3-What Is Endometrial Hyperplasia?

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1- Anatomy: The female reproductive organs can be subdivided into the internal and external

genitalia (see the images below). The internal genitalia are those organs that are within the true
pelvis. These include the vagina, uterus, cervix, uterine tubes (oviducts or fallopian tubes), and
ovaries. The external genitalia lie outside the true pelvis. These include the perineum, mons
pubis, clitoris, urethral (urinary) meatus, labia majora and minora, vestibule, greater vestibular
(Bartholin) glands, Skene glands, and periurethral area.

2- Abnormal uterine bleeding is bleeding between monthly periods, prolonged bleeding or an


extremely heavy period. AUB can occur when the ovaries do not release an egg. Changes in
hormone levels cause your period to be later or earlier. Your period may sometimes be heavier
than normal. AUB is more common in teenagers or in premenopausal women. Women who are
overweight also may be more likely to have AUB.
In many women, AUB is caused by a hormone imbalance. It can also occur due to following
causes:
 Thickening of the uterine wall or lining
 Uterine fibroids
 Uterine polyps
 Cancers of ovaries, uterus, cervix, or vagina
 Bleeding disorders or problems with blood clotting
 Polycystic ovary syndrome
 Severe weight loss
 Hormonal birth control, such as birth control pills or intrauterine devices (IUD)
 Excessive weight gain or loss (more than 10 pounds or 4.5 kilograms)
 Infection of the uterus or cervix

3- What is endometrial hyperplasia?


Endometrial hyperplasia is a condition in which the endometrium (lining of the uterus) is
abnormally thick. There are four types of endometrial hyperplasia. The types vary by the
amount of abnormal cells and the presence of cell changes. These types are: simple
endometrial hyperplasia, complex endometrial hyperplasia, simple atypical endometrial
hyperplasia, and complex atypical endometrial hyperplasia.
Endometrial hyperplasia is caused by too much estrogen or not enough progesterone. Both of
these hormones play roles in the menstrual cycle. Estrogen makes the cells grow, while
progesterone signals the shedding of the cells. A hormonal imbalance can produce too many
cells or abnormal cells.
The primary symptom of endometrial hyperplasia is abnormal menstrual bleeding.:

 Menstrual bleeding that is heavier or longer lasting than usual.


 Menstrual cycles (amount of time between periods) that are shorter than 21 days.
 Menstrual bleeding between menstrual periods.
 Not having a period (pre-menopause).
 Post-menopause uterine bleeding.

4-Estrogens are hormones that are important for sexual and reproductive development,
mainly in women. They are also referred to as female sex hormones.
Estrone: This type of estrogen is present in the body after menopause. It is a weaker form of
estrogen and one that the body can convert to other forms of estrogen, as necessary.
Estradiol :Both males and females produce estradiol, and it is the most common type of
estrogen in females during their reproductive years.
Too much estradiol may result in acne, loss of sex drive, osteoporosis, and depression. Very
high levels can increase the risk of uterine and breast cancer. However, low levels can result in
weight gain and cardiovascular disease.
Estriol : Levels of estriol rise during pregnancy, as it helps the uterus grow and prepares the
body for delivery. Estriol levels peak just before birth.

5-Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs
which prevent estrogens like estradiol from mediating their biological effects in the body. They
act by blocking the estrogen receptor (ER) and/or inhibiting or suppressing estrogen
production.
6 – NORETHISTHORNE: progestins like norethisterone exert their effects on target cells via
binding to progesterone receptors that result in downstream changes to target genes.
Contraceptive efficacy is derived mainly from changes to the cervical mucus, wherein
norethisterone increases the cell content and viscosity of the mucous to impede sperm
transport and migration .Norethisterone also induces a variety of changes to the endometrium
- including atrophy, irregular secretion, and suppressed proliferation - that make it inhospitable
for implantation. Working via a negative feedback loop, norethisterone also acts on both the
hypothalamus and anterior pituitary to suppress the release of follicle-stimulating hormone
(FSH) and luteinizing hormone (LH) from the anterior pituitary. Suppression of these
hormones prevents follicular development, ovulation, and corpus luteum development. 12
CASE2:
1-Progestins are synthetic forms of the body’s naturally-occurring
hormone progesterone. Progestins were designed to interact with progesterone receptors in
the body in order to cause progesterone-like effects. This means that they do some of what the
body’s natural progesterone does. For instance, progestins can cause changes to
the endometrium (the lining of the uterus) that prevent it from proliferating (building up) too
much, and that can help it support implantation and the continuation of an early pregnancy.
Progestins prevent pregnancy by inhibiting ovulation and reducing the amount and stretchiness
of cervical mucus, making it unfriendly to sperm that are trying to enter the uterus 
2-Antiprogestins are synthetic steroids which have a high affinity for progesterone receptors,
preventing progesterone from exerting its biological effects. They act as true receptor
antagonists, preventing the uterine effects of progesterone without initially decreasing serum
progesterone concentrations.. Antiprogestogens are used as abortifacients and emergency
contraceptives and in the treatment of uterine fibroids. They are also being studied in the
treatment of breast cancer.
3- Endometriosis (en-doe-me-tree-O-sis) is an often painful disorder in which tissue similar to
the tissue that normally lines the inside of your uterus — the endometrium — grows outside
your uterus. Endometriosis most commonly involves your ovaries, fallopian tubes and the tissue
lining your pelvis. Rarely, endometrial tissue may spread beyond pelvic organs.
With endometriosis, the endometrial-like tissue acts as endometrial tissue would — it thickens,
breaks down and bleeds with each menstrual cycle. But because this tissue has no way to exit
your body, it becomes trapped. When endometriosis involves the ovaries, cysts called
endometriomas may form. Surrounding tissue can become irritated, eventually developing scar
tissue and adhesions — abnormal bands of fibrous tissue that can cause pelvic tissues and
organs to stick to each other.
Endometriosis can cause pain — sometimes severe — especially during menstrual periods.
Fertility problems also may develop. Fortunately, effective treatments are available.
Common signs and symptoms of endometriosis include:
 Painful periods (dysmenorrhea). Pelvic pain and cramping may begin before and extend
several days into a menstrual period. You may also have lower back and abdominal pain.
 Pain with intercourse. Pain during or after sex is common with endometriosis.
 Pain with bowel movements or urination. You're most likely to experience these
symptoms during a menstrual period.
 Excessive bleeding. You may experience occasional heavy menstrual periods or bleeding
between periods (intermenstrual bleeding).
 Infertility. Sometimes, endometriosis is first diagnosed in those seeking treatment for
infertility.
 Other signs and symptoms. You may experience fatigue, diarrhea, constipation,
bloating or nausea, especially during menstrual periods.
4- DANAZOL : As a gonadotropin inhibitor, danazol suppresses the pituitary-ovarian axis
possibly by inhibiting the output of pituitary gonadotropins. Danazol also depresses the
preovulatory surge in output of follicle-stimulating hormone (FSH) and luteinizing hormone
(LH), thereby reducing ovarian estrogen production. Another mechanism of action by which
danazol may use to facilitate regression of endometriosis is by decreasing IgG, IgM, and IgA
concentrations, as well as phospholipid and IgG isotope autoantibodies. In the treatment of
endometriosis, as a consequence of suppression of ovarian function, danazol causes both
normal and ectopic endometrial tissues to become inactive and atrophic. This leads to
anovulation and associated amenorrhea. 
5- Naproxen : As with other non-selective NSAIDs, naproxen exerts it's clinical effects by
blocking COX-1 and COX-2 enzymes leading to decreased prostaglandin synthesis

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