Diseases of the Female Genital Tract
Item-20, 21
Dr. A K M Maruf Raza
Professor of Pathology
JIMC
ORCID ID: https://orcid.org/0000-0003-0251-4518
Publons / Web of Science Researcher ID: P-2736-2019
Researchgate: Maruf Raza (researchgate.net)
Item No. 20
Diseases of the Cervix
Diseases of the Ovary
Diseases of the Cervix
i. Inflammation of the Cervix.
ii. Cervical polyp (Endocervical polyp).
iii. Premalignant and Malignant neoplasm of
cervix.
Acute and chronic cervicitis
• Inflammation of the cervix is called cervicitis.
• Some degree of cervical inflammation may be
found in virtually all women and it is usually of
little clinical consequence.
• Infections by E. coli, gonococci, chlamydiae,
mycoplasmas and HSV may produce
significant acute or chronic cervicitis.
Defensive mechanism against infection
• Normal vaginal and cervical mucosa has large
number of lactobacilli.
• Lactobacilli produce lactic acid, maintaining
vaginal pH below 4.5, suppressing the growth
of organisms.
• Lactobacilli at lower pH produce bacteriotoxic
hydrogen peroxide (H2O2) which kills
pathogenic organism.
Breach of defense causing infection
• Menstrual bleeding, sexual intercourse, vaginal
douching causes decrease H2O2 production by
lactobacilli, permitting the overgrowth of
microorganisms.
• Antibiotic therapy suppress lactobacilli.
• The altered vaginal and cervical environment
promotes the overgrowth of the microorganism
causing cervicitis.
Endocervical Polyp
• Endocervical polyps are common benign polyp
that arise within the endocervical canal that
may protrude through the cervical os.
• They may be the source of irregular vaginal
spotting or bleeding causing suspicion of an
ominous lesion.
Premalignant and Malignant
Neoplasm
• Worldwide, cervical carcinoma is the third most
common cancer in women.
• The Pap test/ cervical smear test and visual
examination (colposcopy test, VIA test) of cervix
helped in lowering the number of malignant ceses.
• Also the slow progression from precursor lesions
to invasive carcinoma provides ample time for
screening, detection, and preventive treatment.
Premalignant and Malignant Neoplasm
• Premalignant condition:
Cervical intraepithelial neoplasia (CIN)
• Malignant tumour:
i. Carcinoma in Situ (CIS)
ii. Squamous cell carcinoma
iii. Adenocarcinoma
iv. Adenosquamous carcinoma
v. Neuroendocrine carcinoma
Role of HPV in cervical cancer
• HPV infections in female genital tract are
extremely common; most of which are
asymptomatic.
• Most HPV infections are transient and are
eliminated by the immune response in the
course of months.
• HPVs infect immature basal cells of the
squamous epithelium in areas of epithelial
breaks or at the squamocolumnar junction.
Role of HPV in cervical cancer
• High risk HPV (HPV strain 16,18, 31, 33, 45) are
considered the single most important factor in
cervical carcinoma.
• High risk HPVs also causes squamous cell
carcinomas of vagina, vulva, tonsil and other
oropharyngeal locations.
• Low risk HPVs (HPV 6 and11) are the cause of
vulvar, perineal and perianal warts.
Role of HPV in cervical cancer
• The high risk HPV (HPV 16,18, 31, 33, 45) acts
as a carcinogic agent in cervical carcinoma.
• The ability of HPV to act as a carcinogen
depends on the HPV viral proteins E6 and E7.
• Viral E7 protein binds the active form of tumor
suppressor RB gene and causes its
degradation.
Role of HPV in cervical cancer
• Viral proteins E6 and E7 inhibits p21 and p27,
two important cell cycle inhibitors.
• Inhibiting tumor suppressor gene and cell
cycle inhibitors enhances cell cycle
progression of mutated cervical epithelial cells.
• And also impairs the ability of cells to repair
DNA damage.
The risk factors for cervical cancer
1. Persistent infection with a high oncogenic
risk HPV, HPV 16 or HPV18
2. Multiple sexual partners.
3. Young age at first intercourse.
4. High parity.
5. Immunosuppression.
6. Use of oral contraceptives.
7. Use of nicotine (cigarette, tobacco).
Cervical intraepithelial neoplasia (CIN)
• Cervical intraepithelial neoplasia (CIN) is a
precancerous condition of the cervix.
