Short- and long-term impact of gonadotropin-releasing hormone analogue treatment on bone loss and fracture

Sauerbrun‐Cutler, May‐Tal; Alvero, Ruben

doi:10.1016/j.fertnstert.2019.09.037

Cited by 33 publications

(37 citation statements)

References 33 publications

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“…56 To mitigate the hypoestrogenic effects of GnRH agonists, including reductions in BMD, they may be administered in conjunction with add-back therapy to restore estrogen to a level at which bone loss is prevented but endometrial tissue is not stimulated. 11 Data from meta-analyses 57,58 and recent studies 59,60 confirm that add-back therapy mitigates bone loss associated with GnRH agonist treatment.…”

Section: Gnrh Agonistsmentioning

confidence: 91%

“…GnRH agonists are used in the treatment of multiple conditions affecting premenopausal women, including endometriosis, uterine fibroids, and adenomyosis, as well as for fertility preservation. 11 After an initial flare of pituitary gonadotrophs, GnRH agonist administration profoundly reduces luteinizing hormone and follicle-stimulating hormone levels, thereby suppressing estrogen and progesterone production. This mechanism of action induces maximum ovarian suppression, with associated side effects that include decreases in BMD.…”

Section: Gnrh Agonistsmentioning

confidence: 99%

“…This mechanism of action induces maximum ovarian suppression, with associated side effects that include decreases in BMD. 11 Sauerbrun-Cutler and Alvero 11 reviewed the effects of GnRH agonists on bone loss and fracture in 2019. They cite bone loss with GnRH agonists of 2%-6% in total hip, lumbar spine, and proximal femur, with partial to full recovery observed 1 year after treatment cessation.…”

Section: Gnrh Agonistsmentioning

confidence: 99%

“…The influence of these drug-related reductions in BMD on risk of fracture later in life has not been well established. 10,11 Given the increased risk with age at the population level, the bulk of evidence regarding fracture likelihood relates to older postmenopausal women. 12 However, events during the premenopausal years have the potential to influence BMD trajectory throughout the life span 13 and could affect risk of fracture later in life.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life

Watts

Binkley

Owens

et al. 2021

Journal of Women's Health

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Bone mineral density (BMD) changes during the life span, increasing rapidly during adolescence, plateauing in the third decade of life, and subsequently entering a phase of age-related decline. In women, menopause leads to accelerated bone loss and an increase in fracture risk. Between peak bone mass attainment and menopause, BMD is generally stable and the risk of fracture is typically low. This time period is marked by life events such as pregnancy and lactation, which transiently decrease BMD, yet their long-term effects on fracture risk are less certain. BMD may also be altered by exposure to medications that affect bone metabolism (e.g., contraceptives, glucocorticoids, antidiabetic medications, antiepileptic drugs). Although oral contraceptives are often believed to be neutral with regard to bone health, depot medroxyprogesterone acetate (DMPA) and gonadotropinreleasing hormone (GnRH) agonists have been associated with decreases in BMD. Development of newer medical therapies, principally GnRH antagonists (e.g., ASP1707, elagolix, linzagolix, relugolix), for treatment of endometriosis-associated pelvic pain and heavy menstrual bleeding due to uterine fibroids has renewed interest in the short-and long-term impacts of changes in BMD experienced by premenopausal women. It is important to understand how these drugs influence BMD and put the findings into context with regard to measurement variability and naturally occurring factors that influence bone health. This review summarizes what is known about the effects on bone health pregnancy, lactation, and use of DMPA, GnRH agonists, and GnRH antagonists in premenopausal women and potential consequences later in life. ClinicalTrials.gov identifier: NCT03213457.

