WOMEN GYNACOLOGY-PART-X-INTRA UTERINE DEVICES

OTHER METHODS OF BIRTH CONTROL

INTRA UTERINE DEVICE or IUD is a fashioned historical method to prevent pregnancy by inserting a device into the vigina and make to to stay there to produce longer effects of contraception.

Historically it was rumored that some Arab pagans inorder to prevent the births of several calfs as a burden to their female camels they inserted small stones into their uteruses through their vagina to prevent conception.

This historical basics has been used to develop devices with higher technology.

There are two types of IUDs,the hormonal and non hormonal.The hormonal IUDs contains usually a progestin such as a slow release levonorgestrel.The other nonhormal IUDs contains a copper spring.Both the IUDs are yielding a reversible contraception.The effects of copper IUDs are longer than the hormonal IUDs.The hormonal IUDs like Mirena is found to be effective upto 5 years while as the copper IUDs can give the effects upto 7 years.

The insertion should be done by an experienced physician.

 As seen in the above figure the IUD should be correctly positioned by the help of a speculum a medical device used for inserting a device through any small opening or orifice like vagina.

Before insertion the pelvic portion should be thoroughly examined for any inflammation,injury or infection like chlamydia and gonorrhea.The position and shape of the uterus should be confirmed through the pelvic exam.

During the insertion the vagina is held open by a speculum.The cervix should be grasped by a grasping instrument.The leangth of the uterus must be measured for proper insertion.Now the IUD must be carefully inserted through the cervix by using a narrow tube into the uterus.A short narrow monofilament plastic/nylon string attached to the device should be come and hang out through the vagina for the convenience of the patient to check the IUD position later on at times.

 The above video gives an explanation of the inserting methods.

Mechanisms of Actions

1.Make uterus hostile to the fertilized ovum

2.The endometrium becomes thin and not hospitable to the ovum

3.The cervix become thick and sperm cannot penetrate it.

4.Unimportantly sometimes ovulation is retarded

Advantages:-

1.Longer effects

2.No need to take any systamic medications like pills and injections

3.Most of the released hormone from the hormonal IUDs are absorbed and stay within the uterus by leaving a negligible minute quantity into the system.

4.Reversible contraception

5.Inexpensive as they are made out of plastics.

6.The copper IUDs are totally harmless during breast feeding.But there are no known guarentee for hormonal IUDs.

7.No prior care or preparations needed before sex,but the patient has to check the string at times to ensure the device is staying in proper place.

Disadvantages:-

1.Risks of ectopic pregnancy,the pregnancy happened outside the uterus usually at the tube.

2.Irregular heavier periods and spotting

3.Menstrual cramping and back pain. 

4.Painful intercourse experienced by some women.

5.Rare but serious perforation of uterus.

6.Pelvic pain and inflammation leads to serious infections.

Conraindications:-

1.Patients who take blood hinners like aspirin,warfarin and clopidrogel

2.Those who use copper IUD must avoid exposure to microwaves or any short waves such as ultra violet radiations.

3. Teen agers and women who gave several births are commonly experiencing displacement or expulsion of the device and hence should be careful in their movements.

4.Pelvic infections

WOMEN GYNECOLOGY-PART IX-ANTI PROGESTINS

ANTIPROGESTINS-DRUGS FOR ABORTION

As we have already seen that progestins such as progesterone are the agents aiding and maintaining pregnancy.Any drug which opposes or block the actions of progesterone will result in the termination of pregnancy or abortion.

Although anti estrogens have been available since the late 1950s the first report of an antiprogestin appear only after 1981.In that year a drug which is a glucocorticoid antagonist was reported by the name RU-38486 or simply RU-486 was having some anti gestagenic properties also.Later the drug was named as mifepristone.

Although mifepristone's main use is as a terminator of early pregnancy these anti progestins also are tried for the uses as contraceptives,anti cancer drugs,and agents to induce labour.

Chemistry Structurally mifepristone is related to progesterone as a seroidal compound.It is a derivative of norethindrone (a progestin with a methyl group at the 19 th position of its steroidal structure) with a dimethyl-aminophenyl substituent at the 11-b position.

Mechanism The mechanism of action of mifepristone is that because of its similarity in chemical structure to progesterone it competitively inhibit its receptors and block the pregnancy protecting effect of progesterone  at the sensitive tissues like uterus, and thereby causes early contraction of the uterus and terminate the pregnancy.