• CIN may exist in the noninvasive stage for as
long as 20 years.
• And shed abnormal cells that can be detected
on cytologic (Paps test) examination.
Cervical intraepithelial neoplasia (CIN)
Classified in a variety of ways :
• Mild, moderate and severe dysplasia (Old way).
• Commonly classified as CIN-I, CIN-II and CIN-
III.
• Currently classified as:
i. Low grade squamous intraepithelial lesion
(LSIL/ CIN-I).
ii. High grade squamous intraepithelial lesion
(HSIL/ CIN-II, CIN-III).
Cervical intraepithelial neoplasia (CIN)
• The classification is based on expansion of the
immature cell layer from its normal basal
location to upwards toward the superficial
layer.
i. CIN-1 (LSIL )
ii. CIN-2 (HSIL)
iii. CIN-3 (HSIL)
Cervical intraepithelial neoplasia (CIN)
• LSIL (CIN-1): If the atypical, immature
squamous cells are confined to the lower one
third of the epithelium.
• HSIL (CIN-2): If the atypical cells expand to two
thirds of the epithelial thickness.
• HSIL (CIN-3): Total replacement of all the layers
of epithelium by atypical cells.
CIN: Progression/ Fate
• LSIL (CIN-I): Does not progress directly to
invasive carcinoma and in fact most cases
regress spontaneously.
• HSIL (CIN-II, III): increased cellular proliferation
may become irreversible and lead to a fully
transformed malignancy.
• LSIL (Low grade lesion) are ten times more
common than HSIL (High grade lesion).
Carcinoma in Situ (CIS)
• Atypical malignant cells involving whole
thickness of the cervical epithelium but does not
cross the epithelial basement membrane is
called carcinoma in situ.
• It is the malignant condition of the cervix. But
the malignant cells do not cross the basement
membrane.
• If the malignant cells cross the basement
membrane it is called invasive carcinoma not
CERVICAL CARCINOMA
• Types:
• Squamous cell carcinoma (80%).
• Adenocarcinoma.
• Adenosquamous carcinoma.
• Neuroendocrine carcinoma.
Cervical Cancer Screening and Prevention
• The pap test screening is effective in
preventing cervical cancer as cancers arise
from precursor lesions over the years. And
shed abnormal cells that can be detected on
cytological examination (Pap test).
• In general first pap smear at age 21 years or 3
years of onset of sexual activity and thereafter
every 3 years. After 30, women with normal
cytology may be screened in every 5 years.
Cytologic screening by Pap test
• Pap tests are cytologic preparations of
exfoliated cells from the cervical
transformation zone. Cells are stained with the
Papanicolaou method (Pap stain).
• The cellular changes on the stained smears
identify the normal, LSIL and HSIL.
• HPV DNA testing can also be done on cervical
cytology for screening.
Cervical Cancer Screening and Prevention
• If Pap test is abnormal, a colposcopic
examination of the cervix is performed to
identify abnormal area.
• The mucosa is examined with a magnifying
glass following application of acetic acid (VIA
test), which highlights abnormal epithelium as
white spots (acetowhite areas).
• Abnormal appearing areas are biopsied.
Management of CIN
• Women with LSIL is followed conservatively
with repeat smears and close follow-up. Some
gynecologists perform local ablation
(cryotherapy).
• HSILs are treated with cervical conization
(superficial Excision).
HPV Vaccination
• A new aspect of cervical cancer prevention is
vaccination against high-risk oncogenic HPVs.
• It is now recommended for all girls and boys by
age 11 to 12 years, as well as young men and
women up to age 26 years.
• The vaccines offer protection from HPV for up
to 10 years
Diseases of the Ovary
Diseases of the Ovary
Diseases mainly are:
1. Functional or Benign cysts
2. Ovarian Tumour
Diseases of the Ovary
• Nonneoplastic and Functional Cysts are:
1. Follicular cyst.
2. Luteal cyst.
3. Polycystic ovaries.
Follicle and Luteal Cysts
• Cystic follicles are very common in the ovary.
They originate from unruptured graafian
follicles or in follicles that have ruptured and
immediately sealed.
• These cysts are usually multiple. They range
in size up to 2 cm in diameter, are filled with a
clear serous fluid.
