
study. But because of prohibitive costs of
performing such a large clinical trial, only a
limited number of questions can be
addressed.
In the year following WHI trail 40% of
women stopped taking hormone
replacement therapy
Realized that results should have been
interpreted with more caution.
Functions depend upon dose,
preparation, method of administration,
the recipient’s age, genetics and previous
exposure to the hormone.
Estrogens should be expected to be among the
most complex ones to understand: they exhibit a
diurnal rhythm, a monthly rhythm that is
determined by the menstrual cycle, and they act
differently depending upon whether other
reproductive hormones are present in high or low
concentrations.
Estrogens are not the panacea people thought they
were, but neither are they always harmful.