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Hormonal contraception’s effect on adolescent bone health – Contemporary Obgyn

Case. SL is a 14. 5-year-old girl with heavy periods, dysmenorrhea, and acne seeking menstrual management. Her medical history includes 2 traumatic lifetime upper-extremity fractures plus lactose intolerance. Menarche occurred at 12. 5 years of age and intervals occur every 27 to 32 days, and she routinely misses the few times of school each month because of her bothersome periods. SL takes no medications, including herbal agents or supplements. SL’s mother also had heavy, painful periods as a teen that improved as she got older. She was also recently diagnosed with osteopenia. SL has a boyfriend of 5 months and she confidentially shares that the girl would like contraception “just in case. ” Her mother is open to SL starting a hormonal agent to improve her periods. They ask you what the girl options are.

SL’s story is not atypical. In taking a patient-centered, reproductive justice approach in order to contraceptive counseling, all options should be offered to SL without provider bias. Of course , there are usually many prescribing considerations for any adolescent. Clinicians must assess for healthcare contraindications to contraceptive use while furthermore counseling patients about real estate agent efficacy, potential side effects, confidentiality, access, and ease of and duration of use. Patients plus guardians often ask about the potential long-term effects of contraceptive use on fertility and cancer risk, yet rarely ask about the potential skeletal impacts associated with any given contraceptive. However, clinicians should consider plus discuss what is known about the bone health implications of hormonal birth control method use in adolescence 1-4 given that (1) 40% in order to 60% associated with one’s adult bone mass is accrued in adolescence; (2) the 10% increase in bone mass accrual during adolescence can potentially reduce adult fracture danger by 50%; and (3) Medicare cost estimates in the United States related to adult osteoporosis and fracture care exceed $50 billion dollars annually, including indirect costs such as productivity loss and caregiving. 5

Bone Physiology and Assessment

Collagen and noncollagenous proteins form an organic matrix upon which bone tissue mineral, composed primarily of calcium plus phosphate, is deposited to form bone. Osteoblasts, osteoclasts, and osteocytes are the cells responsible for forming plus resorbing bone fragments, as bones grow in length and diameter, increase in bone mineral density (BMD), change shape, and respond to the particular daily insults of childhood and teenage years, an overall process known as bone remodeling. 6 Bone bulk (BM) has the potential in order to accrue throughout childhood and into young adulthood to a genetically determine peak bone tissue mass (PBM), at which time the skeleton has reached its adult type and a stable state associated with bone nutrient content. While 60% to 80% of one’s possible PBM is genetically predetermined, there are extrinsic factors that will can negatively impact attaining optimal PBM, including chronic illness, medication exposure, substan ce use, physical inactivity, nutritional deficits, plus abnormal hormonal milieu. 7, 8

Maximal rates of BM accrual occur during the particular dynamic phase of puberty associated with peak height velocity driven by multiple hormones including, but not limited to, sex steroids, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Estrogen will be particularly influential with estrogen receptors found on all skeletal cell types. Estrogen promotes the survival of osteoblasts, the bone fragments building cells, and has a pro-apoptotic impact on osteoclasts, the cells responsible for bone resorption. Net BM accrual depends on the balance between formation plus resorption. During adolescence, bone tissue formation ought to exceed bone fragments resorption. It is suggested that simply by late age of puberty, over 90% of one’s PBM offers been attained. seven Notably, female also influences the pubertal growth spurt via the
GH/IGF-1 axis as well because growth plate closure and the cessation of linear growth. 9 Given the importance of estrogen in bone physiology, any conditions or treatments altering physiologic female production can negatively impact bone wellness.

The best clinical indicator of bone tissue health is usually fracture history. Individuals with a history associated with fracture resulting from low-impact mechanisms of injury should raise concern for skeletal fragility and warrant a bone health evaluation. While adolescent fractures are not uncommon, along with risk estimates ranging from 6% in order to 40% with regard to girls up to aged 19 years, few pediatric studies evaluate break incidence like a primary study end point. 10, 11 Dual-energy x-ray absorptiometry (DXA) is the clinical plus research tool most commonly used to evaluate BMD, acting being a surrogate marker of bone health. An adolescent’s BMD, while measured by DXA, is definitely compared to the normative database of age- and sex-matched peers to generate a Z-score. A Z-score associated with 0 suggests average BMD for age group, while the Z-score of –2. 0 or less means that the adolescent’s BMD can be 2 or even more standard deviations lower than the average BMD associated with age- and sex-matched peers in the comparative database. BMD accounts for the particular majority of bone strength with the primary cause of grownup osteoporotic bone fracture being reduced BMD through age-related bone fragments loss and/or a failure in order to achieve optimal PBM simply by young adulthood . twelve