Polycystic Ovaries
• Polycystic ovarian syndrome (PCOS) is a
complex endocrine disorder characterized by:
i. Hyperandrogenism
ii. menstrual abnormalities
iii. polycystic ovaries
iv. chronic anovulation
v. decreased fertility.
Polycystic Ovaries
• Formerly called Stein Leventhal syndrome,
affects 6-10% of reproductive age women
worldwide.
• It is also associated with obesity, type 2
diabetes, and premature atherosclerosis.
• Due to an increase in serum estrogen levels,
women with PCOS are at risk for endometrial
hyperplasia and carcinoma.
Ovarian tumor
• 80% of ovarian tumor are benign, benign tumor
occurs mostly in young women between the
ages of 20 and 45 years.
• Malignant tumors are more common in older
women.
• Ovarian cancer accounts for 3% of all cancers
in females and is the fifth most common cause
of death due to cancer.
Ovarian tumor
• Because most ovarian cancers have spread
beyond the ovary by the time of diagnosis,
account for a disproportionate number of
deaths.
• Categorizes into Benign, Borderline and
Malignant
• Surface epithelial tumors are most common.
Among surface epithelial tumor, serous tumors
are more common.
Classification
• Primary tumours:
• SURFACE EPITHELIAL-STROMAL
TUMORS
• SEX CORD–STROMAL TUMORS
• GERM CELL TUMORS
• Secondary metastatic tumour to ovary:
• From Colon, Appendix, Gastric carcinoma.
Classification
• Surface epithelial stromal tumors are most
common.
• Among surface epithelial stromal tumors
serous tumors are more common
(approximately 40% of all cancers of the
ovary).
• Mucinous tumors account for about 20% to
1.Surface epithelial-Stromal Tumor
1. Serous tumors
i. Benign (cystadenoma)
ii. Borderline tumors (serous borderline
tumor)
iii. Malignant (serous adenocarcinoma)
2. Mucinous tumors
3. Endometrioid tumors
4. Clear cell tumors
5. Transitional cell tumors
2. Sex Cord–Stromal Tumors
1. Granulosa tumors
2. Fibromas
3. Fibrothecomas
4. Thecomas
5. Sertoli cell tumors
6. Leydig cell tumors
3.Germ Cell Tumors
1. Teratoma
2. Dysgerminoma.
3. Yolk sac tumor.
4. Mixed germ cell tumour.
Teratoma
• Teratoma are the tumors arising from the
component from more than one germ layer.
• Teratoma are bilateral in 10% to 15% of cases.
• Characteristically they are unilocular cysts
containing hair and sebaceous material, bones,
teeth, cartilage.
Teratoma Classification
i. Immature (malignant)
ii. Mature :
iii. Monodermal or special(struma ovarii)
• Mature :
i. Solid
ii. Cystic (dermoid cyst)
Hormone producing tumors of ovary
Granulosa cell tumor Estrogen
Thecoma Estrogen
Leydig cell tumor Androgen
Sertoli cell tumor Androgen, Estrogen
Struma ovari Thyroxine
Diseases of the Body of uterus
and Placenta
Endometriosis
• Affects approximately 6% to 10% of women.
Presence of endometrial glands and stroma
outside of the uterus is called endometriosis.
• It often causes infertility, dysmenorrhea
(painful menstruation) and pelvic pain.
• Adenomyosis:
Adenomyosis is the presence of endometrial
glands and stroma in the myometrium.
Endometriosis
• Sites of endometriosis:
(1) Ovary (Commonest)
(2) Uterine ligaments
(3) Rectovaginal septum
(4) Cul de sac
(5) Pelvic peritoneum
(6) Large and small bowel and appendix;
(7) Mucosa of the cervix, vagina, and
fallopian tubes
(8) Laparotomy scars.
Endometriosis
• The regurgitation theory (retrograde flow of
menstrual endometrium).
• The benign metastases theory (endometrial
tissue spreadvia blood vessels and lymphatic
channels).
• The metaplastic theory (arises directly from
mesothelium of pelvis or abdomen)
Ectopic Pregnancy
• Implantation of the fetus in any site other than
a normal intrauterine location. Occurs about
one in every 150 pregnancies.
• The most common site is the fallopian tube
(approximately 90% of cases).
• Rupture of a tubal pregnancy is a medical
emergency.
Ectopic Pregnancy
• The predisposing condition is prior pelvic
inflammatory disease (PID) resulting in
fallopian tube scarring or fibrosis.
