measured on a thumb, the nymph is 2mm IntroductionLyme disease was fi rst described in the USA in 1974 available from the Health Protection Agency (HPA)2 and takes its name from Old Lyme in Connecticut, Lyme Borreliosis Unit based at Southampton General where the fi rst outbreaks were noted. The illness had been known by a variety of names in Europe since the
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The Long-term Health Implications of Depo-Provera
Edra Spevack, ND The reproductive health of adolescents and young indicate a correlation between DMPA use and an adults is a major determinant of their future well-being. increased risk of fracture and HIV infection. These While Depo-Provera, or depot medroxyprogesterone results have intensified concern about whether the ben- acetate (DMPA), is highly effective at preventing preg- efits of DMPA outweigh the long-term risks. This paper nancy, mounting evidence suggests that its side effects reviews the health implications of DMPA and recom- may have a negative impact on long-term health. mends alternative contraceptive methods that may have Together with mood changes, weight gain, menstrual more favorable outcomes.
irregularities, and delayed return to fertility, recent data Corresponding author: Edra Spevack, ND Depo-Provera Adverse Effects
E-mail address: [email protected] Compared to other progestin-only contraceptives, DMPA contains substantial y higher levels of progestin.5,7 A 90-day dosage of DMPA adds up to 150 mg,5 signifi- Depo-Provera Use and Demographics
cantly higher than the 90-day dosages of the progestin- Currently, the combination (estrogen and progestin) only pill (POP) (31.50 mg), Mirena IUD (1.8 mg), and oral contraceptive pill (OCP) and condom are the most Implanon/Nexplanon (etonogestrel implant) (6.3 mg). common contraceptive methods used by teenagers.1 In Consequently, DMPA is associated with more side effects, cases where women are at an increased risk of estrogen including irregular menstruation, anxiety, headaches, complications, however, progestin-only hormonal contra- weakness, fatigue, bloating, abdominal pain, and weight ception is often prescribed as the method of choice. This gain (almost 10 pounds in 2 years).5,7 Additional y, many practice applies to women who are breastfeeding or have users experience delays in fertility (up to 18 months) fol- an increased risk of forming blood clots as well as those lowing discontinuation. DMPA usage is also directly who have experienced complications on estrogen-contain- linked to amenorrhea in 70% of users after 2 years. Along ing contraceptives.2 One of the progestin-only methods, with these common side effects, recent data revealed an Depo-Provera (DMPA), was original y approved to allevi- increased risk of fracture caused by the DMPA-induced ate endometriosis and certain cancers and is currently lack of estrogen over extended periods of time, particu- most commonly used as a contraceptive.3 More than 2 larly in women who have not yet attained peak bone million women in the United States, including approxi- mately 400 000 adolescents, are using DMPA annual y as FDA Black Box Warning
The benefit of DMPA relates to the fact that it is (1) In 2004, the Food and Drug Administration (FDA) 99% effective at preventing pregnancy when used proper- responded to concerns regarding fracture risk and the ly; (2) requires only one injection every 3 months; and (3) potential of developing DMPA-induced osteoporosis by offers extended protection due to the crystallized proges- issuing the following black box warning13: tin that slowly dissolves into the bloodstream.2,3,5 According to James Trussell in his chapter "Contraceptive Efficacy" Women who use Depo-Provera Contraceptive Injection may in Contraceptive Technology: Nineteenth Revised Edition, lose significant bone-mineral density. Bone loss is greater "The typical failure rate of DMPA is 0.3 per 100 woman- with increasing duration of use and may not be completely reversible. It is unknown if use of Depo-Provera Contraceptive years, which is comparable with that of implantable con- Injection during adolescence or early adulthood, a critical traceptives, copper intrauterine devices (IUDs), and surgi- period of bone accretion, will reduce peak bone mass and cal sterilization."6 Although the condom is the only meth- increase the risk for osteoporotic fracture in later life. Depo- od that offers protection from transmission of sexual y Provera Contraceptive Injection should be used as a long- term birth-control method (eg, longer than 2 years) only if transmitted infections (STIs) and is 98% effective when other birth-control methods are inadequate.
