Estragyn (Esterified Estrogens) Vaginal Cream 0.1%

Esterified Estrogens, Estragyn/Menest

Description: Estrogen Derivative

“ALERT: US Boxed Warning

Endometrial cancer:

Estrogens increase the risk of endometrial cancer. Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of “natural” estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses.

Cardiovascular disease:

Estrogens with and without progestins should not be used for the prevention of cardiovascular disease. The Women’s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone (2.5 mg), relative to placebo.

Breast cancer:

The Women’s Health Initiative (WHI) study reported increased risks of invasive breast cancer in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone (2.5 mg) relative to placebo.

Dementia:

The Women’s Health Initiative Memory Study (WHIMS) a substudy of WHI, reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women or to women taking estrogen alone therapy.

Risk vs benefits:

Other doses of conjugated estrogens with medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.”

CSA NA – FDA Approved – REMS (N) – Can Ship

Esterified estrogens contain a mixture of estrogenic substances with the primary component being estrone.  Estrogen is a female sex hormone that supports the development and function of the female reproductive system, secondary sex characteristics and urogenital structures.  Estradiol is the principle female estrogen and inhibits the pituitary release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) thereby inhibiting ovulation through a negative feedback system. 

Esterified Estrogens, Estragyn/Menest is officially indicated for use in metastatic breast cancer, prostate cancer, estrogen replacement therapy in estrogen deficiency states, vasomotor symptoms associated with menopause, vulvar and vaginal atrophy associated with menopause.

Do not use in women with an increased risk of invasive breast cancer

Do not use in women to prevent or treat dementia

Do not use unopposed estrogen in women with a uterus

Do not use in women with endometriosis

Use with caution in women with pre-existing hypertriglyceridemia

Use with caution in women with ovarian cancer

Use with caution in women with retinal vascular thrombosis

Use with caution in asthma, carbohydrate intolerance, cardiovascular disease, fluid retention, hepatic dysfunction, hypoparathyroidism, migraines, porphyria, and system lupus erythematosus

Prostate Cancer
Esterified Estrogens, Estragyn/Menest: Take 1.25mg to 2.5mg three times daily.

Breast Cancer
Estragyn, Menest/Esterified Estrogen: Take 10mg three times daily. 

Estrogen Replacement Therapy due to Menopause

Esterified Estrogens, Estragyn/Menest: Take 2.5mg to 7.5mg daily in divided doses for 20 days followed by a 10-day rest period.  If bleeding does not occur by the end of the 10-day period, repeat the same dosing schedule; the number of courses to produce bleeding is dependent upon the responsiveness of the endometrium.  If bleeding occurs before the end of the 10-day period, begin an estrogen-progestin cyclic regimen of 2.5mg to 7.5mg daily in divided dose for 20 days; during the last 5 days of the estrogen therapy, take an oral progestin.

Vasomotor Symptoms Associated with Menopause
Esterified Estrogens, Estragyn/Menest: Take 1.25mg daily three weeks on and one week off cycle.  If menstrual bleeding has not occurred for > 2 months, cyclic administration can be started anytime.  If you start menstruating, cyclic administration is started on day 5 of the bleeding.

Vulvar and Vaginal Atrophy Associated with Menopause
Esterified Estrogens, Estragyn/Menest: Take 0.3mg to 1.25mg daily and adjust the dose based on the patient response.  Take in cyclic fashion, 3 weeks on followed by 1 week off.

*When treating symptoms of vulvar and vaginal atrophy, topical application of esterified estrogen should be considered.

How Do You Take Esterified Estrogens, Estragyn/Menest: You can take tablets with food or after a meal to reduce nausea.   You can apply topical applications at bedtime.  Take the medication exactly as prescribed by your doctor.  If you miss a dose, make sure to take it as soon as possible.  However, if it is almost time for your next dose, skip the missed dose and continue with your regular schedule.

Contact Your Doctor if You Ever Experience:  If you experience a sudden, intense, severe headache or chest pain; sudden loss of coordination; sudden loss of vision or speech disturbances; chest or calf pain; weakness in the extremities; sudden shortness of breath of pain with breathing (may indicate thromboembolic disorder); persistent or recurrent vaginal bleeding (may indicate endometrial cancer); edema; abdominal pain or jaundice (may indicate hepatitis or gallbladder disease).

The frequency of side effects is not well defined and some of the adverse reactions are dependent on the dosage form and combination therapy used:

>10%

Cardiovascular: Edema (10% to 13%)

Central Nervous System: Headache (9% to 50%), pain (6% to 13%), depression (1% to 11%), anxiety (4% to 10%)

Dermatologic: Skin rash (7% to 10%)

Endocrine and Metabolic: Weight gain (4% to 10%)

Gastrointestinal: Abdominal pain (6% to 16%)

Genitourinary: Mastalgia (5% to 35%), vaginal hemorrhage (33%), breast tenderness (3% to 17%), endometrium disease (15%), breakthrough bleeding (6% to 11%), abnormal bleeding (4% to 10%)

Infection: Infection (3% to 12%), fungal infection (3% to 10%)

Neuromuscular and Skeletal: Arthralgia (4% to 12%), back pain (3% to 11%)

Respiratory: Nasopharyngitis (4% to 20%), upper respiratory tract infection (6% to 17%), flu-like symptoms (8% to 13%), sinusitis (4% to 13%), sinus headache (9% to 11%)

Hormone Replacement Therapy
Hormone Replacement Therapy (HRT) refers to the use of an estrogen and a progestin in post-menopausal women.  In estrogen replacement therapy (ERT) only estrogen is administered.  It is critically important to include a progestin to reduce an estrogen induced risk of endometrial hyperplasia in women.  Estrogen replacement therapy is only used in women who have had a hysterectomy and thus are not at risk for these problems.

