The information on this site is intended to supplement and enhance, not replace, the advice of a physician who is familiar with your medical history. Decisions about your health should always be made ONLY after detailed conversation with your doctor.
Generic drug name:
ethinyl estradiol with norethindrone
(ETH in il es tra DYE ole with nor ETH in drone)
Brand name(s):
ACTIVELLA,
ALYACEN,
AMABELZ,
ARANELLE,
COMBIPATCH,
DASETTA,
FEMHRT
GENERIC:
available
FAMILY:
Hormone Combinations
Find the drug label by
searching at DailyMed.
Limited Use
[what does this mean?]
Generic drug name:
conjugated estrogens with medroxyprogesterone
(CON joo gay ted ESS troe jenz with me DROX ee proe)
Brand name(s):
PREMPHASE,
PREMPRO
GENERIC:
not available
FAMILY:
Hormone Combinations
Find the drug label by
searching at DailyMed.
Pregnancy and Breast-feeding Warnings [top]
PREGNANCY WARNING
Because of the potential for serious adverse effects to the fetus, these drugs should not be used by women with known or suspected pregnancy.
BREAST-FEEDING WARNING
Estrogens are excreted in breast milk and have caused adverse effects in nursing infants including jaundice and breast enlargement. If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completly weaned her child. These drugs may also decrease the amount and quality of breast milk. Because of the potential for adverse effects in nursing infants, you should not take these drugs while nursing.
Safety Warnings For This Drug [top]
FDA BLACK-BOX WARNING for conjugated estrogens with medroxyprogesterone (PREMPRO, PREMPHASE)
WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER, ENDOMETRIAL CANCER AND PROBABLE DEMENTIA
Cardiovascular Disorders and Probable Dementia
Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia.
The estrogen-plus-progestin substudy of the Women's Health Initiative (WHI) reported increased risks of deep vein thrombosis (blood clots in large veins, most often in the legs), pulmonary embolism (blood clots in the lungs), stroke and heart attack in postmenopausal women (50 to 79 years of age) during 5.6 years of daily treatment with conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) per day relative to placebo.
The WHI's 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 four years of daily treatment with conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
Breast Cancer
The estrogen-plus-progestin substudy of the WHI also demonstrated an increased risk of invasive breast cancer.
In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugated estrogens and medroxyprogesterone acetate.
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.
FDA BLACK-BOX WARNING
for ethinyl estradiol with norethindrone (FEMHRT)
WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER, ENDOMETRIAL CANCER AND PROBABLE DEMENTIA
Cardiovascular Disorders and Probable Dementia
Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia.
The estrogen-plus-progestin substudy of the Women’s Health Initiative (WHI) reported increased risks of deep vein thrombosis (blood clots in large veins, most often in the legs), pulmonary embolism (blood clots in the lungs), stroke and heart attack in postmenopausal women (50 to 79 years of age) during 5.6 years of daily treatment with conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) per day relative to placebo.
The WHI’s 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 four years of daily treatment with conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
Breast Cancer
The estrogen-plus-progestin substudy of the WHI also demonstrated an increased risk of invasive breast cancer. In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugated estrogens and medroxyprogesterone acetate.
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.
Beware of Compounding Pharmacists Selling "Bioidentical" Hormone Replacement Therapies, Claiming That They Are Safe
Pharmacy compound products are not approved by the FDA and their quality is questionable, as they are not produced in facilities meeting good manufacturing practice (GMP) guidelines.
Facts About This Drug [top]
These combination estrogen-with-progestin products are approved by the Food and Drug Administration (FDA) to manage the symptoms of menopause. These drugs also are approved to prevent osteoporosis. However, estrogens are no longer approved for the treatment of osteoporosis. Treatment solely for the prevention of postmenopausal osteoporosis should be considered only for women at significant risk of osteoporosis and for whom non-estrogen medications are not considered to be appropriate.[1],[2]
...These combination estrogen-with-progestin products are approved by the Food and Drug Administration (FDA) to manage the symptoms of menopause. These drugs also are approved to prevent osteoporosis. However, estrogens are no longer approved for the treatment of osteoporosis. Treatment solely for the prevention of postmenopausal osteoporosis should be considered only for women at significant risk of osteoporosis and for whom non-estrogen medications are not considered to be appropriate.[1],[2]
The mainstays for decreasing the risk of postmenopausal osteoporosis are weight-bearing exercise, adequate calcium and vitamin D intake and, when needed, treatment with drugs.
Postmenopausal women require an average of 1,500 milligrams per day of elemental calcium. Therefore, when not contraindicated, calcium supplementation may be helpful for women with suboptimal dietary intake. Vitamin D supplementation of 400-800 international units per day also may be required to ensure adequate daily intake in postmenopausal women.[1],[2]
The progestins medroxyprogesterone and norethindrone are added to the estrogen component of these products to reduce the risk of uterine cancer in women who have an intact uterus.