used properly, prescribers tend to rely on hormonal meth- ods that are less dependent on users' compliance.6 Integrative Medicine • Vol. 12, No. 1 • February 2013 This article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1543953X. To subscribe, visit imjournal.com
reversal of Bone Density Does Not Guarantee use of one to two, three to nine, or 10 or more DMPA
prescriptions yielded adjusted OR for fractures of 1.18 Although the FDA's warning had an impact on pre- (95% CI = 0.93-1.49), 1.36 (95% CI = 1.15-1.60), and 1.54 scription trends, some studies have offered reassurance, (95% CI = 1.33-1.78), respectively." Fracture risk was exac- indicating that the DMPA-induced bone loss is at least par- erbated by the length of use (>2-3 years) regardless of tial y reversible fol owing the discontinuation of whether a user was under or over the age of 30.9 injections.10,14,15,16 Consequently, DMPA remains a common Evidence indicates that continued use of methods prescription, often used as a contraceptive for sub-Saharan that combine estrogen and progestin following the discon- African women as wel as young African American and tinuation of DMPA interferes with the reversal of bone Native American women who are in their formative years loss.29 Therefore, it is possible that any interventions that prior to reaching peak bone mass.17 Building peak bone affect normal hormone levels may negatively impact bone mass usual y occurs from preadolescence until approxi- integrity, especial y when used prior to attaining peak mately age 30.18 This prescription trend is socioeconomi- bone mass.30 This recent research underscores the need to cal y driven and reflects a heightened concern for the per- determine the lifetime risk of fracture following DMPA sonal and public health impact of unplanned pregnancies in use, and it suggests that exploring contraceptive approach- these populations. Moreover, given the low socioeconomic es that minimize the need for hormonal interventions in status of women in these demographics, DMPA tends to be young people would be prudent.9 prescribed as a cheaper alternative compared to other con- The Long-term Impact of Osteoporosis
Until this point, using dual-energy, x-ray absorptiom- Although studies indicate that DMPA reduces BMD etry to determine bone-mineral density (BMD) has been and increases the likelihood of fractures during usage, the the method of choice for assessing the influence of DMPA long-term influence of DMPA following discontinuation on bone health. A reversal of bone loss, however, does not has not been established. Given that the drug was approved guarantee safety from fracture and secondary osteoporosis. as a contraceptive in 199231 and osteoporosis is predomi- Although low BMD is associated with fracture risk, it is only nately a postmenopausal illness, determining a DMPA- one determinant,19-25 and in reality, most fractures occur in associated influence on the development of osteoporosis individuals with a moderate BMD.19,26 Evidence suggests has proven difficult. Prescribers, however, must consider that together with BMD, both bone quality and turnover all potential eventualities. DMPA may undermine the contribute to bone strength and are important in determin- long-term health of individual users and exacerbate the ing the risk of fracture. As a result, the Fracture Risk health care burden associated with osteoporosis-related Assessment Tool (FRAX) was developed and is currently sequelae. Moreover, to assess the risk-to-benefit ratio of used with BMD as a more comprehensive assessment of DMPA adequately, it is imperative to understand the long- fracture risk in older populations. No such assessment is term implications of osteoporosis ful y. used to calculate fracture risk in younger hormonal contra- The mortality and morbidity associated with osteopo- ceptive users. Similarly, studies designed to determine the rosis is substantial. The lifetime risk of fractures is 40%, influence of DMPA on bone health do not account for frac- equal to the risk of cardiovascular disease.19,32 After the age ture risk variables other than BMD. of 50, approximately 1 in 3 women will experience an A 2010 systematic review by Unnanuntana et al con- osteoporosis-related fracture.19,33,34 Following a hip frac- firmed that altered bone metabolism, whether induced by ture, as many as 20% will die in less than a year, and 50% drugs or il ness, contributes to the occurrence of fragility will require assistance with walking.19,35 The pain and fractures. More specifical y, Unnanuntana et al concluded deformity resulting from osteoporosis limit the range of that a balance between bone resorption and formation is functional activities required for independent living. This critical to preventing microdamage and maintaining the debilitation often leads to depression and anxiety about structural integrity of bone.27 Therefore, the rapid rate of leaving home. Consequently, many individuals with osteo- bone formation following discontinuation of DMPA sug- porosis become dependent on the help of others and often gests the possibility of an increased risk of fracture regard- require nursing-home care.19,36 less of the level of BMD attained. Consequently, the safety Together with the human cost, osteoporosis places an of DMPA can only be definitively determined by measuring exorbitant financial strain on the health care system. Each the long-term incidence of fractures fol owing use. year, $14 billion is spent on 1.5 million osteoporosis-relat- While the field lacks substantive information regard- ed fractures.19,35 Currently, complications associated with ing the correlation of DMPA with fractures,28 recent osteoporosis necessitate longer hospital stays than other research has demonstrated that DMPA is associated with a diseases, including diabetes, myocardial infarctions, and slight, statistical y significant risk of fracture in 20- to breast cancer.37 By 2050, the worldwide incidence of frac- 44-year-olds. Meier et al "identified 17 527 incident frac- tures in women is expected to increase by 240%.38 This ture cases and 70 130 control patients (DMPA exposure: fact, combined with the disease's psychological and finan- 11 and 8%, respectively). Compared with nonuse, current cial costs, makes the prevention of osteoporosis essential.19 Integrative Medicine • Vol. 12, No. 1 • February 2013 This article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1543953X. To subscribe, visit imjournal.com
While unintended pregnancies in young adults and low- The World Health Organization (WHO) met in income populations have serious consequences, the pos- January 2012 to respond to the potential link between sible influence of DMPA on the development of osteopo- DMPA use and HIV transmission.40 The WHO recom- rosis cannot be ignored.
