Depot Medroxyprogesterone Acetate, Oral Contraceptive, Intrauterine Device Use, and Fracture Risk

Raine‐Bennett, Tina; Chandra, Malini; Armstrong, Mary Anne; Alexeeff, Stacey; Lo, Joan C.

doi:10.1097/aog.0000000000003414

Cited by 12 publications

(7 citation statements)

References 18 publications

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“… 40 , 41 Several studies indicated that oral progestin and progestin-eluting IUDs had an unapparent hypoestrogenic effect, 42 except that DMPA users may encounter more menopausal symptoms. 40 , 43 , 44 In this study, we detected signals of heart rate irregular, bone disorder, osteopenia, and autonomic nervous system imbalance in depot progestin users. Signals of feeling hot, abnormal weight gain, and loss of libido were detected in progestin-eluting IUD users as well.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Adverse Events and Medical Errors in Long-Term Hormone Treatments for Endometriosis: A Study Based on the US Food and Drug Administration Event Reporting System

Zhang¹,

Zhu²,

Sun³

2022

IJWH

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Purpose To investigate adverse events and medical errors, as well as their possible risk factors, of combined oral contraceptives and progestins used in patients with endometriosis. Patients and Methods Reports between January 1, 2014 and September 30, 2021 about patients with endometriosis in US Food and Drug Administration Adverse Event Reporting System were analyzed. Disproportional analysis was performed with the Gamma-Poisson Shrinker model to detect overreported drug-event pairs. Logistic regression analysis was utilized to explore potential risk factors. Results There were 823 reports on long-term hormone treatments and 6247 reports on other drugs after removing duplicates, most of which were reported by consumers and were from the United States. Procedural complications and product issues were common among long-term hormone treatment users, while some other new adverse events emerged in subgroup analysis of different dosage forms of progestin. Polytherapy was negatively associated with off label use (adjusted OR = 0.47, 95% CI 0.22–0.94) and product use in unapproved indication (adjusted OR = 0.36, 95% CI 0.15–0.76) for combined oral contraceptive users. Combined oral contraceptive users aged greater than or equal to 30 were less likely to have product use issue (adjusted OR = 0.33, 95% CI 0.12–0.82) but were at higher risk of pulmonary embolism (adjusted OR = 4.04, 95% CI 1.35–17.43). Conclusion Long-term hormone treatment products in this study are generally safe for endometriosis, while newly detected signals need to be validated by further exploration. Patients’ tolerance and fertility desire should be considered when preparing treatment plans.

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Section: Discussionmentioning

confidence: 99%

Analysis of Adverse Events and Medical Errors in Long-Term Hormone Treatments for Endometriosis: A Study Based on the US Food and Drug Administration Event Reporting System

Zhang¹,

Zhu²,

Sun³

2022

IJWH

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“…Among studies that focused on osteoporosis-related fractures, there was a signal for a small increase in fracture risk for DMPA users versus nonusers (Table 2). [53][54][55] Notably, data were derived predominantly from younger populations, creating a skew toward premenopausal women. It remains to be determined what effect a history of DMPA use has on fracture risk in postmenopausal women.…”

Section: Effects Of Dmpa Gnrh Agonists and Gnrh Antagonists On Bone Healthmentioning

confidence: 99%

“…Studies of DMPA users, however, suggest that fracture risk is slightly elevated among premenopausal women. 53,55 For GnRH agonists and GnRH antagonists, clinical trials have not shown an increase in fracture risk, but the sample size, duration of follow-up, and low baseline risk of the study populations limit the ability to detect rare fracture events. In postmenopausal women, data indicate no increased fracture risk associated with prior pregnancy or lactation and are insufficient for DMPA and GnRH agonists or antagonists.…”

Section: Clinical Perspectivementioning

confidence: 99%

“…15,74,75 As a population, the risk of fracture is low in premenopausal women, even in subgroups with risk factors such as medication use. 53,55 Moreover, percent changes from baseline in BMD observed with DMPA and GnRH antagonist use are modest, particularly during short-term treatment, and may not be detectable at the individual level due to the innate variability of densitometry (Table 4). Post-treatment group level data also indicate at least partial BMD recovery after treatment cessation.…”

Section: Clinical Perspectivementioning

confidence: 99%

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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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“…A subsequent retrospective study from a large health care group in the United States compared non-traumatic fracture rates in 308,876 women (ages 12-45) who began use of COC, progestin-only pills, DMPA or IUDs (copper or levonogesterol) between 2005 and 2015 (54). Women with more than 2 years of cumulative use of COCs or progestin-only contraceptive pills had lower fracture risk compared to those who had not used OCPs [adjusted HR 0.85 (95% CI 0.76-0.960)] or used other methods [0.88 (95% CI 0.80-0.97)].…”

Section: Hormonal Contraceptives and Fracturesmentioning

confidence: 99%

Hormonal Contraception and Bone Health in Adolescents

Bachrach

2020

Front. Endocrinol.

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Hormonal contraception is prescribed commonly to adolescents for myriad indications from pregnancy prevention to treatment for acne, hirsutism or dysmenorrhea. Although use of these hormones generally has no effect or benefits bone health in mature premenopausal women, the same may not be true for adolescents. The teen years are a critical period for acquiring peak bone strength. Sex hormones, growth hormone, and insulin-like growth factors (IGFs) interact to modulate the changes in bone size, geometry, mineral content, and microarchitecture that determine skeletal strength. Combined oral contraceptives (COCs) and intramuscular depo medroxyprogesterone (DMPA) can compromise the expected gains in adolescence by altering estrogen and IGF concentrations. Use of these medications has been associated with slower accrual of bone mineral density (BMD) and increased fracture risk in some studies. Far less is known about the skeletal effects of the newer long acting reversible contraceptives (LARCs). This review takes a critical look at the gaps in current knowledge of the skeletal effects of COCs, DMPA, and LARCs and underscores the need for additional research.

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Depot Medroxyprogesterone Acetate, Oral Contraceptive, Intrauterine Device Use, and Fracture Risk

Abstract: Personal or nonessential information may be redacted at the editor's discretion.

Cited by 12 publications

References 18 publications

Analysis of Adverse Events and Medical Errors in Long-Term Hormone Treatments for Endometriosis: A Study Based on the US Food and Drug Administration Event Reporting System

Analysis of Adverse Events and Medical Errors in Long-Term Hormone Treatments for Endometriosis: A Study Based on the US Food and Drug Administration Event Reporting System

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

Hormonal Contraception and Bone Health in Adolescents

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