Unlike measures of height and weight, obtained frequently in child years and teenage life, BMD steps by DXA are not routinely tracked over time inside otherwise healthy individuals. Therefore, for most healthful children plus adolescents it is not really possible to know their BMD trajectory toward their own PBM. Importantly, per the International Society for Clinical Densitometry, “In patients with primary bone disease, or at risk for secondary bone disease, a DXA must be performed when the patient may benefit from interventions to decrease their elevated risk associated with a clinically significant crack, and the particular DXA results will influence that administration, ” meaning a DXA is warranted only if the results will inform clinical decision-making. 13

Hormonal Contraception and Bone

The risks and benefits associated with the medical care we provide need to be weighed and discussed with individuals and, when appropriate, with their caregivers. From a pure bone tissue health perspective, allowing the body to do what the body naturally does best will be physiologically ideal. This includes supporting a normally functioning hypothalamic-pituitary-ovarian (HPO) axis. Many junk contraceptive brokers prevent pregnancy and/or alter menstrual patterns by altering this HPO axis. Consequently, such hormonal contraceptive providers have the potential to adversely impact BM accrual within adolescence. Scientifically determining this kind of impact is certainly challenging upon multiple levels given numerous available plus changing contraceptive formulations, variable contraceptive adherence with time, regularly needed confidentiality in adolescent care, confounding extrinsic impacts on bone fragments, and the inability to randomize and make use of placebo controls in young contraceptive research. Therefore , available evidence must be interpreted in light of these limitations. Contraceptive choices discussed will focus on what is recognized regarding their particular bone wellness impacts, which in no way is meant in order to diminish the significant roles these real estate agents play in adolescent and adult reproductive health treatment. There is nothing more important than providing an individual with the particular tools they desire along their reproductive system health journey, including menstrual management plus contraception. It can also be argued that will preventing the psychosocial effects and identified BM loss associated along with 1 or even more pregnancies and breastfeeding in the particular adolescent many years may far outweigh any kind of negative bone impacts of contraceptive agencies themselves.

Depot medroxyprogesterone acetate

Depot medroxyprogesterone acetate (DMPA) may be the only hormonal birth control method agent with a black box warning from the US Food and Drug Administrative regarding its adverse effects on bone tissue. 14 This warning was informed by several studies demonstrating BM reduction during DMPA use . 15-19 The particular BM loss associated along with DMPA is attributable primarily to its effects on the HPO axis resulting in a marked hypo-estrogenic state resulting in increased osteoclast activity at the level associated with bone. Interestingly, DMPA will be also thought to bind to bone glucocorticoid receptors, thereby decreasing osteoblast proliferation. 20 The overall effect favors bone resorption over formation, which is usually counter in order to normal teenage bone physiology. Of note, studies show that BM loss is definitely most significant within the first year of usage and can be at least partially reversible following DMPA cessation. 21, 22 In older adolescents and grownup women who have achieved or nearly achieved PBM, this is certainly reassuring. Nevertheless, in younger adolescents tasked with gaining considerable BM over a number of years, the particular implications of BM reduction on future PBM potential are likely more significant. This is unlikely that more youthful adolescents treated with DMPA regarding prolonged periods of time attain their genetically established PBM following cessation associated with DMPA. In regard to fracture danger, in a case-control research of mature DMPA users, there was an association among fracture and prolonged current and prior DMPA use; however, similar studies have not be conducted in children who have very different bone fragments physiology. 23 Despite such concerns, an individual’s DMPA make use of should not be time-limited if this is the best option for them and there is no formal recommendation to assess bone density in DMPA users. 24 Lastly, in a convenience sample of older adolescents and young adults with cerebral palsy, there was no difference in BMD Z-scores by DXA in those with plus without DMPA exposure. The authors concluded that this population with known BMD issues should not really be denied access to DMPA if it is usually your best option intended for them per patient-centered decision-making—a relevant conclusion for all patients. 25