But mifepristone when present alone in the absence of progesterone it will act as a weak progestin by acting as a partial agonist.

Mifepristone also act on the progesterone sensitive tissues of ovary.If given for a short period in the later follicular phase of the menstrual cycle,it delays ovulation by depressing LH surge.If it has been given frequently or continuously it can prevent ovulation but not in all cases.

If administered for several days in mid or late luteal phase mifepristone disturb the development of the secretory endometrium and causes menses.

Mifepristone is also having effects oncervix,myometrium,ectopic endometrial tissue,breast cancers,and meningiomas

 

WOMEN GYNACOLOGY-PART-VIII-CONTRACEPTIVE PILLS-HEALTH BENEFITS

BIRTH CONTROL PILLS-OTHER BENEFITS

The birth control pills have proved that they have some beneficial effects on the body other than their contraceptive effects.The modern studies have given some useful positive data.

The combination oral contraceptives have been well accepted over a decade for their substantial health benefits unrelated to their birth control uses.These include their beneficial effects on ovarian and endometrial cancers,a number of menstrual disorders,and many other diseases.

Oral contraceptives reduces the risks of ovarian and endometrial cancers within six months of use.The incidences of these diseases have been reduced by 50% after two years of use.More interestingly it is found that these beneficial protective effects of the oral contraceptives are persisting for 15 years after their use is stopped.These agents also beneficial by decreasing the incidences of ovarian cysts and benign fibrocystic breast disease.

Oral contraceptives also give beneficial effects on regulating menstruation,reducing blood losses,reducing the incidences of iron deficiency anemia,dysmenorrhea,and premenstrual tensions.

Also these combination pills reduces pelvic inflammation,ectopic pregnancies(pregnancy outside the uterus),and ameliorating or reducing endometriosis.

Conclusively it is beleived that combination oral contraceptives prevent thousands of deaths,episodes of various diseases and cases of hospitalizations.Hence fertility regulation by oral contraceptives is safer than pregnancy for most women.

WOMEN GYNECOLOGY-PART-VII-BIRTH CONTROL METHODS AND SAFETY

FEMALE CONTRACEPTION-PREVENTION OF PREGNANCY 

Phases of Menstrual Cycle

Normally a total menstrual cycle contains 28 days including the 7 days duration of menses.This may be varied according to some physiological variables such as genetics,obesity,weight,height and the tropical environments.Some pathological conditions also may cause variations in menstrual cycle.

The menstrual cycle depends on the stimulation and secretions of the hypohalamus-anterior pituitary axis,anterior pituitary-ovary  axis,followed by ovarian secretions which control the final and end female parts such as the uterus,the cervix and the vagina.These secretions and effects are generally in a pulsative manner. 

A normal menstrual cycle contains three phases as follows:-

Follicular Phase in which the Graafian follicles by the action of FSH (follicular stimulating hormone) from the anterior pituitary develops and grow and begin to secrete estrogens (estradiol,estriol,and estrone).This phase is composed of approximately 9 days and a slow pulsative decrease of FSH and LH occurs due to a feed back mechanism by estrogens at hypothalamus- anterior pituitary level.

Ovulation Phase which begins on the 10 th day at which a fully developed follicle separates from the ovary and shed into the lumen of the Fallopian tube.In this stage again a pulsative increase of LH occurs and in the empty space from which the ovum detached from the ovary an yellow gland known as Corpus Luteum develops by the action of LH.The duration of this phase is only one day.

Lutinizing Phase Which starts at which the ovulation completed.Lutinizing Hormone helps to develop corpus luteum at the gap left by the detached ovum.This starts almost at the midcycle and last for the rest of the period.At the seventeenth day the peak levels of esrogen and progesterone occur.The FSH level is decreased and LH level increased.
End of the cycle If no fertilization happened the carpus luteum ceased to function,after several days steroid levels drop,and menstruation occurs.The luteal phase is thus controlled by the limited 14 days life time of corpus luteum.The entire sysem then resets and a new menstrual cycle occurs.

Hormonal Conraceptions

Prelude 1.These are the most effective drugs
2.A variey of hormonal derivatives with different combinations,doses and side effects are available.
3.These drugs are mostly used by young and healthy people to prevent pregnancy.
4.In addition to their contraceptive effects these medicines also have substantial health benefits.
5.Because of use of different compounds in different combinations and strengths and in different doses no one can compare or extrapolate the side effects with that of the hormone replacement therapies.

