Premarin conjugated estrogen
Premarin [conjugated estrogen] manufactured by Wyeth Pharmaceuticals, is been marketed commercially since 1942. It is primarily used in treating post menopausal symptoms.
But what exactly is Premarin?
Premarin is a mixture of conjugated equine estrogens obtained exclusively from natural sources, occurring as the sodium salts of water-soluble estrogen sulfates blended to represent the average composition of material derived from pregnant mares’ urine. It is a mixture of sodium estrone sulfate and sodium equilin sulfate. It contains as concomitant components, as sodium sulfate conjugates, 17 -dihydroequilin.-estradiol, and 17 -dihydroequilin, 17
Now, what is estrogen?
Estrogen is hormone whose secretion starts from the graffian follicle [which is present in the ovaries] under the influence of Follicle Stimulating Hormone [FSH] and concentration in blood rises gradually during follicular phase of the menstrual cycle. Due to the modest Follicle Stimulating Hormone [FSH] surge, estrogens further rise transiently. After ovulation, corpus luteum continues to secrete estrogens till about two days before menstruation. Estrogens exercise feed back inhibition of Follicle Stimulating Hormone-FSH [also Leutinizing Hormone at higher levels] by direct action on the pituitary gland as well as through hypothalamus. In post menopausal women, there is a sharp decline in estrogen. Thus sympathetic compounds of estrogen are useful in the treatment of post menopausal deficiency states particularly when active ovaries have been removed surgically and abrupt hormonal withdrawal is there.
In other words what we mean to say is that-
Endogenous estrogens are largely responsible for the development and maintenance of secondary sexual characteristics and the female reproductive system. Estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level.
The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 micrograms of estradiol daily, depending on the phase of the menstrual cycle.
Post menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these gonadotropins seen in postmenopausal women.
By now we have understood Premarin/Estrogen. Now let us discuss what we mean by post menopausal syndrome [PMS]
Post- menopausal syndrome:
Menarche: the age at which a female starts having menstrual cycles. This is usually around 11-13 years.
Menopause: the age at which a female ceases to have her menstrual cycles. This is usually around 45 years.
Post-menopause: Postmenopausal is defined formally as the time after which a woman has experienced 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 of natural hormones, hence the body tries to adapt to these changes.
The effects seen are however very variable and each woman respond in a very different way to these changes. Let me add it right here that it is no rule that each female suffers from Post- menopausal syndrome. Also that some effects of Post- menopausal syndrome which may be due to decreased serum estrogen levels like skin drying and vaginal atrophy may remain lifetime while many of the effects caused by extreme changes in hormone levels like mood changes or hot flushes would 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, a sensation rather like pins and needles, more specifically like ants crawling on or under the skin
- breast atrophy
- mood disturbances
- dyspareunia or painful intercourse
- decreased libido
- Post- menopausal syndrome
- Senile vaginitis
- Delayed puberty in girls
- Post menopausal osteoporosis 0.625 mg daily for 25 days followed by a break of 5 days
- Functional uterine bleeding
- Suppression of lactation
- Prostate cancer.1.25 mg to 2.5 mg three times daily. Palliative purposes only
- Breast cancer. 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
When estrogen is prescribed for a postmenopausal woman with a uterus, progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin. Use of estrogen, alone or in combination with a progestin, should be limited to the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be re-evaluated periodically as clinically appropriate, 3 or 6 monthly intervals to determine if treatment is still necessary For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.
- undiagnosed vaginal bleeding
- Cardiovascular or cerebrovascular disorders like thrombophlebitis or thromboembolic processes.
- Severe hepatic impairment
- Herpes gestationis
- Rotor syndrome
- Dublin Johnson syndrome
- Endometrial hyperplasia
- Suspected estrogen dependent neoplasia tumors
- Premarin Tablets should not be used in patients with known hypersensitivity to their ingredients
• Estrogens increase the chances of getting uterine/endometrial cancer
Any unusual vaginal bleeding while using Premarin should be brought to the notice of the doctor.Vaginal bleeding after menopause could be a warning sign of uterine cancer.
• Estrogens should not be used with or without progestins to prevent heart disease, heart attacks, strokes, or dementia.
Using estrogens with or without progestins may increase the chances of getting heart attacks, strokes, breast cancer, and blood clots. Using estrogens, with or without progestins, may also increase the risk of dementia. Hence the patient should be made fully aware of these issues before starting with Premarin
Additional adverse effects seen with Premarin according to the FDA:
- Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding or spotting
- Change in amount of cervical secretion
- Increase in size of uterine leiomyomata
- Vaginitis, including vaginal candidiasis.
- Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding, spotting.
- Breast Tenderness, enlargement, pain, discharge, and galactorrhea.
- Pulmonary embolism.
- Myocardial infarction.
- Increased incidence of gallbladder disease.
- Chloasma or melasma that may persist when drug is discontinued.
- Exacerbation of epilepsy.
- bronchial asthma
- cardiac disease
- renal disease
- discontinue if cancer progression or hypercalcemia occur
- Premarin may cause salt and water retention, chronic mastitis [breast], abnormal mammograms
- Impending major surgeries.
Premarin administration should be guided by clinical response at the lowest dose for the treatment of postmenopausal moderate to severe vasomotor symptoms and moderate to severe symptoms of postmenopausal vulvar and vaginal atrophy. Laboratory parameters may be useful in guiding dosage for the treatment of hypoestrogenism due to hypogonadism, castration and primary ovarian failure.
- suppression of libido
- gynecomastia and feminization in males
- uterine cancer
- breast cancer
- benign hepatomas
- Fusion of epiphysis of growing bones and this may lead to reduction of adult stature when given to children.
However Premarin has also courted controversy from the animal rights activists. Animal rights activists claim that animal husbandry and urine collection methods used in Premarin's production cause undue stress and suffering to the mares involved. Moreover there could be an overabundance of poorly bred foals produced by Pregnant Mare Urine (PMU) farms each year; these foals are often doomed to slaughter unless animal rescue groups can get them to safety. Efforts are also made to rescue retired mares in lieu of their being sent to slaughter.
Premarin® (conjugated estrogens tablets, USP)
Each oval purple tablet contains 2.5 mg, in bottles of 100 (NDC 0046-0865-81) and
1,000 (NDC 0046-0865-91).
Each oval yellow tablet contains 1.25 mg, in bottles of 100 (NDC 0046-0866-81);
1,000 (NDC 0046-0866-91); 5,000 (NDC 0046-0866-95); and Unit-Dose Packages of
100 (NDC 0046-0866-99).
Each oval white tablet contains 0.9 mg, in bottles of 100 (NDC 0046-0864-81).
Each oval maroon tablet contains 0.625 mg, in bottles of 100 (NDC 0046-0867-81);
1,000 (NDC 0046-0867-91); 5,000 (NDC 0046-0867-95); and Unit-Dose Packages of
100 (NDC 0046-0867-99).
Each oval green tablet contains 0.3 mg, in bottles of 100 (NDC 0046-0868-81) and
1,000 (NDC 0046-0868-91)
Samir is the author of
Premarin, Conjugated Estrogens
information located at
- Drug Today, July-September 2005 Edition, pg 660