Long-term Use Of Depot Medroxyprogesterone Acetate Research Articles

Depot Medroxyprogesterone Acetate and Bone Mineral Density

Background: Previous studies have suggested that depot medroxyprogesterone acetate (DMPA) may result in a reduction in bone mineral density (BMD). This study further explores this relationship. This study was undertaken to assess the association between long-term DMPA use and areal BMD (aBMD) in a uniform manner in a single private specialist practice over two decades. Methods: Of 1,046 consecutive patients using DMPA in a single Melbourne specialist’s practice between 1981 and 2013, from 1992 102 were referred for dual-energy X-ray absorptiometry (DXA) scans. Each was matched for age and body mass index with two participants from a reference group of 1,416 healthy female volunteers who underwent DXA scans at the Royal Melbourne Hospital. Results: A total of 306 participants were included in this study, 102 cases and 204 referents. DMPA users had lower aBMD at first testing (median duration of DMPA use 4.3 years (IQR 2.6 - 6.7 years) compared with the reference group, and lower aBMD persisted in users 2 - 5 years post cessation of DMPA. These differences from the reference group were statistically and potentially clinically significant. There was no evidence of accelerated bone loss at any site in the DMPA users during longitudinal observations on treatment, but the study had limited power to detect such an effect. Conclusions: DMPA use was associated with aBMD deficits during and after treatment. The findings demonstrate that long-term, controlled, prospective studies with adequate sample size are required to evaluate the potential clinical impact of DMPA use on bone health outcomes. J Clin Gynecol Obstet. 2018;7(3-4):63-68 doi: https://doi.org/10.14740/jcgo519

Bone mineral density in midlife long-term users of hormonal contraception in South Africa: relationship with obesity and menopausal status

BackgroundIn South Africa, hormonal contraception is widely used in women over the age of 40 years. One of these methods and the most commonly used is depot-medroxyprogesterone acetate (DMPA) which has been found to have a negative effect on bone mass. Limited information is available on the effect of norethisterone enanthate (NET-EN) on bone mass, and combined oral contraceptives (COCs) have not been found to be associated with loss of bone mass. The aim of this study was to investigate bone mineral density (BMD) in pre and perimenopausal women (40–49 years) in relation to use of DMPA, NET-EN and COCs for at least 12 months preceding recruitment into the study and review associations with body mass index (BMI) and menopausal status.MethodsOne hundred and twenty seven users of DMPA, 102 NET-EN users and 106 COC users were compared to 161 nonuser controls. Menopausal status was assessed, BMI and forearm BMD was measured at the distal radius using dual X-ray absorptiometry. Comparison analysis was conducted at baseline and 2.5 years.ResultsThere was no significant difference in BMD between the four contraceptive user groups (p = 0.26) with and without adjustment for age at baseline or at 2.5 years (p = 0.52). The BMD was found to be significantly associated with BMI (p = < 0.0001) with an increase of one unit of BMI translating to an increase of 0.0044 g/cm2 in radius BMD. Follicle stimulating hormone (FSH) level ≥ 25.8 mIU/mL was associated with a decrease of 0.017 g/cm2 in radius BMD relative to women with FSH < 25.8 mIU/mL. Significant interaction between FSH and BMI in their effect on BMD was observed (p = .006).ConclusionThis study found no evidence that long-term use of DMPA, NET-EN and COCs affects forearm BMD in this population at baseline or after 2.5 years of follow-up. This study also reports the complex relationship and significant interaction between FSH and BMI in their effect on BMD. BMD research in older women needs to ensure that women are assessed for menopausal status and BMI.

Vaginal Atrophy following Long-Term Depot Medroxyprogesterone Acetate Use: A Case Report

Depot medroxyprogesterone acetate (DMPA) is a commonly used form of contraception, with noncontraceptive benefits for the user. The mode of action is through the suppression of ovulation. It leads to hypoestrogenism which causes dryness of the vagina and dyspareunia. We present in this paper a patient that was very symptomatic with regard to vaginal atrophic changes determined by vaginal cytology. This side effect may become increasingly more common as we see more long-term use of DMPA.

