Estrogen

Uterine factor

Ans. is d i.e Triglycerides                  

Estrogen causes : — plasma LDL

— T plasma HDL

—  T Triglycerides

• It also increases blood coagulability by inducing formation of clotting factors
• Estrogen increases lithogenesity of bile.

Ans. is c i.e Bone mass   

Before seeing any Reference for the Question let’s rule out some options.

• Estrogen administration will exert a negative feedback on gonadotropin secretion and decreases Gonadotropin secretion rather than increasing it (Option ‘a’ ruled out).

As I have already discussed in previous Question -Estrogen decreases LDL and not increases it (ruling out Option `b).

Now we are left with 2 options, Option ‘c’ i.e. Bone mass and Option ‘rile. Muscle mass.

• Estrogen given as hormone replacement therapy is most beneficial in preventing osteoporosis i.e it must be increasing bone mass.

So, Option ‘c’seems to be correct.

Now have a look what texts have to say :

Estrogen helps to maintain bone mass and skeletal integrity thereby protecting against osteoporosis.

Effect of estrogen on bones :          

• Estrogen causes increased osteoblastic activity in the bones.
• It is important in maintaining bone mass primarily by retarding bone resorption. The major action of estrogen is directed at reducing the maturation and activity of osteoclasts, by modifying regulatory cytokine signals from osteoblasts.

• The action of estrogen and progesterone result in increased expression of bone matrix proteins such as osteonectin, osteocalcin, collagen and alkaline phosphatase.

Extra Edge :

An overveiw of osteoporosis

Risk factors for osteoporosis

Diagnosis : Bone Mineral Density Measurement (BMD)

• Dual X-ray Absorptiometry (DXA) of hip and spine is the primary technique for BMD assessment.
• BMD is expressed as a T score, which is the number of standard deviations from the mean for a young healthy woman.
• A T score above —1 is considered normal, a value between —1 and —2.5 denotes osteopenia and a score below —2.5 indicates osteoporosis.
• Evaluation of BMD by DXA is recommended for all women aged 65 and older, regardless of risk factors and for younger postmenopausal women with 1 or more risk factors.

None

Ans. is a i.e. Peripheral aromatization of androstenedione

• In menopause estrogen levels decrease by 66%.
• Main source of estrogen production postmenopausaly is by peripheral aromatization of androstenedione.
• Main estrogen after menopause – oestrone.

Also know : • Main estrogen during reproductive year is oestradiol.°

• Main estrogen in pregnancy is oestriol.°

Secretory function on endometrium

REF: Ganong’s 22^ed chapter 23

Before ovulation REF: Ganong’s 22nd ed p. 24

Post menopausal estradiol levels: 35 pg / L

Aromatase

Estrogens increase HDL cholesterol.

Ref: KDT 5th Edition, Pages 274-9; KDT 6th Edition, Page 229; Harrison’s Principles of Internal Medicine, 16th Edition, Chapter 30; Novak’s Textbook of Gynecology, 14th Edition, Pages 272-73

The effects of oestrogen on the skeletal system includes:

They promote the development of female secondary sexual characteristics, such as breast development.

So it is not used in treatment of gynaecomastia.

Estrogen and other hormones are given to postmenopausal women as a part of hormone replacement therapy (HRT) in order to prevent osteoporosis as well as treat the symptoms of menopause.

About 80% of breast cancers rely on supplies of the hormone estrogen to grow: they are known as hormone-sensitive or hormone-receptor-positive cancers.

Suppression of production of estrogen in the body is a treatment for these cancers.

Estrogens cause intrahepatic cholestasis by altering the composition of the lipid membrane and inhibiting the rate of secretion of bile into the canaliculi.

Estrogens directly regulate osteoblasts and increase the synthesis of type I collagen, osteocalcin, osteopontin, osteonectin, alkaline phosphatase, and other markers of differentiated osteoblasts.

Estrogens also increase osteocyte survival by inhibiting apoptosis.

However, the major effect of estrogens is to decrease the number and activity of osteoclasts.

Much of the action of estrogens on osteoclasts appears to be mediated by altering cytokine (both paracrine and autocrine) signals from osteoblasts.

Estrogens decrease osteoblast and stromal cell production of the osteoclast-stimulating cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)- and increase the production of IGF-1, bone morphogenic protein (BMP)-6, and transforming growth factor (TGF) Beta which are antiresorptive.

Ref: Levin E.R., Hammes S.R. (2011). Chapter 40. Estrogens and Progestins. In L.L. Brunton, B.A. Chabner, B.C. Knollmann (Eds), Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12e.

The major estrogens produced by women are estradiol (estradiol-17, E2), estrone (E1), and estriol (E3).

Estradiol is the major secretory product of the ovary.

Although some estrone is produced in the ovary, most estrone and estriol are formed in the liver from estradiol or in peripheral tissues from androstenedione and other androgens. 

Over time, the estrogen and progestin contents of COCs have been reduced remarkably to minimize hormone-related adverse effects.