mended that the guidelines be modified to emphasize the importance of using condoms concurrently while on hor- DMPA-induced HIv risk
monal contraceptives. The organization resisted amend- Together with the potential for increased fractures, ing prescription trends, however, stating that the hor- new evidence has led to even greater concerns about monal link has not been proven.42 health risks associated with DMPA use. A recent study Yet current research in the area of vaginal immunol- published by The Lancet, examining contraceptive use in ogy has confirmed the protective role of the hormonal y sub-Saharan African women, revealed that DMPA dou- regulated epithelial lining,43 cervicovaginal secretions,41,44 bled the risk of both contracting and transmitting HIV.39,40 and vaginal microbiota.41,43 Furthermore, the female repro- The study investigated serodiscordant couples (ie, one ductive tract's immune system provides both innate and partner is HIV positive, and the other is HIV negative) adaptive immunity that is also tightly regulated by the and found that "women using hormonal contraception cyclic shift in estrogen and progesterone levels.41,45,46 became infected at a rate of 6.61 per 100 person-years, Ample evidence indicates that hormonal contraceptives compared with 3.78 for those not using that method. interfere with these natural defense mechanisms.38,43,46 Transmission of HIV to men occurred at a rate of 2.61 per Given that the hormonal environment at the time of infec- 100 person-years for women using hormonal contracep- tion determines a female's susceptibility and predisposi- tion compared with 1.51 for those who did not."39,40 These tion to infection,47,48 these disturbances to contraceptive findings are particularly concerning given that the major- users' immunophysiological systems come with inherent ity of women who are prescribed DMPA are also at an risks. increased risk of contracting HIV.39,41 Accordingly, several plausible, evidence-based expla- While this Lancet publication exceeds other similar nations for the increased risk of HIV infection in DMPA investigations in design, five of the most rigorous, pro- users exist. DMPA dramatical y decreases estrogen, which spective observational studies also indicated an increased causes a simultaneous reduction in both the vaginal lacto- risk of HIV infections associated with DMPA-induced bacilli levels as well as the thickness of the glycogen, vagi- physiological changes. The exact mechanism is unknown; nal epithelial layer. Lactobacilli are healthy bacteria that however, theoretical y the DMPA could influence the normal y thrive in the vagina under ideal conditions and integrity of the vaginal-cervical epithelium, directly protect against infections by maintaining pH levels and increase the virulence of the virus, and/or cause shifts in producing H O . Researchers have suggested that the local immunology.39 Irrespective of the cause, researchers DMPA-induced microbiota disturbances, together with were able to establish higher concentrations of HIV in the thinning of the glycogen vaginal epithelial layer, may genital fluid of those infected with HIV while using compromise the vaginal barrier and predispose users to DMPA injections.40 Studies on Macaques supported these infection.43 These findings have added substantial weight findings by demonstrating that DMPA increased the risk to the concern about prescription practices for DMPA, of acquiring various strains of simian immunodeficiency given that a high proportion of HIV-exposed women are virus.39 The simian studies also demonstrated a DMPA- resistant to infection, and many researchers have argued associated rise of virus in the blood and increased viral that transmission most likely occurs in cases of vaginal shedding in the genital tract.39,41 epithelial atrophy or damage.49 These findings also have Although the recent human study was restricted to supported the evidence that HIV infection is significantly African subjects, the investigators stated that the findings higher in women lacking H O -producing lactobacilli, as can most likely be generalized to all populations. is often the case in DMPA users.41,50 Considering that the majority of the 16 million women Furthermore, changes in the cervicovaginal fluid of currently infected with HIV are living in sub-Saharan DMPA users, including an increase in inflammatory Africa, however, researchers are particularly concerned cel s41,51 and a decrease of protective immunomodulatory about these populations.40 Promoting DMPA as a contra- factors, such as natural antibodies41 and the secretory leu- ceptive for women who are underresourced, and/or who kocyte protease inhibitor,52 is also of fundamental impor- live in countries with a high prevalence of HIV infections, tance. These protective factors might play a role