Oestrogens (Combined)

Also indexed as: Cenestin, Conjugated Oestrogens, Esterified Oestrogens, Estratab, Menest, Premarin

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Conjugated oestrogens and esterified oestrogens are both combinations of oestrogenic hormones used to treat menopausal symptoms, to prevent osteoporosis in postmenopausal women, and as replacement therapy in other conditions of inadequate oestrogen production. They are also used to treat some people with advanced breast and prostate cancers. Conjugated oestrogens are extracted and purified from the urine of pregnant horses. A synthetic conjugated oestrogen product (Cenestin®) is also available, as are combination products.

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Combinations of oestrogens with other hormones are also available. For example, Estratest® is a combination of methyltestosterone and esterified oestrogens. Premarin is a combination of oestrogens and progestins.

The information in this article pertains to combined oestrogens in general. The interactions reported here may not apply to all the Also Indexed As terms. Talk to your doctor or chemist if you are taking any of these drugs.

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Summary of Interactions with Vitamins, Herbs, and Foods
In some cases, a 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.

Beneficial 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*
Beneficial 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 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*, soya*)
Avoid Avoid: Adverse interaction—Avoid these supplements when taking this medication because taking them together may cause undesirable or dangerous results.

Tobacco

Vitamin D*
Check 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
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An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

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Interactions with Dietary Supplements

Calcium
Two months of conjugated oestrogen 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 oestrogens increased both calcium absorption and vitamin D blood levels.2

While oestrogen may improve calcium absorption, it remains important for women taking oestrogen to maintain adequate calcium intake through diet and supplementation. Many doctors recommend 800–1,200 mg of supplemental calcium in addition to the a few hundred milligrams found in a typical daily diet.

Ipriflavone
Ipriflavone, a synthetic variation of isoflavones found in soya, is available as a supplement. In a controlled trial, ipriflavone (400 mg per day) plus conjugated oestrogens increased vertebral bone density, while calcium (500 mg per day) plus conjugated oestrogens 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 oestrogens and calcium (1 gram per day) increased bone density, while calcium with or without conjugated oestrogens could not prevent bone loss.4 While low doses of oestrogens can counteract some menopausal symptoms, higher doses are required to prevent bone loss in postmenopausal women. However, the addition of ipriflavone to low-dose oestrogen 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 oestrogens 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 oestrogens 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 oestrogen than conjugated oestrogens, there is a possibility of a similar problem when any form of oestrogen is supplemented, but more research is needed.

Vitamin D
A controlled trial found two months of conjugated oestrogens 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 oestrogens therapy was associated with increased blood levels of vitamin D and increased calcium absorption.13 While conjugated oestrogens 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 oestrogen related to conjugated oestrogens, 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 oestrogens 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 oestrogens. Until more information is available, women taking hormone replacement therapy are advised to talk with a physician before combining vitamin D with conjugated oestrogens.

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Interactions with Herbs

Isoflavones
Herbal sources of isoflavones, such as red clover, may interfere with or even have an additive effect with conjugated oestrogens.17 Further studies are needed to establish the potential interaction of isoflavone supplements from red clover and soya with conjugated oestrogens. Consult with your healthcare professional if you are currently taking oestrogen replacement therapy and wish to take a supplement high in isoflavones.

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Interactions with Foods and Other Compounds

Tobacco
Conjugated oestrogens 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 oestrogens do not reduce the risk of heart disease.18 Nonetheless, smoking offsets the cholesterol changes induced by taking conjugated oestrogens,19 and this interference is likely to be detrimental. Women taking conjugated oestrogens who do not smoke should avoid starting, and those who do smoke should talk with their doctor about giving up.

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References
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