Currently, the lowest acceptable dose is limited by their ability to prevent pregnancy and unacceptable breakthrough bleeding. Although daily estrogen content varies from 20 to 50 g of ethinyl estradiol, most contain 35 µg or less.

Low-dose COCs usually contains 20 µg ethinyl estradiol.

Aromatase enzyme: In a normal ovary, LH acts on the theca interstitial stromal cells, whereas FSH acts on granulosa cells. In response to LH the thecal cells secretes androgen, and the produced androsendione is converted in the granulosa cells to estrogen by the action of aromatase enzyme.

Ref: Physiology By James N. Pasley 2nd Edition, Page 145 ; Androgens in health and disease By William J. Bremne Page 84 ; Padé approximation and its applications: Diagnosis and management of PCOS, Issue 765, By Luc Wuytack, Page 107

Estrogen is found to induce proliferation of endometrial glands and stroma including vascular endothelium. Progestin is responsible for the secretory differentiation in endometrial glands and decidual type changes in the stroma.

Other effects of estrogen are: 

• Estrogen facilitate the growth of ovarian follicles and increase the motility of uterine tubes. 
• Estrogen increases the growth of ducts in breasts and is responsible for breast enlargement at puberty in girls.
• It is also associated with the development of secondary sexual characters in females.
• It increases libido in humans, by exerting a direct effect on certain neurons in hypothalamus.

C i.e. Aromatase

B i.e. Glycolysis increases

B i.e. Estrogen

Growth spurt at puberty occurs because of androgen & estrogens, but estrogen ultimately terminate growth by causing the epiphyses to fuse to the long bones (epiphysial closure). Once the epiphyses have closed, linear growth ceases.

Patient with sexual precocity are apt to be dwarfed. On the other hand men who were castrated before puberty tend to be tall because their estrogen production is decreased & their epiph^ysis remain open.

These observation suggest that estrogen, rather than androgen, are responsible for bone maturation that ultimately leads to epiphyseal fusion and cessation of growthQ.

Ans. is ‘a’ i.e., Estradiol

o Estradiol is the major estrogen secreted by the ovary.

Ans. is ‘b’ i.e., Ethinylestradiol

o Estradial, estrone and estrial, all three are found in blood, but estradiol is the most potent estrogen.

Ans. is ‘a’ i.e., Reduces HDL

o Estrogens decrease LDL while increase HDL and triglyceride -4 atherosclerosis is rare before menopause.

Ans. is ‘b’ i.e., Used in treatment of gynacomastia

o Estrogen can cause gynaecomastia (not used in gynaecomastia), cholestasis and breast cancer.

o One of the most important use of estrogen is HRT in postmenopausal females.

Ans. is ‘d’ i.e., Diethylstibestrol

Synthetic progesterones

1. Progesterone derivatives —> Medroxyprogesterone, Megestrol, Dydrogesterone, Hydroxyprogesterone, Nomegestrol.

2. 1 9-Nortestosterone derivatives —> Norethindrone, Lynesternol, Allylesterone, Levonorgestrel, Desogestrel, Norgestimate, Gestodene.

Synthetic estrogens

1. Steroidal —-> Ethinylestradiol, mestranol, tibolone.
2. Nonsteroidal —-> Diethylstilbestrol, hexestrol, dienestrol

Ans. is ‘c’ i.e., Breast cancer

Antiestrogens (not estrogen) are used in breast cancer.

Ans. is ‘b’ i.e., Estrogen

o Estrogen is responsible for venous thromboembolism, i.e. leg vein and pulmonary thrombosis.

o Both estrogen and progesterone are responsible for arterial phenomena, i.e. coronary^, and cerebral thrombosis —> MI and stroke

Ans. C i.e. Estrogen

Ans. B: Estrogen

Follicular Phase

Through the influence of a rise in (FSH), five to seven tertiary-stage ovarian follicles are recruited for entry into the next menstrual cycle.

One (or occasionally two) dominant follicles will continue to maturity and secrete increasing amounts of estradiol which initiate the formation of a new layer of endometrium in the uterus, histologically identified as the proliferative endometrium Ovulation

When the egg has matured, it secretes enough estradiol to trigger the acute release of (LH). In the average cycle this LH surge starts around cycle 12th day and may last 48 hours and leads to ovulation.

At the time of ovulation, the cervical mucus is thin and has the property of great elasticity and this is called spinnbarkeiti thread test under estrogenic activity. When viewed under the microscope, the mucus shows characteristic pattern of fern formation, which is due to presence of sodium chloride in the mucus secreted under estrogenic effect. Luteal phase

After ovulation, the residual follicle transforms into the corpus luteum. This corpus luteum will produce Progesterone in addition to estrogens for approximately the next 2 weeks.

Progesterone plays a vital role in converting the proliferative endometrium into a secretory lining receptive for implantation and supportive of the early pregnancy. It raises the body temperature.

Hormonal control

Gonadal

• Estradiol peaks twice, during follicular growth and during the luteal phase.
• Progesterone remains virtually absent prior to ovulation, but becomes critical in the luteal phase and during pregnancy. Many tests for ovulation check for the presence of progesterone.