A cross-sectional study of the forearm bone mineral density in long-term current users of the injectable contraceptive depot medroxyprogesterone acetate

Background One of the well-established effects of the use of depot medroxyprogesterone acetate (DMPA) contraception is on bone mineral density (BMD). However, little evidence assesses the skeletal impact of long-term DMPA use. The objective of this study was to assess BMD on a cohort of women who used DMPA uninterruptedly between 1 and 15 years. Study Design A cross-sectional study with 232 users of DMPA matched to a group of 232 copper intrauterine device (IUD) users by age (±1) (range 20–53 and 20–51 years for DMPA and IUD group, respectively), body mass index (BMI; kg/m 2) (±1) (range 17.4–44.5 and 18.5–40.2 for DMPA and IUD group, respectively) and years of use (1–15 years) was performed. The women underwent forearm BMD evaluation using dual-energy X-ray absorptiometry. The women were divided into five groups (1–5) according to the length of DMPA use: 1–3, 4–6, 7–9, 10–12 and 13–15 years of use. Results The mean (±SEM) age was 38.3±0.5 and 38.1±0.57 years and the mean (±SEM) BMI (kg/m 2) was 26.4±0.3 and 26.3±0.3 for the entire group of women in the DMPA and IUD group, respectively. Women who used DMPA or IUD for a short time were younger and had lower BMI (kg/m 2) than the women who used either contraceptive method long term. White women were significantly more frequent among IUD users (p<.040) than DMPA users. In addition, parity (p<.053) and physical activity (p<.012) were significantly greater among IUD users, whereas the prevalence of washing clothes by hand (p<.025) was significantly greater among DMPA users. There was no significant difference in BMD measurements between the current users of DMPA and those who had used the IUD either at the distal or ultra-distal sections of the forearm. However, women who had used DMPA for 13–15 years showed significantly lower BMD at the distal and ultra-distal radius when compared to IUD users (p<.041 and .042, respectively). Otherwise, all other differences in BMD values between DMPA and IUD users were nonsignificant at the distal and ultra-distal radius. For both DMPA and IUD users, we noted a direct correlation between higher BMD and BMI (kg/m 2) and an inverse correlation between BMD and age for distal and ultra-distal radius. Conclusions Our study did not detect a deleterious effect on measurements of forearm BMD among long-term DMPA users with less than 13 years of use; however, a significantly lower BMD was observed at 13–15 years of use in DMPA users when compared to IUD users. Bone mineral density was inversely correlated to older age and directly correlated to BMI (kg/m 2).

Effects of the long-term use of depot medroxyprogesterone acetate as hormonal contraceptive on bone mineral density and biochemical markers of bone remodeling

Purpose and Method Our objective is to evaluate the effects of the long-term use of depot medroxyprogesterone acetate (DMPA) as a method of contraception on bone mineral density (BMD) and bone remodeling. Forty women (21–44 years old) who used DMPA for contraception for <1, 1–2 and >5 years, in addition to 20 age-matched healthy women (nonusers), participated in this study. Lumbar spine BMD (LS-BMD) was measured by dual-energy X-ray absorptionmetry. Serum osteocalcin (OC), a bone formation marker, was measured by enzyme amplification sorbent immunoassay. Urinary deoxypyridinoline (DPD), a bone resorption marker, was determined by enzyme immunoassay. Results Serum OC and urinary DPD levels in women who used DMPA for <1, 1–2 and >5 years were significantly increased compared to the corresponding levels in nonusers. The increase of both biomarkers was more pronounced with longer duration of use. LS-BMD was significantly decreased in women on long-term DMPA use compared to LS-BMD in nonusers. The mean percentage decrease of LS-BMD in women who used DMPA for 1–2 and >5 years was 9% and 11.8%, respectively. LS-BMD was negatively correlated with serum OC and urinary DPD in women who used DMPA. On the other hand, LS-BMD and bone turnover were not significantly different between women who used DMPA for <1 year and nonusers. Conclusion Long-term use of DMPA (>2 years) had a significant adverse effect on BMD and induced increased bone turnover, as evidenced by a significant increase in biochemical indices of bone formation and resorption. The measurement of LS-BMD and of biomarkers of bone turnover may be recommended in women aged above 40 years and who used DMPA for a long duration (2–5 years).

