Also indexed as: Cenestin, Conjugated Estrogens, Esterified
Estrogens, Estratab, Menest, Premarin
Conjugated estrogens and esterified estrogens are both combinations of estrogenic hormones
used to treat menopausal symptoms, to prevent
osteoporosis in postmenopausal women, and as
replacement therapy in other conditions of inadequate estrogen production. They are also used
to treat some people with advanced breast and prostate cancers. Conjugated estrogens are
extracted and purified from the urine of pregnant horses. A synthetic conjugated estrogen
product (Cenestin®) is also available, as are combination products.
Combinations of estrogens with other hormones are also available. For example,
Estratest® is a combination of
methyltestosterone and esterified estrogens. Premarin is a combination of estrogens and progestins.
The information in this article pertains to combined estrogens in general. The interactions
reported here may not apply to all the Also Indexed As terms. Talk to your doctor or
pharmacist if you are taking any of these drugs.
Summary of
Interactions with Vitamins, Herbs, and Foods
In some cases, an herb or supplement may appear in more than one category, which may seem
contradictory. For clarification, read the full article for details about the summarized
interactions.
 May Be Beneficial: Depletion or
interference—The medication may deplete or interfere with the absorption or
function of the nutrient. Taking these nutrients may help replenish them. |
Vitamin B6*
|
| May Be Beneficial: Supportive
interaction—Taking these supplements may support or otherwise help your medication
work better. |
Calcium
Ipriflavone*
Vitamin D* (increased bone density)
|
Avoid: Reduced drug absorption/bioavailability—Avoid these supplements
when taking this medication since the supplement may decrease the absorption and/or activity
of the medication in the body. |
Herbal sources of isoflavone supplements (red clover*, soy*)
|
|
Avoid: Adverse interaction—Avoid these supplements when taking this
medication because taking them together may cause undesirable or dangerous results. |
Tobacco
Vitamin D*
|
Check: Other—Before taking any of these supplements or eating any of
these foods with your medication, read this article in full for details. |
Magnesium
Zinc
|
| Side effect reduction/prevention |
None known
|
An asterisk (*) next to an item in the summary indicates that the
interaction is supported only by weak, fragmentary, and/or contradictory scientific
evidence.
Interactions with Dietary Supplements
Calcium
Two months of conjugated estrogen therapy in women with surgically induced menopause decreased
urinary calcium loss and increased serum vitamin
D levels.1 In a six-month placebo-controlled study of 21 women with
postmenopausal osteoporosis, conjugated estrogens increased both calcium absorption and
vitamin D blood levels.2
While estrogen may improve calcium absorption, it remains important for women taking
estrogen to maintain adequate calcium intake through diet and supplementation. Many doctors
recommend 800–1,200 mg of supplemental calcium in addition to the several hundred
milligrams found in a typical daily diet.
Ipriflavone
Ipriflavone, a synthetic variation of isoflavones found in soy, is available as a supplement. In a controlled
trial, ipriflavone (400 mg per day) plus conjugated estrogens increased vertebral bone
density, while calcium (500 mg per day) plus conjugated estrogens could not prevent a decrease
in bone density in postmenopausal women.3 Similarly, a double-blind trial found
ipriflavone (600 mg per day) plus conjugated estrogens and calcium (1 gram per day) increased
bone density, while calcium with or without conjugated estrogens could not prevent bone
loss.4 While low doses of estrogens can counteract some menopausal symptoms, higher
doses are required to prevent bone loss in postmenopausal women. However, the addition of
ipriflavone to low-dose estrogen therapy has been shown in a controlled trial to preserve bone
mass in postmenopausal women.5
Minerals
A preliminary trial found that osteoporotic postmenopausal women with elevated urinary zinc
and magnesium excretion experienced reduced losses of these minerals after being treated with
conjugated estrogens and
medroxyprogesterone.6 More research is needed to determine the significance of
this finding.
Vitamin
B6
A small preliminary trial found most women taking conjugated estrogens therapy without a
progestin to have lower levels or a deficiency of vitamin B6.7 Numerous studies
have found negative effects of oral
contraceptives (OCs) on vitamin B6 status,8 9 10 although
some studies suggest that vitamin B6 deficiency does not occur when low-dose OCs are
used.11 While OCs contain different forms of estrogen than conjugated estrogens,
there is a possibility of a similar problem when any form of estrogen is supplemented, but
more research is needed.
Vitamin
D
A controlled trial found two months of conjugated estrogens therapy in women with surgically
induced menopause increased blood levels of vitamin D and decreased urinary calcium loss.12 In a controlled study of
women with postmenopausal osteoporosis, conjugated estrogens therapy was associated with
increased blood levels of vitamin D and increased calcium absorption.13 While
conjugated estrogens appear to improve vitamin D metabolism, it remains important for women
taking such hormones to consume adequate levels of vitamin D through diet and supplements.
One controlled study showed that taking 300 IU of vitamin D per day with estradiol, an estrogen related to conjugated
estrogens, plus a progestin led to greater improvement in bone density compared with
estradiol/progestin alone.14 Further controlled studies are needed to determine
whether taking conjugated estrogens and vitamin D together might also increase bone strength
and prevent fractures. In contrast to the beneficial effects on bone, the study also revealed
that supplementing vitamin D together with estradiol/progestin tended to reduce beneficial HDL
cholesterol levels, unlike estradiol/progestin
alone. These undesirable results were confirmed by two additional studies.15
16
Additional research is needed to determine the degree to which supplemental vitamin D might
exert a supportive or adverse effect on the actions of conjugated estrogens. Until more
information is available, women taking hormone replacement therapy are advised to talk with a
physician before combining vitamin D with conjugated estrogens.
