ESTROGENS (COMBINED)

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.