The Canadian Task Force on Preventive Health Care recommends "against the use of combined estrogen-progestin therapy and estrogen-only therapy for the primary prevention of chronic diseases in menopausal women." For the management of the symptoms of menopause, this Task Force recommends the following: "If the risks are acceptable to the woman and her physician, therapy of as short a duration a possible, and at as low a dose as possible, may be indicated."[3] We agree.
The North American Menopause Society (NAMS) has issued its position on the management of hot flashes in postmenopausal women. For mild hot flashes, lifestyle-related strategies such as keeping the core body temperature cool, participating in regular exercise and using paced respiration have shown some effectiveness without adverse effects.[4]
The NAMS found that, among nonprescription remedies, clinical trial results are insufficient to either support or refute the efficacy of soy foods and isoflavone supplements (soy or red clover), black cohosh or vitamin E for hot flashes. Single clinical trials have found no benefit for dong quai, evening primrose oil, ginseng, a Chinese herbal mixture, acupuncture or magnet therapy.[4]
Research published in 2005 in Obstetrics & Gynecology found that estrogen plus progestin therapy in postmenopausal women, known as hormone replacement therapy (HRT), increases the risk of urge and stress incontinence within four months of beginning treatment.
Because the risks of HRT outweigh its benefits for most uses, these products now have a black-box warning (see above) in their professional product labels. The FDA also has limited the approved uses of HRT to the short-term treatment of moderate-to-severe hot flashes associated with menopause. HRT is no longer approved for the long-term treatment of the symptoms of menopause. The FDA cautions prescribers that women with postmenopausal osteoporosis should use other products, such as alendronate (FOSAMAX), before resorting to HRT. In other words, HRT is the last choice for postmenopausal osteoporosis.[5]
Information from the Women’s Health Initiative trial showed that when postmenopausal women used a combination of estrogen and medroxyprogesterone hormone therapy, there was an increased risk of deep vein thrombosis (blood clots in large veins, most often in the legs), pulmonary embolism (blood clots in the lungs), stroke, heart attack, invasive breast cancer and probable dementia compared with women receiving a placebo.[6]
Another study published in JAMA reported that patients on hormone therapy were at an increased risk of ovarian cancer. [7]
The January 2014 issue of Worst Pills, Best Pills News reviewed the risks and benefits of HRT. Two major clinical trials published in 2002 and 2004 revealed a high incidence of breast cancer and stroke with long-term use of HRT. Although HRT use is now much lower than either before or after the 2002 study, the number of prescriptions for HRT remains troublingly high and may be increasing. HRT should therefore be used at the lowest dose and for the shortest duration necessary to meet treatment goals. To read more, see “Hormone Replacement Therapy: Use at the Lowest Dose for the Shortest Amount of Time.”
In 2019, Lancet published a study showing that the longer the use of all types of hormone therapy (except vaginal estrogen, such as estradiol vaginal cream [ESTRACE]), the higher the risk of invasive breast cancer (breast cancer that spreads into surrounding breast tissue). It also found that combination hormone therapy is associated with a higher breast cancer risk than estrogen-only therapy.[8]
In 2020, JAMA published an article warning that the use of combination estrogen and medroxyprogesterone increased the risk of breast cancer but made no difference in breast cancer death in women with a uterus compared with use of a placebo. Use of estrogen alone had a lower risk of breast cancer and breast cancer death in women who had a hysterectomy compared withuse of a placebo.[9]
Before You Use This Drug [top]
Do not use if you have or have had:
Tell your doctor if you have or have had:
When You Use This Drug [top]
How to Use This Drug [top]
Interactions with Other Drugs [top]
The following drugs, biologics (e.g., vaccines, therapeutic antibodies), or foods are listed in Evaluations of Drug Interactions 2003 as causing “highly clinically significant” or “clinically significant” interactions when used together with any of the drugs in this section. In some sections with multiple drugs, the interaction may have been reported for one but not all drugs in this section, but we include the interaction because the drugs in this section are similar to one another. We have also included potentially serious interactions listed in the drug’s FDA-approved professional package insert or in published medical journal articles. There may be other drugs, especially those in the families of drugs listed below, that also will react with this drug to cause severe adverse effects. Make sure to tell your doctor and pharmacist the drugs you are taking and tell them if you are taking any of these interacting drugs:
EVISTA, nelfinavir, NORVIR, raloxifene, ritonavir, VIRACEPT.
Adverse Effects [top]
Call your doctor immediately if you experience:
Call your doctor if these symptoms continue:
Signs of overdose (ethinyl estradiol with norethindrone acetate):
If you suspect an overdose, call this number to contact your poison control center: (800) 222-1222.
Periodic Tests[top]
Ask your doctor which of these tests should be done periodically while you are taking this drug:
last reviewed October 31, 2023
Worst Pills, Best Pills is a project of Public Citizen's Health Research Group Group. As an independent, nonprofit organization, we take no corporate or government contributions and accept no advertising. Copyright © 2024 Public Citizen's Health Research Group. All rights reserved.
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