Early Oophorectomy Linked to Osteoporosis, Arthritis

SAN ANTONIO – Bilateral oophorectomy in women younger than age 45 is associated with a subsequent doubled prevalence of osteoporosis and a similarly elevated rate of arthritis, compared with women with intact ovaries.

These findings from a new analysis of the Third National Health and Nutrition Examination Survey (NHANES III) had a further twist: The likelihood of having low bone mineral density and/or arthritis was even greater in the subgroup of women not on hormone replacement therapy following their surgically-induced abrupt menopause, Anne Marie McCarthy said at the San Antonio Breast Cancer Symposium.

"The implication of our findings is that women who’ve had their ovaries removed at a young age can now be informed about their risk for bone loss over the long term. However, additional studies are needed to determine the frequency of monitoring for osteoporosis and the appropriateness of various preventive strategies in women who’ve had their ovaries removed," according to Ms. McCarthy, a doctoral candidate in epidemiology at Johns Hopkins University, Baltimore.

The bone mineral density analysis included 3,660 women who underwent femoral neck bone density measurement by dual energy x-ray as part of their participation in NHANES III, which was conducted in a U.S. nationally representative sample in 1988-1994.

The age-standardized mean femoral neck bone density was significantly lower in women with oophorectomy before age 45 than in those with intact ovaries: 0.711 compared with 0.743 g/m² (P = .017). Moreover, in a multivariate logistic regression analysis, women with early oophorectomy had an adjusted 1.78-fold increased likelihood of having osteoporosis, compared with women with intact ovaries. Upon exclusion of hormone replacement therapy users, the odds climbed even higher so that oophorectomy before age 45 was associated with a 2.92-fold increased likelihood of osteoporosis, she reported.

The Johns Hopkins investigators are now in the midst of a study in which they’re measuring bone mineral density before and after prophylactic oophorectomy in women who carry high-risk BRCA mutations.

The arthritis analysis included 4,039 women. Those who had undergone oophorectomy were significantly more likely to report having been informed by a physician that they have arthritis, by a margin of 45.4% to 32.1% (P less than .001). Among the subset of women with oophorectomy before age 45, the prevalence of arthritis was even higher at 47.7%. In a multivariate analysis, women with oophorectomy when they were younger than 45 had a 1.78-fold increased odds of arthritis compared with those with intact ovaries. If they didn’t use hormone replacement therapy, however, those odds rose to 1.99-fold.

Because the investigators didn’t study the NHANES III participants’ actual medical records, they were unable to say what specific forms of arthritis were more prevalent in the early oophorectomy group. Also, since to Ms. McCarthy’s knowledge this is the first-ever study linking oophorectomy to arthritis, this association needs confirmation by others. There are animal data supporting such a link, she noted.

"One possible mechanism is that we think estrogen is important for the health of cartilage, so losing estrogen can lead to inflammation and damage of cartilage, perhaps," Ms. McCarthy speculated.

Prophylactic bilateral oophorectomy is a widely accepted procedure to reduce the risks of breast and ovarian cancer in BRCA mutation carriers. But this indication actually accounts for only a small fraction of oophorectomies performed in this country. About 600,000 women per year undergo hysterectomy for indications including fibroids, abnormal bleeding, endometriosis, and uterine prolapse, according to the Centers for Disease Control and Prevention, and about half of them have both ovaries removed at that time to prevent ovarian cancer.

NHANES III was conducted by the CDC. Ms. McCarthy said she had no relevant financial disclosures.

SAN ANTONIO – Bilateral oophorectomy in women younger than age 45 is associated with a subsequent doubled prevalence of osteoporosis and a similarly elevated rate of arthritis, compared with women with intact ovaries.

These findings from a new analysis of the Third National Health and Nutrition Examination Survey (NHANES III) had a further twist: The likelihood of having low bone mineral density and/or arthritis was even greater in the subgroup of women not on hormone replacement therapy following their surgically-induced abrupt menopause, Anne Marie McCarthy said at the San Antonio Breast Cancer Symposium.

"The implication of our findings is that women who’ve had their ovaries removed at a young age can now be informed about their risk for bone loss over the long term. However, additional studies are needed to determine the frequency of monitoring for osteoporosis and the appropriateness of various preventive strategies in women who’ve had their ovaries removed," according to Ms. McCarthy, a doctoral candidate in epidemiology at Johns Hopkins University, Baltimore.

The bone mineral density analysis included 3,660 women who underwent femoral neck bone density measurement by dual energy x-ray as part of their participation in NHANES III, which was conducted in a U.S. nationally representative sample in 1988-1994.

The age-standardized mean femoral neck bone density was significantly lower in women with oophorectomy before age 45 than in those with intact ovaries: 0.711 compared with 0.743 g/m² (P = .017). Moreover, in a multivariate logistic regression analysis, women with early oophorectomy had an adjusted 1.78-fold increased likelihood of having osteoporosis, compared with women with intact ovaries. Upon exclusion of hormone replacement therapy users, the odds climbed even higher so that oophorectomy before age 45 was associated with a 2.92-fold increased likelihood of osteoporosis, she reported.