Types

1.Combination Oral Contraceptives

These compounds mostly contains an estrogen with a progestin.These combination have the benefit of reducing the side effects of both estrogens and progestins to a minimum and giving about of 99.9% increase in benefits.

The estrogens used are commonly ethynyl estradiol and mestranol. Among this ethynylestradiol is the most frequently used.

The progestins used are mostly 19 nor progestins(nor,means methyl)

The side effects of the progestins are depending on their androgenic.estrogenic and their anti-estrogenic activities.

Desogestrel and Norgesimate are the most recently developed progestins and have less side effects than the other 19 nor compounds.

These compounds are available as three phasic preparations as :- 1)Monophasic acting on any one of the three phases of the cycle.Comes in 21 days packings.

Contains equal quatities of esrogens and progestins are presnt in each pill which is taken 1 tablet daily for 21 days with a 7 days pill free period.Excempted by some packings which contains 28 pills with the 7 day pills contains no active ingredients.

Examples of Monophasics

1.Ethynylestradiol /Norethindrone combinations contains ethynylestradiol ranges from 0.020 to 0.050mg;   norethindrone acetate as progestin in various amounts ranges from 0.4 to 1.5 mg according to the brands

2.Ethynylestradiol /Levonorgestrel combination contains levonorgestrel 0.15 mg

3.Ethynylestradiol / Norgestrel contains norgestrel 0.3 and 0.5 in different brands

4.EthynylestrEthynylestradiolne diacetate combination contains the ethynodione diacetate 1 mg

5.Mestranol /Norethindrone combinations contains norethindrone 1 mg.

6.Ethynylestradiol / Desogesrel combinations contains desogesrel 0.15 mg.

7.Ethynylestradiol / Norgestimate combinations contains norgestimate 0.25 and 0.5 mg

2.Biphasics are acting on any two of the menstrua phases.They provide two different pills contains variying amount of active ingredients to be taken at different times during he 21 day cycle.This reduces the total amount steroids administered and thereby reduces their side effects.The amount variations of the steroids closely approximate the variations of steroids secreted in phases.For example generally the ratio of estrogen to progeserone higher in luteal phase and hence the amount of progestins can be reduced conveniently.These methods are developed in late 1980.

Examples of Biphasics

1.Ethynylestradiol / Norethindrone combinations contains 0.035 mg/5 mg in 10 tablets and 0.035 mg/1mg in 11 tablets in the brand NELOVA 10/11 and 0.035mg/0.5mg in 7tablets and 0.35mg/1mg in 14 tablets.in the brand JENSET-28

Triphasic these preparetions are acting on all three phases similar to biphasic their formula provides the amount of steroids according to the occuring during the phases.

Examples of the Triphasics

1.Ethynylestradiol/Norethindrone combination contains in all preparations the ratio of  ethynylestradiol  is 0.035mg  to the ratio of the norethindrone ranges from 0.5,0.75 and 1 mg in 7,7,7 tablets in one pack respectively according to the three phases to be taken as in ORTHONOVUM 7,7,7 

2.Ethynylestradiol/Norgestimate combination contains the amount of esradiol is 0.035mg to the ratio to norgestimate 0.18,0.215,0.25mg in 7,7,7 tablets per pack as in ORTHO-TRYCYCLIN
Remember that any pills which contains >50 microgram of estrogen is known as high dosed and if it contains <50 microgram is considered as low dosed.The lower limit is =20mic.gm.

2.Progestin Only Conraceptives

These combination has been deviced for particularly to whom estrogens are contra indicated like heart patients with high blood pressure and thrombo embolic diseases and breast cancer  etc.

Eventhough they are less efficacious they are widely used.

These agents block ovulations but less consistantly than combination tablets,suggesting that the they have some other additional mechanisms.

Preparation include the minipill  or the oral preparations of low dose progestins.These has to be taken daily without interrution;subdermal implants of 216 norgestrel as in NORPLANT is available for slow release and for a prolonged duration (for 5 years)

An Intra Uterine Device (Progestasert) that releases low amount of progestin locally is available to be used on yearly basis.

