But what exactly is Premarin? Premarin is a mixture of conjugated equineestrogens obtained exclusively from natural sources, occurring as the sodiumsalts of water-soluble estrogen sulfates blended to represent the averagecomposition of material derived from pregnant mares? urine. It is a mixture of sodiumestrone sulfate and sodium equilin sulfate. It contains as concomitantcomponents, as sodium sulfate conjugates, 17 ?-dihydroequilin, 17 ?-estradiol,and 17 ?-dihydroequilin.

Now, what is estrogen? Estrogen is hormone whose secretion starts from thegraffian follicle [which is present in the ovaries] under the influence ofFollicle Stimulating Hormone [FSH]and concentration in blood rises gradually during follicular phase of themenstrual cycle. Due to the modest Follicle Stimulating Hormone [FSH] surge, estrogens further rise transiently.After ovulation, corpus luteum continues to secrete estrogens till about twodays before menstruation. Estrogens exercise feed back inhibition of FollicleStimulating Hormone-FSH [alsoLeutinizing Hormone at higher levels] by direct action on the pituitary glandas well as through hypothalamus. In post menopausal women, there is a sharpdecline in estrogen. Thus sympathetic compounds of estrogen are useful in thetreatment of post menopausal deficiency states particularly when active ovarieshave been removed surgically and abrupt hormonal withdrawal is there.

In other words what we mean to say is that- Endogenous estrogens are largelyresponsible for the development and maintenance of secondary sexualcharacteristics and the female reproductive system. Estradiol is the principalintracellular human estrogen and is substantially more potent than itsmetabolites, estrone and estriol, at the receptor level. The primary source ofestrogen in normally cycling adult women is the ovarian follicle, whichsecretes 70 to 500 micrograms of estradiol daily, depending on the phase of themenstrual cycle. Post menopause, most endogenous estrogen is produced byconversion of androstenedione, secreted by the adrenal cortex, to estrone byperipheral tissues. Estrogens act through binding to nuclear receptors inestrogen-responsive tissues. Circulating estrogens modulate the pituitarysecretion of the gonadotropins, luteinizing hormone (LH) and folliclestimulating hormone (FSH) througha negative feedback mechanism. Estrogens act to reduce the elevated levels ofthese gonadotropins seen in postmenopausal women.

By now we have understood Premarin/Estrogen. Now let us discuss what we meanby post menopausal syndrome [PMS] Post- menopausal syndrome:

Menarche: the age at which a female starts having menstrual cycles. This isusually around 11-13 years. Menopause: the age at which a female ceases to haveher menstrual cycles. This is usually around 45 years. Post-menopause:Postmenopausal is defined formally as the time after which a woman hasexperienced twelve (12) consecutive months of amenorrhea (lack of menstruation)without a period.

Now, why do females suffer from post-menopausal syndrome?

Menopause and post menopause is associated with rapidly changing levels ofnatural hormones, hence the body tries to adapt to these changes. The effectsseen are however very variable and each woman respond in a very different wayto these changes. Let me add it right here that it is no rule that each femalesuffers from Post- menopausal syndrome. Also that some effects of Post-menopausal syndrome which may be due to decreased serum estrogen levels likeskin drying and vaginal atrophy may remain lifetime while many of the effectscaused by extreme changes in hormone levels like mood changes or hot flusheswould normally disappear or decrease in severity.[transition phase] Post-menopausal syndrome is characterized by - extreme fatigue - hot flashes,palpitations - sleep disturbances - dryness along with itching of vagina -urgency of urination - joint pain - risk of osteoporosis - formication, asensation rather like pins and needles, more specifically like ants crawling onor under the skin - breast atrophy - mood disturbances - depression - anxiety -dyspareunia or painful intercourse - decreased libido

Indications: - Post- menopausal syndrome - Senile vaginitis - Delayedpuberty in girls - Post menopausal osteoporosis 0.625 mg daily for 25 daysfollowed by a break of 5 days - Contraceptive - Dysmenorrhoea - Acne -Hirsuitism - Functional uterine bleeding - Suppression of lactation - Prostatecancer.1.25 mg to 2.5 mg three times daily. Palliative purposes only - Breastcancer. 10 mg three times daily for a period of at least three months.Palliative purposes only. - Female hypogonadism'0.3 mg to 0.625 mg daily,administered cyclically. Meaning for 3 weeks followed by a break of 1 week.