• Peritubal scarring and adhesions caused by
appendicitis, endometriosis, and previous
surgery are risk factor.
Ectopic Pregnancy
• Abdominal pain, vaginal bleeding, hemorrhagic
shock with signs of an acute abdomen.
• Despite advances in early diagnosis, ectopic
pregnancy still accounts for 4% to 10% of
pregnancy related deaths.
Ectopic Pregnancy
• Sites of ectopic pregnancy:
i. Fallopian tubes (∼90%)
ii. Ovaries
iii. Abdominal cavity
iv. Intrauterine portion of the fallopian tube
(cornual pregnancy).
Tumors of the myometrium
(Leiomyoma or Fibroid)
Leiomyoma (Fibroid)
• Uterine leiomyoma is the benign tumour of the
smooth muscle of myometrium.
• Perhaps most common tumor in female.
Leiomyoma may occur singly, but more often
are multiple.
• They can be within the myometrium
(intramural), beneath the endometrium
(submucosal) or beneath the serosa
(subserosal).
Leiomyoma (Fibroid)
• Leiomyomas of the uterus, even when large or
numerous, may be asymptomatic. Leiomyoma
may cause:
• Abnormal uterine bleeding
• Urinary frequency due to compression of the
bladder
• Sudden pain from infarction of a large or
pedunculated tumor
• Impaired fertility.
Leiomyoma (Fibroid)
• Leiomyoma in pregnant women:
i. Increase the frequency of spontaneous
abortion
ii. Fetal malpresentation
iii. Uterine inertia
iv. Postpartum hemorrhage.
• Malignant leiomyoma is rare and is called
leiomyosarcoma.
Abnormal Uterine Bleeding
Dysfunctional Uterine Bleeding
Abnormal Uterine Bleeding
• Abnormal uterine bleeding can be caused
by pathologic conditions, such as:
i. Chronic endometritis
ii. Endometrial polyps
iii. Leiomyomas
iv. Endometrial neoplasms.
Abnormal uterine bleeding
• Prepuberty:
Precocious puberty (hypothalamic,
pituitary, or ovarian origin)
• Adolescence:
i. Anovulatory cycle
ii. Coagulation disorders
• Reproductive age:
1. Abortion
2. Trophoblastic disease
3. Ectopic pregnancy
4. Leiomyoma
5. Adenomyosis
6. Endometrial polyps
7. Endometrial hyperplasia
8. Endometrial carcinoma
• Perimenopausal and Postmenopausal:
1. Endometrial carcinoma,
2. Endometrial hyperplasia
3. Endometrial polyps
4. Anovulatory cycle
5. Cystic atrophy of the endometrium.
Dysfunctional Uterine Bleeding (DUB)
• Uterine bleeding due to hormonal disturbances
not caused by any underlying organic
(structural) abnormality.
1. Anovulatory cycle.
2. Ovulatory dysfunctional bleeding
(inadequate luteal phase).
3. Irregular shedding of endometrium.
Endometrial Polyp
Endometrial Polyp
• Endometrial polyps are exophytic masses of
variable size that project into the endometrial
cavity.
• Endometrial Polyps may be asymptomatic or
may cause abnormal bleeding (intramenstrual,
menometrorrhagia, postmenopausal bleeding).
• Endometrial Polyps can be a cause of
infertility.
Endometrial Polyp
• Endometrial polyps have been observed in
association with the administration of
tamoxifen.
• tamoxifen is often used in the therapy of breast
cancer due to its anti-estrogenic activity on the
breast.
Endometrial Hyperplasia
Endometrial Hyperplasia
• An increased proliferation of the endometrial
glands , resulting in an increased gland-to-
stroma ratio.
• Endometrial hyperplasia is an important cause
of abnormal uterine bleeding.
• A frequent precursor to the endometrial
carcinoma.
• It is divided into non-atypical and atypical
hyperplasia.
Endometrial Hyperplasia
• Endometrial hyperplasia is associated with
prolonged estrogenic stimulation of the
endometrium.
• can be due to:
i. Chronic anovulation
ii. Increased estrogen production from
endogenous sources, or exogenous estrogen.
iii. Obesity
iv. Polycystic ovarian syndrome (pcos)
v. Prolonged administration of estrogenic
substances (estrogen replacement therapy/ HRT)
Malignant tumors of endometrium
Most common malignant tumor of female genital
tract.