Examples of Progesin Only Contraceptives

Norethindrone as 0.35 mg is available for oral use as in MICRONOR AND NOR-QD

Norgesrel as 0.075 available as in OVERETTE

Postcoital Contraceptives  

These are available for preventing pregnancy decided on an emergency situation within 72 hours afer an unprotected coitus or intercourse.

1.Ethynylesradiol 100 micro gram combined with 1 mg Norgesrel to be taken twice 12 hour apart but initiated within 72 hours afer intercourse.

2.Ethynylestradiol alone in a dose of 2.5mg twice daily for 5 days initiated within 72 hours of the intercourse.

3.Conjugated estrogens 30 mg daily for 5 days.started within 72 hrs ater coitus.

4.Estrone with a dose of 5 mg three times daily for 5 days initiated within 72 hrs afer the coitus

5.Diethylstilbestrol 25 mg twice daily for 5 days but this regimen is largely reduced because of its side effects.

Among all the above the laest regimen successfully employed is the estradiol- norgestrel combination which is low dosed and more effective and safe provided that the regimen should be initiated within 72 hrs ater the intercourse.

The mechanism is unclear but beleived to be the delay in tubal transportation or development of endometrium hostile to implantation.

These high doses of estrogens frequently causes side effects such as

1.Head aches

2.Dizziness

3.Nausea

4.Vomiting

Because of the frequency and severity the above side effects Post Coital Contraceptives are in appropriate in many situations

Mechanisms of Actions

1.Combination Oral Contraceptives

These are mainly act by preventing ovulation by suppressing FSH and LH.

2.Progestin Only Preparations

Block ovulation similar to combination pills but less efficacious.These are largely acting on hypothalamus-anterior pituitary axis and suppressing Gonadotropin Releasing Hormone pulses.Also thickening of cervix to prevent the entry of sperm,and endometrial alteration to hostile the implantation of the ovum into the uterus are also the action of these preparations to avoid pregnancy.3
In general the women if she take the pill without forgot daily the she had the contraceptive protection well . 

Toxicities of Oral Hormonal Contraceptives

1.Formations of Blood Clots

2.Increased risks of Breast Cancer but this is questionable as convincing reports are suggesting that these compounds are reducing the incidences of endometrial and breast cancers especially by combination oral preparations.

3.Breast tenderness.

4.Headache

5.Gallstones

6.Acne

7.Weight gain.

8.Irregular,unpredictable breakthrough bleeding which leads to amenorrhea after 1 year use.(Typical to progestin alone contraceptives)
9.Visual problems
10.Non cancerous liver tumor

Contraindications

1.Pregnancy

2.History of Thrombo embolism 

3.Coronary Artery Disease like Angina,and MI

4.Central vascular disease

5.Congenital Hyperlipidemia
6.Breast or endometrial cancer
Drug Interactions
1.Contraceptive pills and smoking are disasterous as nicotine intracts with the hormones so seriouly.
2.Anti convulsants such as phenytoin (Dilantin),barbiturates and rifampin are all make the pill less potent 
3.Antibiotics such as Penicillins,tetracyclins,doxycyclins,and antifungal griseofulvin also will eliminate the contraceptive hormones very fast from our body and the pills ineffective.
The oralcontraceptives does not give any protections against sexually transmitted infections.

LONG ACTING CONTRACEPTIVE HORMONES

These methods are giving a convenience and no need to rely on daily doses of the pill without forgot

Medroxyprogesterone acetate is available in ijection form  by the trade name Depo-Provera and can give a 4 years contraceptive protection for a woman.The injection site should not be rubbed and massaged to keep the absorption to delay inorder to prolong the effect.
Breast cancer is more common in youngers below 27 years and less common in women above 35 years.
Contraception can easily be reversed after withdrawal of the drug in lean body than a fatty woman

 

 

 

 

 

WOMEN GYNACOLOGY-PART-VI-PROGESTINS

PROGESTINS-THE HORMONES OF PREGNANCY

Progestins are a group of steroidal female sex hormones mostly synthetic.The only naturally occuring progestin is the Progesterone which is the base for these synthetic progestins.Unlike estrogens this progesterone is  secreted during the gestational periods only that means the period from which a fully developed ovum detached from the overy and waiting for a sperm to fertilize it and upto the end of either the menstural cycle if no fertilization happen or upto the end of the pregnancy period if fertilization happened.The hormone progesterone is secreted from the yellow gland Corpus Luteum the gland which is temporarily formed at the gap from which the matured ovum detached from the ovary.