Bone mineral density in women aged 40–49 years using depot-medroxyprogesterone acetate, norethisterone enanthate or combined oral contraceptives for contraception

Most studies show that depot-medroxyprogesterone acetate (DMPA) has a negative effect on bone mass. There are conflicting reports with respect to recovery of bone mass with long-term use of DMPA. No information is available on the effect of norethisterone enanthate (NET-EN) on bone mass, and combined oral contraceptives (COCs) have not been found to be associated with loss of bone mass. The aim of this study was to investigate bone mineral density (BMD) in older women (40–49 years) in relation to use of DMPA, NET-EN and COCs for at least 12 months preceding recruitment into the study. One-hundred twenty-seven users of DMPA, 102 NET-EN users and 106 COC users were compared to 161 nonuser controls. Bone mineral density was measured at the distal radius and midshaft of the ulna using dual X-ray absorptiometry. There was no significant difference in BMD between the four contraceptive user groups (p=.26) with and without adjustment for age. Although a small decrease in BMD was noted in the age range of 40–49 years, this was not statistically significant (p=.7). The BMD was found to be significantly associated with body mass index (BMI) (p≤.0001) at both measurement sites, with an increase of one unit of BMI translating to an increase of 0.0044 g/cm 2 in radius BMD. Follicle-stimulating hormone (FSH) level ≥25.8 mIU/mL was associated with a decrease of 0.017 g/cm 2 in radius BMD relative to women with FSH <25.8 mIU/mL. Significant interaction between FSH and BMI in their effect on BMD was observed (p=.006). This study found no evidence that long-term use of DMPA, NET-EN and COCs affects BMD in this population.

Bone mineral density in adolescent women using depot medroxyprogesterone acetate.

To present current data on bone mineral density (BMD) in adolescent women using the long-acting contraceptive depot medroxyprogesterone acetate (DMPA) and also to discuss the importance of developing maximal bone mass during adolescence to offset bone demineralization later in life. Research-based articles in the medical literature, review articles, and recommendations from the American Academy of Pediatrics and the National Osteoporosis Foundation. Osteoporosis is a preventable disease that affects millions of Americans, particularly older women. Factors influencing the attainment and maintenance of peak bone mass during childhood and adolescence affect the future risk of fractures. Although longitudinal studies conducted on adolescent women using DMPA are very limited, findings suggest that adolescents are losing bone density during a time of expected bone accretion. Clinicians must consider all the risks and benefits when prescribing contraceptives to adolescents. By themselves, the findings related to BMD and DMPA use by adolescents are not sufficient to limit the use of DMPA as a contraceptive method. However, clinicians must take into account the addition of other modifying factors associated with BMD that may contribute to overall bone loss in adolescent females. More prospective data on the long-term use of DMPA by adolescents are needed to determine DMPA's effect on bone loss and to determine if bone loss is transient in adolescents.

Further evaluation on long-term depot-medroxyprogesterone acetate use and bone mineral density: a longitudinal cohort study

Cross-sectional studies on the effects of depot-medroxyprogesterone acetate (DMPA) on bone mineral density (BMD) have been controversial. The present longitudinal cohort study on 59 Chinese women over a period of 3 years has shown that their annual rate of bone loss at 3 sites (0.44% in lumbar spine, 0.40% in neck of femur, 1.05% in Ward’s triangle) was substantially less than the projected values (1.1% in lumbar spine, 2.3% in neck of femur, 3.5% in Ward’s triangle) in a cross-sectional study that had demonstrated a significant reduction in BMD in DMPA users than the non-user population. The trochanter BMD measurement did not show the projected annual bone loss of 2.4%. The rate of bone loss is probably non-linear, with a rapid loss in the first 5 years and a leveling off afterwards. The duration of DMPA use was not significantly correlated with the rate of bone loss. Multiple linear regression analysis demonstrated that age and body mass index were significant variables in modeling the rate of bone loss in the lumbar spine and neck of femur, but not in the trochanter and Ward’s triangle areas. The Z scores also suggested a retardation in bone loss with time and potentially due to the effect of progesterone in decreasing bone turnover that is similar to the situation in postmenopausal women. The present data provide another aspect of reassurance to the long-term use of DMPA.