Contraceptive Implants and Hormonal Intrauterine Devices

There have been couple of studies concerning the bone health impacts of long-acting, reversible contraceptive (LARC) methods in children. Cromer et al prospectively assessed vertebral BMD changes in teenagers controls (n =17) plus users of the NORPLANT implant system (n = 7) at 1 year and again at 2 years (n = 4 regulates, n sama dengan 3 Norplant users). 15 Both groups were of comparable age (15. 2 yrs vs 15. 5 years for Norplant users and controls, respectively). Reassuringly, BM accrual has been similar over time in both groups. The particular authors propose that estrogen levels are not suppressed as much along with this birth control method implant as they are with DMPA. Such an estrogen threshold hypothesis has been supported by several studies plus reviewed simply by Hadji ainsi que al in a paper regarding the bone health associated with progestins. 26 Additional studies evaluating the 68-mg etonogestrel implant Implanon and the 75-mg levonorgestrel implant Jadelle was primarily carried out in adults. Evidence recommended a reduction in BMD in the midshaft ulna with BMD stability on the distal radius more than 18 months associated with implant use. 27 When comparing BMD change within adult women with Implanon vs the nonhormonal intrauterine device (IUD), there were gains in BM both in groups at the spine. Mean estradiol levels had been notably higher within the Implanon cohort at all measured time points over two years. This is reassuring whenever considering how important estradiol is for BM accrual in adolescence. It will be important in order to note that routine clinical practice recommendations do not include obtaining DXA scans or estradiol amounts in implant users.

There are no research of the particular BMD influences of junk IUDs in adolescents. Junk IUDs carry out not significantly suppress endogenous estrogen production. The amenorrhea that is usually frequently accomplished with hormonal IUDs is definitely likely secondary to direct endometrial results rather compared to significant HPO axis suppression. = In a cross-sectional study of adults using the 52-mg levonorgestrel IUD Mirena, there was clearly no distinction in forearm BMD compared with adults using a nonhormonal IUD. twenty-seven In this same cohort followed prospectively, forearm BMD was stable as time passes. 24 Significantly, in case-control analysis, there is simply no association in between hormonal IUD use plus fracture, and some evidence supports a reduced fracture risk in junk IUD customers. 29, 30

Progestin-Only Pills

The bone tissue health effect of progestin-only pills (POPs) in adolescents is similarly understudied. Once again, referring to the estrogen threshold speculation, POPs probably do not suppress the HPO axis enough to lower female levels below a threshold that would be harmful to bone. 26 That said, whether a young teen would accrue as much BM upon POP therapy in contrast to zero therapy in all can be unknown. Importantly, there are no recognized associations between fracture incidence and POP use. 29

Combined Hormonal Birth control method Agents

Combined hormonal contraceptives (CHCs) similarly exert their contraceptive and monthly management affects by changing the HPO axis, resulting in suppression of endogenous ovarian estradiol production, although not to the extent that DMPA does. Additionally , combined oral birth control method (COC) make use of negatively effects the liver’s production associated with IGF-1 and is related to elevated biological markers of bone resorption. 31, 32 The demonstrated impact associated with CHCs on adolescent bone fragments health is definitely challenged by multiple obtainable drug formulations and a lack of randomized, placebo-controlled trials. In addition , studies are usually flawed by the fact that will control groups are often young than subjects on COCs, and early adolescent bone physiology is usually drastically different from that of later teenage years, making meaningful conclusions regarding BM change between cases and controls difficult. All totaled, studies and systematic reviews suggest that treating adolescents with COCs containing ≥ 30 μg ethinyl estradiol (EE) may support bone tissue health better than low-dose (≤ 2-μg EE) pills. fifteen, 19, 30, 32-36 Additionally , the greatest impairment of COC use on BM accrual can be thought to be within the first few many years following menarche when BM accrual is certainly most important. thirty-two, 37 Of note, within a large retrospective study of ladies from the United Kingdom along with COC make use of, fracture incidence was lower in those that had used COCs compared with those who had not, and longer duration associated with COC use was associated with lower
stress fracture incidence. 38

Very few studies have evaluated the bone fragments health influences of contraceptive patches plus vaginal rings. Massaro ou al assessed spinal BMD in younger adult females using a contraceptive patch (norelgestromin 150 µg and
EE 20 µg) vs a vaginal ring (etonogestrel 120 µg with EE 15 µg) and found no substantial change in BMD over one year within either group. 39 The pilot research with 5 adolescents making use of the birth control method patch and 5 likewise aged settings found no change in BM more than 1 year in the patch users in comparison with the nearly 4% increase within total-body bone mineral content in settings. 40 IGF-1 levels were notably the particular same within the patch users compared with the controls.