Progesterone the hormone of the pregnancy is controlling both the anterior pituitary-ovary axis and as well as the hypothalamus- anterior pituitary axis during the gestational period by a feed back mechanism to protect the fetus by preventing further maturing of the ovarian follicles.At the domination of progesterone at the set plasma limit during the gestational period there are no further secretions of FSH but, increases the LH pulsative sectretions from the anterior pituitary.The GRH secretions from the hypothalamus also decreased similar to FSH by progesterone While estradiol the main estrogen is controlling only the hypothalamus- anterior pituitary- axis and thus prevent the secretions of FSH and not of LH from the anterior pituitary by feed backchanism for all the times if its plasma level is raised to certain limits.

Once the ovum is fertilized the implantation takes place in one week.A hormone called human chorionic gonadotropin (HCG) is secreted from the a special layer within the uterus known as  trophoblast to keep the carpus luteum to be sustained and functional for some time upto the trophoblast itself becomes a fully developed placenta..This hormone is largely excreted by the kidneys mostly in the morning hours.Detection of this hormone in the urine by a specialised home kit test can confirm Pregnancy.

After several weeks of implantation placenta begins to develop.As a fully developed placenta can sufficiently produce progesteron and estrogen with collaberation of fetal adrenal glands and thereafter the corpus luteum begins to fade as its function is not further required and the secretion of CGH too will fade to be secreted further.

The amount of secretions of progesterone is varying as a few milligram per day at the beginning of follicular phase of the cycle followed by increasing upto 10 to 20 milligram during the luteal phase and further increases to several hundred milligrams during the later parts of the pregnancy period.

In the luteal phase progesterone act on the endometrium produced by the estrogens and decrease its further proliferation by estrogen,and develop a secondary endometrium as a luxury cusion for the convenience of the fertilized egg.

In case if there is no fertilization happened the secretions of progesterone and its domination decreased and the corpus luteum begins to fade at the end of the cycle and the domination of estrogen cause shedding of the secondary endometrium as a waste and excreted as menses at the end of the cycle.

At normal pregnancy period progesterone also act on the cervix and make it into thick and secretions to be more viscid inorder to prevent further entry of sperms through.This mechanism is more beneficiary for the use of synthetic progesterone like Norgestrel as a best oral contraceptives used alone or in combinations with estrogens.This we will discuss later in detail by the following posts.

Progeserone also modify the estrogen controlled matured vaginal epithelium in order to make it convenient and more elastic for delivering the baby 

Progeserone is very important in maintaining pregnancy.During pregnancy it protect the fetus by preventing contractions of the uterus and further mensturation.

During the pregnancy period progesterone along with estrogen acting on the mammary glands and proliferate it for milk production.But at the beginning of the lactating period the actions and secretions of progesterone and estrogen becomes nill.

WOMEN GYNACOLOGY-PART-IV-ESTROGEN OVER ACTIVITY-TREATMENTS

ANTIESTROGEN DRUGS

When secretions of estrogens are above the normal by the over activities of the ovaries the condition is known as hypergonadism of women.This condition may be natural or induced by careless administration of estrogens.In natural or provided hypergonadism the cause may be due to the active overstimulation of the ovaries by pituitary FSH and LH or passively by the hypothalamus stimulation of anterior pituitary by its hormone Gonadoropins releasing Hormones.
Either the conditions the over activities of estrogens cause so many problems in women.

Symptoms

1.Over secretions of estrogen will stop further secretions of FSH and LH by feed back mechanism which inturn block the development and maturity of the follicles leads to infertility.

2.Breast tenderness and cancer

3.Endomerial tenderness and cancer

4.Androgenic defeciency

5.Deep Venous Thrombosis(DVT)

6.Pulmonary Embolism (PE)

7.Changes in lipid and carbohydrate metabolism can cause or enhance hypertriglyceridemia and Diabetes Mellitus

8.Hypertension

9.Gall bladder disease

10.GI distress

11.Migrain

12.Mood disturbances 

Over activities of estrogens are 90% by misuse of estrogen intake mostly by contraceptives or other estrogen therapies like post 

menopausal hormone replacement therapies.

Estrogens are highly carcinogenic and can cause cancers in kidney bone and male sex organs.