After ovulation the corpus luteum which develops from the burst follicle and remains in the ovary secretes both estradiol and progesterone.

Hypothalamus and pituitary

These sex hormones come under the influence of the pituitary gland, and both FSH and LH play necessary roles:

• FSH stimulates immature follicles in the ovaries to grow.
• LH triggers ovulation.

The Gonadotropin releasing hormone of the hypothalamus controls the pituitary, yet both the pituitary and the hypothalamus receive feedback from the follicle.

Ans. C: Osteoporosis

Osteoporosis: The most important risk factors for osteoporosis are :

Advanced age (in both men and women) and female sex;

Estrogen deficiency following menopause is correlated with a rapid reduction in bone mineral density, while in men a decrease in testosterone levels has a comparable (but less pronounced) effect

Ans. is ‘d’ i.e., Androgen

Ans. is ‘c’ i.e., Ovary

Ans. is ‘c’ i.e., Estrogen

Consistent with the phenomenon of negative feedback in which the secretion of the target hormone inhibits its trophic hormone, pregesterone inhibits LH and inhibin inhibits FSH.

• Estrogen, whose secretion is stimulated by both LH and FSH, inhibits both LH and FSH.
• Progesterone and estrogen act at both hypothalamic and pituitary levels while inhibin secreted by granulosa cells acts only on the pituitary.
• Under certain conditions, estrogen causes stimulation (positive feedback) rather than inhibition of LH, e.g., at ovulation.

Ans. is ‘a’ i.e., Estrogen

Hepatotoxicity with oral contraceptive pills

• While early formulations of OCPs were associated with frequent serum enzyme elevations, current formulations and hormonal replacement therapy have not been linked to ALT or alkaline phosphatase elevations at rates any higher than occur with placebo.
• Estrogens in OCPs can cause mild inhibition of bilirubin excretion leading to jaundice in patients with inherited forms of bilirubin metabolism such as the Dubin Johnson syndrome.
• It can induce a clinically apparent cholestatic liver injury which typically arises during the first few cycles of therapy, and rarely after the six months.
• It has also been linked to hepatic tumors, both benign and malignant.

Ans. is ‘d’ i.e., Menstruation

It is the lack of progesterone support (progesterone withdrawl) that causes mucosal shedding and bleeding during menstration.

Actions of estrogen

1. Sex organs

• Estrogen brings about pubertal changes in female .
• Growth of uterus, fallopian tube and vagina. 
• Vaginal epithelium gets thickened, stratified and cornified.
• Estrogen induce watery cervical secretion.
• Proliferation of endometrium in preovulatory phase.
• Estrogen sensitizes the uterus to oxytocin.

2. Secondary sex character

• Estrogen produced at puberty causes growth of breast-proliferation of duct and stroma, accumulation of fat.
• Pubic and axillary hair appear.
•  Feminine body contours and behaviour are influenced.
• Acne is common in girls at puberty → due to small amount of androgens produced simultaneously.

3. Metabolic effects

• Estrogens are anabolic
• Estrogens promotes fusion of epiphysis
• Maintain bone mass by reducing bone resorption.
• Promote positive calcium balance by inducing renal I a-hydroxylase.
• Cause salt and water retention.
• Estrogens decrease LDL while increase HDL and triglyceride → atherosclerosis is rare before menopause.
• Blood coagulability increases due to increased synthesis of factor II, VII, IX and X.
• Estrogens increase lithogenicity of bile by increasing cholestrol secretion and decreasing bile secretion.

Ans. is ‘c’ i.e., Both theca and granulosa cells

Ovarian follicle contains two types of cells in preovulatory phase :-

i) Granulosa cells :- Secrete mainly estrogen and very minimal amount of progesterone.

ii) Theca cells (interna & externa) Theca interna cells provide androgen and pregnenolone to granulosa cells to convert them into estrogen and progesterone respectively.

After ovulation, corpus luteum contain two types of cell :-

i) Granulosa luteal cells (formed by luteinization of granulosa cells) :- Produce mainly estrogen and minimal progesterone.

ii) Theca luteal cells (formed by luteinization of theca interna cells) :- Produce mainly progesterone.

Ans. is ‘b’ i.e., Stimulates osteoclasts

Major action of estrogen on bone is to inhibit osteoclastic bone resorption.

Estrogen blocks the action of IL-6, a potent stimulator of osteoclasts.

Estrogen also induces apoptosis of osteoclasts.

Other three options are correct.

Actions of estrogen have been explained in previous sessions.

Ans. is ‘a^‘ i.e., Granulosa cells

Ans is Estrogens

(Condition shown: Spider naevi) 

A spider angioma (also known as a nevus araneus, spider nevus, vascular spider, and spider telangiectasia is a type of telangiectasis (swollen blood vessels) found slightly beneath the skin surface, often containing a central red spot and reddish extensions which radiate outwards like a spider’s web. They are common and may be benign, presenting in around 10–15% of healthy adults and young children

Ans is Estrogen

Ans. is ‘b’ i.e., 11-hydroxylase 

Ans. is ‘c’ i.e., Estrogen