Optimizing Bone Health

Regardless of contraceptive used, all clinicians ought to be counseling children to optimize their bone tissue health. Including engaging in weight-bearing activity as is possible; avoiding substance use; and having a healthy, adequate, plus well-balanced diet. Very couple of adolescents achieve the recommended daily allowance (RDA) to get calcium and vitamin D. 41 A healthy individual will maintain blood calcium levels inside a normal range in the expense of their bone denseness if they are not really ingesting adequate calcium or are unable to adequately absorb the calcium they do ingest as a result of vitamin D deficiency. The RDA pertaining to calcium is 1300 mg daily meant for 9 in order to 18-year-olds, which is slightly more than four 8-ounce glasses of milk each day. Since calcium is not easily absorbed in large quantities (up to 500 mg will be absorbed from a time), intake must also be spread throughout the particular day, whether through dietary intake or even supplements. Reviewing the Center for Young Women’s Wellness resource on calcium intake with patients and families can be eye-opening. Similarly, it is very hard to meet the RDA for vitamin D through diet alone, which is why vitamin D deficiency is common. 42 Although there are no recommendations to check calciferol levels in otherwise healthy individuals, meeting the RDA for vitamin D is necessary to support overall adolescent bone health, and some individuals may need more than the RDA to achieve vitamin D sufficiency. 43

After reviewing her options, SL is most interested in pursuing a hormonal IUD for menstrual management and for contraception when she needs it. Her mother was concerned about the potential bone wellness impacts of the other contraceptive agents given her own diagnosis of osteopenia. SL likes that she wouldn’t have to remember to take a medication. Given her lactose intolerance, she avoids dairy, and after reviewing the youngwomenshealth. org website, the girl and the girl mother plan to incorporate more calcium and vitamin D into her diet and/or through supplements to aid healthful bones.

Conclusion

Optimizing child plus adolescent bone health can reduce morbidity and mortality associated with adult osteoporosis, so considering and discussing bone health with adolescents is essential. Unfortunately, it is challenging to fully understanding the impacts of all available hormonal contraceptives on adolescent bone tissue health given inherent limitations in research to date, yet it really is our job in order to use available evidence to inform our patient-centered approach to reproductive wellness care.

The following key points should be considered:

DMPA is associated with BM loss during use. Prolonged use in the first few years following menarche could have the greatest negative impact on bone. It is reassuring that there is substantial BM recovery following DMPA cessation; however , prolonged use in younger adolescents may impair PBM. Prolonged DMPA use may also be associated with adult fracture.

POPs and hormonal IUDs do not substantially suppress the HPO axis plus therefore are thought to have no ill effect about BM, although studies within adolescents, especially young children, are not available.

Hormonal implants are generally thought to be safe for bone, even though whether a young adolescent would reach their genetically determined PBM while using a contraceptive implant is not known.

Individuals making use of COCs possess demonstrated BM gain during adolescence, although such accrual may be less than what they would have seen without COC treatment. When used, a COC containing ≥ 30 µg EE is likely preferred, if tolerated, from a purely bone health perspective. There is too little evidence regarding the bone tissue impact of vaginal rings and contraceptive patches in adolescents to inform
the recommendation.

Engaging in weight-bearing activities as will be feasible and ingesting adequate nutrition including meeting the particular RDA with regard to calcium plus vitamin D intakes are important regarding all adolescents.

The birth control method agent that is best intended for a given adolescent is the 1 that they prefer once they have got been informed about their use, efficacy, side effects, and risks, and once issues of access, confidentiality, and medical eligibility have been considered. Such information can be overwhelming for patients and caregivers. Clinicians are tasked with the important job of conveying this information in an understandable way without personal bias to support adolescents along their reproductive health care journey.

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