Intake of estrogen like Diethyl Stibestreol(DE S) by a pregnant women during the first trmester can cause viginal and cervical cancer.This is is because the fetus cannot metabolize the DES and send it back to mother through the placenta which leads to the accumulation of the drug on her parts.Hence esrogens should be discouraged to take during pregnancy.

Administration of estrogens to post menopausal women as a hormonal replacement therapy may cause endometrial cancer in uterus.But the carcinoma can be cured by discontinuation of the therapy for several years.Hence estrogens should be administered to these patients in low dosages and in cyclic manners.

Although estrogens are having some favourable effects .on lipid metabolism such as lowering LDL,and elevating HDL but they may increase triglyceride levels

On gallbladder estrogens will increase cholesterol level dangerously to cause gallstones and other defects.

Fortunately in modern technics dose deviced for the hormon replacement therapy for post menopausal women are highly safe and in these dosages the incidences of hypertension,heart disease,stroke and thrombosis like DVT and PE are minimised.

Nausea and vomiting can be minimised by taking estrogens with food just before sleep. 

Treatments By Antiestrogens

1.Tamoxifen (Nolvadex)

It is a nonsteroidal anti estrogenic drug that competitively inhibit estrogens by binding to its receptors.

It is used for the treatment of breast cancers in postmenopausal women who receives hormonal replacement therapy.

Side Effects are hotflashes,nausea and vomiting

2.Chlomiphene (Clomid)

Its main action is by partially stimulating the estrogen receptors and thereby preventing the normal estrogenic feed back inhibition of anterior pituitary.There are sufficient secretions of FSH and LH by the pituitary which subsquently stimulates ovulation.

Its main use is to treat infertility.

Side effects are hot flashes,ovarian hyperplasia,Multiple simultaneous births,sight defects.

WOMEN GYNACOLOGY-PART III- FEMALE HYPOGONADISM-TREATMENTS

FEMALE OVARY DEFECTS-INFERTILITY-TREAMENTS-I

Female hypogonadism is a major cause for infertility.This can be a birth defect and it may be a major defect for a female baby.It will be a cause not only for female infertility but also for many physiological defects when the child grows.

In several conditions from the birth,or somewhere in a growing age by genetics or by an accident,the female parts mainly ovaries do not develop and puberty the age at which the child begins to feel as she is a woman does not occur 

Turner's syndrom is a condition in which the overies not formed properly and there is a dysgenesis of ovary the growth of the child stops to make the child to appear like a dwarf.
Estrogens such as estradiol orally or by injections in apporopriate preparations are used to treat the ovarian dysfunctions and to bring the puberty.
Androgens and growth hormone should be used in an appropriate manner to treat the dwarfism.
The symptoms of puberty replicates,the genital structures grow into normal,and the body assumes the normal feminine contour.
Hypopituitarism,the deficiency of anterior pituitary also cause ovarian dysfunction in the child hood.
Thyroid and adrenal cortex deficiencies,may also be a cause for ovarian underdevelopment.The treatment regimen should be the replacement therapies of the appropriate hormones of deficiency.
But in all the cases estrogens should be included to treat the sexual under development.
Administration of growth hormone will bring back the normal adult stature.
Estrogen along with androgen given at normal puberty age can induce a shorter growth.
Dysfunctional uterine bleeding and dysmenorrhea has been treated in earliar days by estrogens alone or in combinations with progesterone as in oral contraceptives.
Girls suffering from unwanted pimples and acne has been treated with oral contraceptives which contains estrogen combination with progesterone.The androgens produced by the ovaries,which causes the acne would be suppressed by estrogens.Also the same treatment can be used to treat hirsutism a condition in which unwanted hair growth like mustache and beard in women.
Estrogen now clinically Used
1.Estradiol(Estrace)
2.Conjugated estrogens (Premarin)
3.Ethinyl estradiol (Estinyl)
4.Quinestrol
Clinical Uses
1.Hypogonadism,under activities of ovaries
2.As Oralcontraceptives
3.Hormon replacement therapy. 
Route of administration Transdermally,intramuscularly and orally
Side effects
1.Post menopausal bleedings
2.Endomerial hyperplasia
3.Breast cancer
4.Cholestasis
5.Prolonged use may cause High Blood Pressure,Thromboembolism,liver cancer.
Estrogens should not be used in the following events:-
1.Breast cancer
2.Pregnancy
3.Liver disease
4.History of thrombophlebities.