Long-term depot-medroxyprogesterone acetate and bone mineral density

The association between long-term use of depot-medroxyprogesterone acetate (DMPA) and bone mineral density (BMD) has been controversial, as seen in three case-control studies in New Zealand, Thailand, and the United Kingdom. In the present case-controlled study of BMD, a group of 67 Chinese women who had used DMPA from 5–15 years was compared with 218 women of the same age range who had not used any steroidal hormones. DMPA users were found to have a significantly lower BMD at lumbar vertebra (L2–4) (0.93 g/cm 2), neck of femur (0.69 g/cm 2), trochanter (0.59 g/cm 2), and Ward’s triangle (0.58 g/cm 2), as compared with the control group, whose corresponding BMD values were 1.03 g/cm 2, 0.83 g/cm 2, 0.71 g/cm 2, and 0.78 g/cm 2, respectively (p <0.001). The average percentage of bone loss per year was estimated to be 1.1% in L2–4, 2.3% in neck of femur, 2.4% in trochanter, and 3.5% in Ward’s triangle. The percentage of bone loss in L2–4 was found to be more pronounced with age. This study provided information that the use of DMPA in a Chinese group for >5 years is associated with bone loss, and a prospective study is needed to confirm these data, which are different from two case-control studies.

Comparative study of weight change between long-term DMPA and IUD acceptors

The study of weight gain in long-term depot-medroxyprogesterone acetate (DMPA) acceptors is reported. The objectives were to study and compare weight gain in long-term DMPA acceptors with intrauterine device (IUD) acceptors. Fifty healthy women who had been using DMPA for 120 months were compared to 50 IUD acceptors who had been using IUD for 120 months as control. Age, parity, income, and weight at the initiation of contraception were matched. The mean ± SD body weight at 120 months in DMPA and IUD groups were 60.9 ± 7.5 kg and 62.1 ± 9.3 kg, respectively. The mean change in body weight in DMPA and IUD groups were 10.9 ± 1.2 and 11.2 ± 1.5 kg. No difference in mean body weight between DMPA and IUD acceptors was demonstrated. It is suggested that weight gain in long-term DMPA use should not be different from nonhormonal contraception. DMPA should not have an unfavorable effect on weight in long-term users.

Depression in users of depo-medroxyprogesterone acetate

Prevalence of depression is high among poor, young, Hispanic inner city women. Depot-medroxyprogesterone acetate (DMPA) is a popular contraceptive choice in this group. DMPA labelling suggests that depression may worsen with use: In order to identify any association of DMPA use with worsening depression, we surveyed an English-speaking subset of DMPA users in a Title-X funded family planning clinic. Eighty women completed the CES-D scale on two occasions: once about four weeks after a DMPA injection when the subject would have been exposed to the highest blood levels, and once immediately prior to an injection when recent blood levels of the drug would be somewhat lower (or absent preceding the first injection). The median CES-D score was 14. The scores were not related to timing of the test (pre- or post-injection). The depression scores were somewhat higher among those women receiving their first DMPA injection during the study period (i.e., unexposed women) and among those women who had received four or more injections. Scores were unrelated to age or parity, but were somewhat higher in women who reported fewer years of education or a recent adverse pregnancy outcome. These data provide little evidence of increasing depression with long-term use of DMPA and no evidence of a short-term effect of dose (within the contraceptive range) on mood. Women at risk of depression should not be denied DMPA as a contraceptive choice.

History of long-term use of depot-medroxyprogesterone acetate in patients with cervical dysplasia; case-control analysis nested in a cohort study

Histories of use of depot-medroxyprogesterone acetate (MPA) given by women entering a previously-reported prospective study of risk of cervical dysplasia, including carcinoma, have been evaluated. Over a six-year follow-up period, 348 of the 7199 enrolled women developed cervical dysplasia diagnosed by cytology and confirmed by histology or DNA analysis. Use of MPA prior to entry into the study was reported somewhat more commonly and for somewhat longer periods by the women who developed confirmed dysplasia than by those who did not. However, this association was accounted for entirely by the fact that women who reported use of MPA, particularly at an early age, tended to carry a number of known strong risk factors for dysplasia, specifically, first intercourse at an early age, multiple sex partners and cigarette smoking. These findings indicate that the lack of relationship of MPA use to risk of cervical dysplasia, noted previously for women whose median duration of use within the formal study period was about 2 years, extended to the same women who used MPA prior to the study period—even to those whose duration of prior use was 4 years or more.