Above all the most important indication is Post- menopausal syndrome.

DOSAGE AND ADMINISTRATION Whenestrogen is prescribed for a postmenopausal woman with a uterus, progestinshould also be initiated to reduce the risk of endometrial cancer. A womanwithout a uterus does not need progestin. Use of estrogen, alone or incombination with a progestin, should be limited to the shortest durationconsistent with treatment goals and risks for the individual woman. Patientsshould be re-evaluated periodically as clinically appropriate, 3 or 6 monthlyintervals to determine if treatment is still necessary For women who have auterus, adequate diagnostic measures, such as endometrial sampling, whenindicated, should be undertaken to rule out malignancy in cases of undiagnosedpersistent or recurring abnormal vaginal bleeding.

Contraindications: - pregnancy - lactation - undiagnosed vaginal bleeding -Cardiovascular or cerebrovascular disorders like thrombophlebitis orthromboembolic processes. - Severe hepatic impairment - Hypertension - Herpesgestationis - Rotor syndrome - Dublin Johnson syndrome - Porphyria -Endometrial hyperplasia - Hyperlipoproteinemia - Suspected estrogen dependentneoplasia tumors - Premarin Tablets should not be used in patients with knownhypersensitivity to their ingredients ? Estrogens increase the chances ofgetting uterine/endometrial cancer Any unusual vaginal bleeding while usingPremarin should be brought to the notice of the doctor.Vaginal bleeding aftermenopause could be a warning sign of uterine cancer. ? Estrogens should not beused with or without progestins to prevent heart disease, heart attacks, strokes,or dementia. Using estrogens with or without progestins may increase thechances of getting heart attacks, strokes, breast cancer, and blood clots.Using estrogens, with or without progestins, may also increase the risk ofdementia. Hence the patient should be made fully aware of these issues beforestarting with Premarin Additional adverse effects seen with Premarin accordingto the FDA: - Changes in vaginal bleeding pattern and abnormal withdrawalbleeding or flow; breakthrough bleeding or spotting - Change in amount ofcervical secretion - Increase in size of uterine leiomyomata - Vaginitis,including vaginal candidiasis. - Changes in vaginal bleeding pattern andabnormal withdrawal bleeding or flow; breakthrough bleeding, spotting. - BreastTenderness, enlargement, pain, discharge, and galactorrhea. - Pulmonaryembolism. - Myocardial infarction. - Increased incidence of gallbladderdisease. - Chloasma or melasma that may persist when drug is discontinued. -Exacerbation of epilepsy.

Special precautions: - epilepsy - migraine - bronchial asthma - cardiacdisease - renal disease - discontinue if cancer progression or hypercalcemiaoccur - Premarin may cause salt and water retention, chronic mastitis [breast],abnormal mammograms - Impending major surgeries.

Laboratory Tests Premarin administration should be guided by clinicalresponse at the lowest dose for the treatment of postmenopausal moderate tosevere vasomotor symptoms and moderate to severe symptoms of postmenopausalvulvar and vaginal atrophy. Laboratory parameters may be useful in guidingdosage for the treatment of hypoestrogenism due to hypogonadism, castration andprimary ovarian failure.

Side effects: - suppression of libido - gynecomastia and feminization inmales - uterine cancer - breast cancer - benign hepatomas - Fusion of epiphysisof growing bones and this may lead to reduction of adult stature when given tochildren.

However Premarin has also courted controversy from the animal rightsactivists. Animal rights activists claim that animal husbandry and urinecollection methods used in Premarin's production cause undue stress andsuffering to the mares involved. Moreover there could be an overabundance ofpoorly bred foals produced by Pregnant Mare Urine (PMU)farms each year; these foals are often doomed to slaughter unless animal rescuegroups can get them to safety. Efforts are also made to rescue retired mares inlieu of their being sent to slaughter.