Interactions with Herbs
Isoflavones
Herbal sources of isoflavones, such as red
clover, may interfere with or even have an additive effect with conjugated
estrogens.17 Further studies are needed to establish the potential interaction of
isoflavone supplements from red clover and soy
with conjugated estrogens. Consult with your healthcare professional if you are currently
taking estrogen replacement therapy and wish to take a supplement high in isoflavones.
Interactions with Foods and Other Compounds
Tobacco
Conjugated estrogens therapy in postmenopausal women has been reported to decrease LDL
(“bad”) cholesterol levels and to
increase HDL (“good”) cholesterol levels. However, despite the positive changes in
blood levels of LDL and HDL cholesterol, there is evidence that conjugated estrogens do not
reduce the risk of heart disease.18
Nonetheless, smoking offsets the cholesterol changes induced by taking conjugated
estrogens,19 and this interference is likely to be detrimental. Women taking
conjugated estrogens who do not smoke should avoid starting, and those who do smoke should
talk with their doctor about quitting.
References:1. Lobo RA, Roy S, Shoupe D, et al. Estrogen and progestin effects on
urinary calcium and calciotropic hormones in surgically-induced postmenopausal women. Horm
Metab Res 1985;17:370–3.
2. Gallagher JC, Riggs BL, DeLuca HF. Effect of estrogen on calcium
absorption and serum vitamin D metabolites in postmenopausal osteoporosis. J Clin
Endocrinol Metab 1980;51:1359–64.
3. Gambacciani M, Ciaponi M, Cappagli B, et al. Effects of combined low
dose of the isoflavone derivative ipriflavone and estrogen replacement on bone mineral density
and metabolism in postmenopausal women. Maturitas 1997;28:75–81.
4. Melis GB, Paoletti AM, Bartolini R, et al. Ipriflavone and low doses
of estrogens in the prevention of bone mineral loss in climacterium. Bone Miner Oct
1992;19 suppl 1:S49–56.
5. Agnusdei D, Gennari C, Bufalino L. Prevention of early postmenopausal
bone loss using low doses of conjugated estrogens and the non-hormonal, bone-active drug
ipriflavone. Osteoporos Int 1995;5:462–6.
6. Herzberg M, Lusky A, Blonder J, et al. The effect of estrogen
replacement therapy on zinc in serum and urine. Obstet Gynecol
1996;87:1035–40.
7. Haspels AA, Bennink HJ, Schreurs WH. Disturbance of tryptophan
metabolism and its correction during oestrogen treatment in postmenopausal women.
Maturitas 1978;1:15–20.
8. Lubby AL, Brin M, Gordon M, et al. Vitamin B6 metabolism in users of
oral contraceptive agents. I. Abnormal urinary xanthurenic acid excretion and its correction
by pyridoxine. Am J Clin Nutr 1971;24:684–93.
9. Adams PW, Rose DP, Folkard J, et al. Effect of pyridoxine
hydrochloride (vitamin B6) upon depression associated with oral contraception. Lancet
1973;1:897–904.
10. Larsson-Cohn U. Oral contraceptives and vitamins: a review. Am J
Obstet Gynecol 1975;121:84–90 [review].
11. Massé PG, van den Berg H, Duguay C, et al. Early effect of a low
dose (30 mcg) ethinyl estradiol-containing Triphasil® on vitamin B6 status. Int J Vit
Nutr Res 1996;66:46–54.
12. Lobo RA, Roy S, Shoupe D, et al. Estrogen and progestin effects on
urinary calcium and calciotropic hormones in surgically-induced postmenopausal women. Horm
Metab Res 1985;17:370–3.
13. Gallagher JC, Riggs BL, DeLuca HF. Effect of estrogen on calcium
absorption and serum vitamin D metabolites in postmenopausal osteoporosis. J Clin
Endocrinol Metab 1980;51:1359–64.
14. Tuppurainen MT, Komulainen M, Kröger H, et al. Does vitamin D
strengthen the increase in femoral neck BMD in osteoporotic women treated with estrogen?
Osteoporosis Int 1998;7:32–8.
15. Myrup B, Hensen GF, McNair P. Cardiovascular risk factors during
estrogen-norethindrone and cholecalciferol treatment. Arch Intern Med
1992;152:2265–8.
16. Heikkinen A-M, Tuppurainen MT, Niskanen L, et al. Long-term vitamin
D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone
replacement therapy. Eur J Endocrinol 1997;137:495–502.
17. Collins BM, McLachlan JA, Arnold SF. The estrogenic and
antiestrogenic activities of phytochemicals with the human estrogen receptor expressed in
yeast. Steroids 1997;62:365–72.
18. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus
progestin for secondary prevention of coronary heart disease in postmenopausal women.
JAMA 1998;280:605–13.
19. Krauss RM, Perlman JA, Ray R, Petitti D. Effects of estrogen dose and
smoking on lipid and lipoprotein levels in postmenopausal women. Am J Obstet Gynecol
1988;158:1606–11.