1.Type I or Endometrioid carcinoma
2.Type II or Serous Carcinoma
i.Serous carcinoma.
ii.Clear cell carcinoma.
iii.Malignant mixed mullerian tumour.
Fallopian Tube diseases
• Inflammation (Salpingitis):
i. Gonococcus.
ii. Chlamydiae.
iii. Tubercular.
Salphingitis causes scarring and fibrosis which
causes infirtility and ectopic pregnancy.
• Ectopic pregnancy
• Endometriosis
Gestational and Placental
Disorders
Gestational and Placental Disorders
1. Disorders of Early pregnancy
i.Spontaneous abortion
ii.Ectopic pregnancy
2. Disorders of late pregnancy
i.Placental implantation
abnormalities
ii.Twin placenta
iii.Placental infections
3. Gestational trophoblastic Disease
Placental abnormalities
• Placenta accreta:
Adherence of placenta directly to the
myometrium.
• Placenta previa :
Implantation of placenta in the lower
uterine segment or cervix.
• Placental inflammation and infections:
Placentitis, Villitis, Chorioamnionitis
• PreEclampsia and Eclampsia.
PreEclampsia and
Eclampsia
PreEclampsia
• Preeclampsia is a systemic syndrome
characterized clinically with hypertension,
edema, and proteinuria due to widespread
maternal endothelial dysfunction.
• Occurs in about 3% to 5% of pregnant women in
the last trimester and in primiparas.
• Other complications include hypercoagulability,
acute renal failure, and pulmonary edema.
Riskfactors of PreEclampsia
Eclampsia
• More severe form of Preeclampsia associated
with convulsion, it is termed as Eclampsia.
• The onset is typically characterized by
hypertension, edema and proteinuria.
• Headache and visual disturbances are serious
events with convulsions and eventual coma.
Management of preeclampsia/Eclampsia
• For term pregnancies, delivery is the treatment
of choice regardless of disease severity.
• Eclampsia, severe preeclampsia with maternal
end-organ dysfunction, fetal compromise, are
indications for delivery regardless of
gestational age.
• Proteinuria, Hypertension, Convulsion and
other symptoms disappear within 1 to 2 weeks
after delivery.
Gestational and Placental Disorders
1. Disorders of Early pregnancy
i.Spontaneous abortion
ii.Ectopic pregnancy
2. Disorders of late pregnancy
i.Placental implantation
abnormalities
ii.Twin placenta
iii.Placental infections
3. Gestational trophoblastic Disease
3. Gestational trophoblastic Disease
• Gestational trophoblastic disease
encompasses a spectrum of tumors and
tumor-like conditions characterized by
proliferation of placental tissue.
Gestational trophoblastic Disease:
Classification
1. Hydatidiform mole (molar pregnancy)
i. Complete mole
ii. Partial mole
iii. Invasive mole
2. Choriocarcinoma.
3. Placental site trophoblastic tumor (PSTT)
Hydatidiform mole (Molar Pregnancy)
• A molar pregnancy is a benign tumor that
develops in the uterus when an egg is
fertilized, but instead of a normal viable
pregnancy the placenta develops into
abnormal mass of cysts or graph like
structure.
• A molar pregnancy may seem like a normal
pregnancy at first.
Signs and Symptoms
• Dark brown to bright red vaginal bleeding during
the first trimester.
• Severe nausea and vomiting.
• Sometimes vaginal passage of grape-like cysts.
• Rapid uterine growth — the uterus is too large for
the stage of pregnancy.
• High blood pressure.
• Anaemia.
Hydatidiform mole (Molar Pregnancy)
• Hydatidiform moles are associated with an
increased risk of recurrent molar pregnancy or
choriocarcinoma.
• Usually diagnosed during early pregnancy
(average 9 weeks).
• Risk increases in teens and between the ages
of 40 and 50 years and mostly in primiparas.
Complete mole
• Complete mole results from fertilization of an
egg that has lost its chromosomes (empty
ovum) and the genetic material is completely
paternally derived.
• 90% have a 46,XX karyotype, derived from
duplication of the genetic material of one
sperm.
• In complete moles the embryo dies very early
in development and therefore is usually not
Partial mole
• Partial moles result from fertilization of an egg
with two sperm.