Treatment of Menopausal Symptoms
HRT effectively relieves or eliminates vasomotor symptoms (hot flushes, sweating), sleep disturbance and poor concentration in a dose-dependent manner.

Treatment of Urogenital Problems
HRT effectively treats post-menopausal vaginal dryness and dyspareunia with vaginal therapy being most effective.  Furthermore, there is evidence supporting the usage of vaginal estrogens in reducing the frequency of post-menopausal urinary tract infections.

Prevention and Treatment of Osteoporosis
HRT (with or without a progestin) taken for a period of at least 5 to 10 years is estimated to reduce the risk of osteoporosis-related hip fractures by at least 25%, wrist fractures by 25% to 75% and vertebral fractures by at least 50%; the reduction in risk is directly related to the duration of use.  For optimal protection against fracture, HRT should be started within 3 to 5 years after the last menstrual period.  

Other Uses: There is limited evidence that HRT may help minimize weight gain, prevent skin wrinkling and dryness which typically occur following menopause.

Place in Therapy
Current clinical research suggests that HRT should not be used routinely and/or long-term in post-menopausal women.  Those women who are likely to experience benefits from HRT should fully understand the fully the benefits along with the risks associated with HRT and agree to regular medical examinations. Only short-term therapy is recommended due to the risks of breast cancer, thromboembolism, and coronary heart disease.

Benefits Versus Risks Associated with HRT

Common Problems and Suggestions

General Dosage Considerations
Progestin must be included in HRT for women with an intact uterus to reduce the estrogenic-induced risk of endometrial hyperplasia and carcinoma.  A progestin is not needed if a woman has had a hysterectomy.  The progestin dosage depends on the estrogen dose.

Estrogen doses required to treat menopausal vasomotor symptoms should be titrated to individual response.  Younger women have been shown to need higher doses.  It is encouraged that women discontinue every three to six months to determine if estrogen is still needed.

Estrogen Dosing Considerations:
To Preserve Bone Mineralization and Prevent Bone Thinning

Oral Conjugated Estrogen: 0.625mg daily.

Oral Estradiol-17β: 1-2mg daily.

Estradiol-16β Transdermal Patch: 50mcg daily.

Continuous Estrogen Plus Progestin (Continuous Combined Regimen)
This regimen provide relief from menopausal symptoms while avoiding withdrawal bleeding.  It is designed to induce amenorrhea, however spotting can in the first 6 to 12 months on regimens of conjugated estrogens plus progestins.  Most women develop amenorrhea within 12 months.

1. Oral conjugated estrogen 0.3mg to 1.25mg daily plus oral medroxyprogesterone 2.5mg to 5mg or micronized progesterone 100mg daily.
2. Ethinyl estradiol 5mcg plus norethindrone 1mg daily.

Continuous Estrogen Plus Cyclic Progestin
This regimen provides relief from menopausal symptoms with regular withdrawal bleeding.  It may be tolerated than continuous progestin during the first year of menopause.

1. Oral conjugated estrogen 0.3mg to 1.25mg daily (or equivalent oral or transdermal) plus oral medroxyprogesterone 5mg to 10mg daily or micronized progesterone 200mg daily for 12-14 days per months.
2. Transdermal estradiol 50mcg daily for 2 weeks then combined with norethindrone 250mcg for 2 weeks.
3. Oral conjugated estrogen 0.3mg to 1.25mg daily (or equivalent oral or transdermal) continuously with medroxyprogesterone 10mg daily for 14 days every 3 months.  With this regimen, withdrawal bleeding occurs only once every 3 months, however a minor percentage of women may have spotting and withdrawal bleeding.  

Cyclic Estrogen
Menopausal vasomotor symptoms may return during estrogen-free days.

Oral conjugated estrogen 0.3mg to 1.25mg daily (or equivalent oral or transdermal) for 21 to 25 days each month with medroxyprogesterone 10mg daily for the last 12-14 days of every month.

Progestin Only
Used if estrogen is contraindicated.

1. Oral medroxyprogesterone 10mg to 20mg daily on response.

Vaginal Preparations
Vaginal preparations in the form of creams, gels, ovules only treat urogenital symptoms.  Vaginal preparations can be applied daily until symptoms resolve and can be used as a maintenance therapy with creams/gels/ovules being used twice weekly or a vaginal ring. 

Available Dosage Forms