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Section: Gnrh Agonistsmentioning

confidence: 91%

Section: Gnrh Agonistsmentioning

confidence: 99%

Section: Gnrh Agonistsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life

Watts

Binkley

Owens

et al. 2021

Journal of Women's Health

View full text Add to dashboard Cite

show abstract

“…Previous studies have revealed that women with endometriosis did not exhibit a decrease in BMD compared to women of the same age without endometriosis [18,19], and that long-term fracture risks did not increase in women with endometriosis [20]. Meanwhile, regarding the decrease in BMD as a side effect of hormone therapy, the impact of add-back therapy using gonadotropin-release hormone analogues and oestrogen preparations for bone protection [21], as well as the decrease in BMD due to long-term administration of Dienogest, a progestin preparation [22] have been investigated. Another report suggested that BMD was higher after ovariectomy for deep endometriosis than after ovariectomy for other indications [23].…”

Section: Introductionmentioning

confidence: 99%

Relationship Between Bone Mineral Density and Ovarian Function in Perimenopausal Women With Endometriosis: A Prospective Study

Uehara

Wada‐Hiraike

Hirano

et al. 2021

Preprint

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Background In women with endometriosis, the association between ovarian function, hormones, and bone mineral density (BMD) is unclear. Therefore, this study aimed to elucidate the correlation between changes in bone mineral density (BMD) in perimenopausal women with endometriosis and clinical data, such as ovarian reserves. Methods In this prospective study, we evaluated 207 female patients who visited the Department of Obstetrics and Gynecology at the University of Tokyo Hospital between December 2015 and December 2020. We included patients aged ≥ 40 years with a history of endometriosis or who presented with endometriosis lesions. Patients with a history of smoking, steroid administration, autoimmune diseases, dyslipidaemia, and heart disease were excluded. During the study period, patients who underwent two tests, an initial and a follow-up test (n = 142, average age: 45.02 years, average BMD: 1.16 g/cm2), were evaluated at regular intervals based on the annual rate of change in BMD. Results There was a negative correlation between the follicle-stimulating hormone (FSH) and BMD, and a positive correlation between the anti-Müllerian hormone (AMH) and BMD. The annual rate of change in BMD correlated only with thyroid-stimulating hormone (TSH) levels. A large decline in BMD was associated with high TSH levels and higher average age at menopause. Patients with higher TSH exhibited a higher rate of decrease in BMD than those without. Conclusions High FSH or low AMH levels are associated with decreased BMD. Decreased ovarian reserve is associated with decreased BMD in perimenopausal women with endometriosis. High TSH levels increase the risk of BMD loss. This finding may help manage osteoporosis and BMD loss in perimenopausal women with endometriosis by predicting BMD loss from ovarian reserve and TSH levels.

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Three cases highlighting possible discrepancies in the interpretation of transgender DXA scores

De La Torre,

Godar,

Shakir

et al. 2024

Clinical Case Reports

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Key Clinical MessageFor diagnosis of osteoporosis, a T‐score of ≤−2.5 is recommended for all transgender and gender‐diverse patients aged 50 years or older, regardless of hormonal status. This case series presents 3 transgender individuals younger than 50 years undergoing gender‐affirming hormone therapy (GAHT) who had DXA scores suggestive of osteoporosis. We highlight possible discrepancies in DXA scan interpretations, especially in forearm bone mineral density measurements. We present the baseline (prior to beginning GAHT), 6‐month, and 1‐year follow‐up DXA data along with pertinent labs to include 25‐OH vitamin D, calcium, and alkaline phosphatase, for 2 transgender males (assigned female at birth) and 1 transgender female (assigned male at birth) undergoing GAHT who had low Z‐scores and T‐scores suggestive of osteoporosis. Multiple studies have analyzed the BMD data of individuals taking GAHT over time, which identify possible causes for low baseline Z‐scores for transgender females, but less so for transgender males. Other than positional statements, guidelines remain unclear regarding diagnostic approaches to osteoporosis and low Z‐scores in transgender individuals who are premenopausal or under 50 years of age. This case series addresses discrepancies in interpretation that may be encountered by clinicians with baseline and follow‐up DXAs, especially involving the forearm, during the course of GAHT. This highlights the importance of establishing clearer guidelines for the diagnosis and treatment of osteoporosis and low BMD for chronological age in the transgender population.

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Short- and long-term impact of gonadotropin-releasing hormone analogue treatment on bone loss and fracture

Cited by 33 publications

References 33 publications

Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life

Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life

Relationship Between Bone Mineral Density and Ovarian Function in Perimenopausal Women With Endometriosis: A Prospective Study

Three cases highlighting possible discrepancies in the interpretation of transgender DXA scores

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