The Johns Hopkins investigators are now in the midst of a study in which they’re measuring bone mineral density before and after prophylactic oophorectomy in women who carry high-risk BRCA mutations.

The arthritis analysis included 4,039 women. Those who had undergone oophorectomy were significantly more likely to report having been informed by a physician that they have arthritis, by a margin of 45.4% to 32.1% (P less than .001). Among the subset of women with oophorectomy before age 45, the prevalence of arthritis was even higher at 47.7%. In a multivariate analysis, women with oophorectomy when they were younger than 45 had a 1.78-fold increased odds of arthritis compared with those with intact ovaries. If they didn’t use hormone replacement therapy, however, those odds rose to 1.99-fold.

Because the investigators didn’t study the NHANES III participants’ actual medical records, they were unable to say what specific forms of arthritis were more prevalent in the early oophorectomy group. Also, since to Ms. McCarthy’s knowledge this is the first-ever study linking oophorectomy to arthritis, this association needs confirmation by others. There are animal data supporting such a link, she noted.

"One possible mechanism is that we think estrogen is important for the health of cartilage, so losing estrogen can lead to inflammation and damage of cartilage, perhaps," Ms. McCarthy speculated.

Prophylactic bilateral oophorectomy is a widely accepted procedure to reduce the risks of breast and ovarian cancer in BRCA mutation carriers. But this indication actually accounts for only a small fraction of oophorectomies performed in this country. About 600,000 women per year undergo hysterectomy for indications including fibroids, abnormal bleeding, endometriosis, and uterine prolapse, according to the Centers for Disease Control and Prevention, and about half of them have both ovaries removed at that time to prevent ovarian cancer.

NHANES III was conducted by the CDC. Ms. McCarthy said she had no relevant financial disclosures.

SAN ANTONIO – Bilateral oophorectomy in women younger than age 45 is associated with a subsequent doubled prevalence of osteoporosis and a similarly elevated rate of arthritis, compared with women with intact ovaries.

These findings from a new analysis of the Third National Health and Nutrition Examination Survey (NHANES III) had a further twist: The likelihood of having low bone mineral density and/or arthritis was even greater in the subgroup of women not on hormone replacement therapy following their surgically-induced abrupt menopause, Anne Marie McCarthy said at the San Antonio Breast Cancer Symposium.

"The implication of our findings is that women who’ve had their ovaries removed at a young age can now be informed about their risk for bone loss over the long term. However, additional studies are needed to determine the frequency of monitoring for osteoporosis and the appropriateness of various preventive strategies in women who’ve had their ovaries removed," according to Ms. McCarthy, a doctoral candidate in epidemiology at Johns Hopkins University, Baltimore.

The bone mineral density analysis included 3,660 women who underwent femoral neck bone density measurement by dual energy x-ray as part of their participation in NHANES III, which was conducted in a U.S. nationally representative sample in 1988-1994.

The age-standardized mean femoral neck bone density was significantly lower in women with oophorectomy before age 45 than in those with intact ovaries: 0.711 compared with 0.743 g/m² (P = .017). Moreover, in a multivariate logistic regression analysis, women with early oophorectomy had an adjusted 1.78-fold increased likelihood of having osteoporosis, compared with women with intact ovaries. Upon exclusion of hormone replacement therapy users, the odds climbed even higher so that oophorectomy before age 45 was associated with a 2.92-fold increased likelihood of osteoporosis, she reported.

The Johns Hopkins investigators are now in the midst of a study in which they’re measuring bone mineral density before and after prophylactic oophorectomy in women who carry high-risk BRCA mutations.

The arthritis analysis included 4,039 women. Those who had undergone oophorectomy were significantly more likely to report having been informed by a physician that they have arthritis, by a margin of 45.4% to 32.1% (P less than .001). Among the subset of women with oophorectomy before age 45, the prevalence of arthritis was even higher at 47.7%. In a multivariate analysis, women with oophorectomy when they were younger than 45 had a 1.78-fold increased odds of arthritis compared with those with intact ovaries. If they didn’t use hormone replacement therapy, however, those odds rose to 1.99-fold.

Because the investigators didn’t study the NHANES III participants’ actual medical records, they were unable to say what specific forms of arthritis were more prevalent in the early oophorectomy group. Also, since to Ms. McCarthy’s knowledge this is the first-ever study linking oophorectomy to arthritis, this association needs confirmation by others. There are animal data supporting such a link, she noted.

"One possible mechanism is that we think estrogen is important for the health of cartilage, so losing estrogen can lead to inflammation and damage of cartilage, perhaps," Ms. McCarthy speculated.

Prophylactic bilateral oophorectomy is a widely accepted procedure to reduce the risks of breast and ovarian cancer in BRCA mutation carriers. But this indication actually accounts for only a small fraction of oophorectomies performed in this country. About 600,000 women per year undergo hysterectomy for indications including fibroids, abnormal bleeding, endometriosis, and uterine prolapse, according to the Centers for Disease Control and Prevention, and about half of them have both ovaries removed at that time to prevent ovarian cancer.

NHANES III was conducted by the CDC. Ms. McCarthy said she had no relevant financial disclosures.