Long-acting injectable contraception with depot medroxyprogesterone acetate

Depot medroxyprogesterone acetate (DMPA) is the only injectable contraceptive available in the United States. After more than 20 years of regulatory review, the Food and Drug Administration approved DMPA for contraceptive use in 1992 after the publication of reassuring data about its possible association with breast cancer. It has been used by 30 million women in more than 90 countries. The recommended dosage, 150 mg intramuscularly every 3 months, has a contraceptive efficacy exceeding 99%. After a 150 mg dose, ovulation is inhibited for at least 14 weeks. Almost all users experience menstrual changes, typically episodes of unpredictable irregular spotting and bleeding, particularly during the first year of use. With continued use, spotting and bleeding decrease, and amenorrhea becomes common. Although ovulation suppression may rarely persist for as long as 18 months after the last injection, DMPA does not permanently affect fertility. Long-term DMPA use reduces menstrual blood loss, has been associated with a decreased incidence of candidal vulvovaginitis and pelvic inflammatory disease, and dramatically lowers the risk of endometrial cancer. Prolonged DMPA use may be associated with reversible reduction in bone density, probably related to suppression of endogenous production of estrogen. The most recently published data suggest that long-term use of DMPA induces moderate changes in lipid metabolism that are unfavorable in terms of risk of atherosclerosis. DMPA should be considered a highly effective, safe, convenient, and reversible contraceptive option for appropriately selected patients. (AM J OBSTET GYNECOL 1994;170:1543–9.) Depot medroxyprogesterone acetate (DMPA) is the only injectable contraceptive available in the United States. After more than 20 years of regulatory review, the Food and Drug Administration approved DMPA for contraceptive use in 1992 after the publication of reassuring data about its possible association with breast cancer. It has been used by 30 million women in more than 90 countries. The recommended dosage, 150 mg intramuscularly every 3 months, has a contraceptive efficacy exceeding 99%. After a 150 mg dose, ovulation is inhibited for at least 14 weeks. Almost all users experience menstrual changes, typically episodes of unpredictable irregular spotting and bleeding, particularly during the first year of use. With continued use, spotting and bleeding decrease, and amenorrhea becomes common. Although ovulation suppression may rarely persist for as long as 18 months after the last injection, DMPA does not permanently affect fertility. Long-term DMPA use reduces menstrual blood loss, has been associated with a decreased incidence of candidal vulvovaginitis and pelvic inflammatory disease, and dramatically lowers the risk of endometrial cancer. Prolonged DMPA use may be associated with reversible reduction in bone density, probably related to suppression of endogenous production of estrogen. The most recently published data suggest that long-term use of DMPA induces moderate changes in lipid metabolism that are unfavorable in terms of risk of atherosclerosis. DMPA should be considered a highly effective, safe, convenient, and reversible contraceptive option for appropriately selected patients. (AM J OBSTET GYNECOL 1994;170:1543–9.)

International forum update: depot medroxyprogesterone acetate and endometrial carcinoma.

In response to a recent report (Fam Plann Perspect 11: 47, 1979) that two of 12 rhesus monkeys given 50 times the human dose of depot medroxyprogesterone acetate (DMPA), by body weight, for ten years had developed endometrial carcinoma (CA), a retrospective survey of all hospital admissions for proven endometrial CA in two Thai provinces where DMPA contraceptive injections have been widely used since 1965 was made. From 1974 through 1978, 16 women were hospitalized with confirmed diagnoses of endometrial CA. None of the nine women successfully followed up had previously used oral or injectable contraceptives, nor has the recorded incidence of endometrial CA increased in these provinces. Base on the available evidence, the authors conclude that (a) the data on monkeys given very large doses of DMPA for ten years do not apply to women given normal doses of DMPA for prolonged periods and (b) widespread and long-term use of DMPA can and should be continued.