• In these moles the karyotype is triploid
(69,XXY) or even occasionally tetraploid
(92,XXXY).
• Some fetal tissues are typically present. But
pregnancy couldnot be contimued.
Complete and Partial Mole
Partial mole VS Complete mole
Feature Partial mole Complete mole
Karyotype Triploid, Tetraploid 46,XX (46,XY)
Villous edema Some villi All villi
Trophoblast Focal; slight Diffuse;
proliferation circumferential
Atypia Absent Often present
Serum hCG Less elevated Elevated
HCG in Tissue + ++++
Behaviour Rarely 2% risk of
Choriocarcinoma Choriocarcinoma
Invasive mole
• Mole that penetrate and may even perforate
the uterine wall.
• May cause uterine rupture.
• The tumor is locally destructive and may
invade parametrial tissue and blood vessels.
• Hydropic villi may embolize to distant sites
such as lungs and brain.
Choriocarcinoma
• Gestational choriocarcinoma is a malignant
neoplasm of trophoblastic cells.
• Choriocarcinoma is rapidly invasive and
metastasizes widely, but once identified
responds well to chemotherapy.
• The chemotherapy result is nearly 100%
remission and a high rate of cures.
Question??
• Tell a tumor marker which is elevated in normal
physiological condition, in benign tumor and in
malignant tumor???
• Beta HcG (Pregnancy, Molar pregnancy,
Choriocarcinoma)
Assisted Reproduction/ ART/ IVF/
(Test Tube Baby)
Assisted Reproduction
When a couple is sub-fertile or infertile they need
Assisted Reproduction to have a child.
1. Replace source of gametes
Sperm, oocyte or zygote donors
2. Aid in the fertilization process (ART)
3. Replace/bypass the uterus
Surrogate mother
Assisted Reproductive Technologies
(ART)
• In vitro fertilization (IVF)
• Intracytoplasmic sperm injection (ICSI)
• Gamete intrafallopian transfer (GIFT)
• Zygote intrafallopian transfer (GIFT)
In Vitro Fertilization (IVF)
• IVF is the uniting of egg/ovum and sperm in
vitro (in the lab).
• Subsequently the embryos are transferred into
the uterus through the cervix and pregnancy is
allowed to begin.
• Retrival of maturing eggs done via laparoscopy
.
• Each egg is incubated with > 3.5 x 106 sperms.
Intracytoplasmic sperm injection (ICSI)
• Intracytoplasmic sperm injection (ICSI), is
an in vitro fertilization procedure in which a
single sperm is injected directly into an egg.
• This procedure is used to overcome male
infertility problems, when father has low
sperm count or large number of abnormal
sperm.
ICSI
• IVF where sperm is injected into oocyte
GIFT, ZIFT
• Gamete intrafallopian transfer (GIFT)
Gametes are collected and placed into a
woman’s oviduct (Fallopian tube) where
fertilization occurs.
• Zygote intrafallopian transfer (ZIFT)
Gametes are collected and fertilized by in
vitro fertilization before transfer to the
oviduct.
Surrogate Mothers
• Surrogate mothers:
– Inseminated with father’s semen, using
surrogates own oocytes.
– Or may be implanted with a zygote from
couple’s gametes
• Legal rights of surrogate mothers vary by state
and country.
Hormone replacement
therapy (HRT)
Hormone replacement therapy (HRT)
• Hormone replacement therapy (HRT) is a
treatment used to relieve/lowering the
symptoms of the menopause.
• It replaces female hormone (estrogen) that
is at a lower level as someone approach the
menopause.
Symptoms of Menopause
• Hot Flashes
• Night sweats
• Sleep Problems
• Vaginal dryness
• Reduced libido
• Depression
• Trouble concentrating or remembering things
DRUGS USED IN HRT
• ESTROGEN
• PROGESTERONE
• TIBOLONE
• RALOXIFENE
• BISPHOSPHONATES
• ANDROGENS
HRT routes of administration
• ORAL
• NTRAMUSCULAR INJECTION
• IMPLANTS
• IUCD
• VAGINAL TABLETS AND RINGS
• SKIN PATCHES
Contraindications of HRT
• Breast cancer
• Coronary Heart Disease
• Previous blood clot
• Stroke
• Liver disease
• Uterine cancer
• High Triglycerides
• Gallbladder disease
Thank you All