in pre- could contribute to the HIV epidemic. Isobel Coleman, venting the transmission of HIV infection.41 Additional y, director of the Women and Foreign Policy Program at the the increased accessibility of primary target cel s, such as Council on Foreign Relations, expressed her concern, stat- Langerhans cel s,41,49,53 in the vaginal epithelia and stroma ing "if it is now proven that these contraceptives are help- of DMPA users could potential y elevate the risk of acquir- ing spread the AIDS epidemic, we have a major health ing HIV.54 crisis on our hands."40 Although correlations between DMPA-induced immunophysiological changes and increased risk of HIV Integrative Medicine • Vol. 12, No. 1 • February 2013 This article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1543953X. To subscribe, visit imjournal.com
infection have been established, a great deal of controversy argument for promotion of DMPA in underserved popu- exists surrounding this issue based on the fact that DMPA lations and countries with a high prevalence of unplanned is highly effective at reducing unplanned pregnancies. pregnancies is that the benefits outweigh the risks. Advocates argue that the number of women who are able McGouph and Bigrigg, however, validated the need to to avoid HIV infection does not justify risking the much revisit these prescribing patterns by establishing that higher number of women facing unplanned pregnancies DMPA significantly decreased BMD in a group of under- and the associated deaths that might result from limiting resourced, long-term users.60 Moreover, the potential, far- the prescription of DMPA. Still others believe the recent reaching implications of promoting DMPA as a contracep- Lancet publication warrants switching DMPA users to tive in underresourced populations and developing coun- lower-risk methods, such as the IUD or sterilization.55 tries is substantiated by the significant increases in HIV Based on her 2003 review of the influence of hor- transmission and infection that may be associated with monal contraceptives on the immune system, Brabin has usage.39,40 cautioned that clinicians who prescribe contraceptives to Together with Stephen Lewis, former UN Special patients at high risk of STIs, particularly HIV, require a Envoy on AIDS in Africa, Paula Donovan—head of the more comprehensive understanding of the implications.47 international HIV advocacy organization, AIDS-Free Consequently, although not yet definitive, the recent find- World, and former East and Southern African advisor for ings associating DMPA with a heightened risk of contract- UNICEF—expressed her concern for the WHO's response ing and transmitting HIV must be explored further before to the recent findings associating the potential link of discounting the influence of DMPA on the HIV epidemic. DMPA to HIV transmission. She criticized WHO for their Furthermore, it would be prudent to reevaluate WHO's delay in responding to the results and publicly stated that response to these findings. At a minimum, condoms their recommendations were not transparent and caution- should be distributed and probiotics and vaginal estrogen ary, thus reducing the public's ability to make well-in- creams concurrently prescribed to help bolster the vaginal formed decisions. She also cautioned that verbal state- immunity of DMPA users and decrease their risk of infec- ments recommending concurrent condom use will likely tion. Additional y, vaginal phytoestrogen creams are a have little influence on behavioral change compared to potential nonhormonal alternative to estrogen cream providing a supply of condoms with DMPA and hormonal prescriptions.61 These issues highlight the fact that social and racial disparities in prescribing practices may influ- controversial Prescribing Practices
ence the quality of health care in developing countries and Potential racial and socioeconomic disparity in doc- tors' prescription practices regarding DMPA has also In response to the DMPA-associated HIV findings, 40 caused considerable controversy. Currently, the majority women met in East Africa to clarify women's needs with of users are from minority and low-income populations.17,56- respect to hormonal contraception and reproductive 58 Approximately 6% (12 million) of sub-Saharan African health care and prepared a summary for the UN's sched- women between the ages of 15 and 49 use DMPA injec- uled technical consultation. The women included research- tions as a contraceptive.40 DMPA use is considerably lower ers, medical professionals, women's rights advocates, HIV in the United States. The Center for Disease Control's and reproductive-health counselors, and activist women National 2006-2008 Survey of Family Growth indicated living with HIV in Rwanda, Zimbabwe, Uganda, South that 22.2% of women between the ages of 15 to 44 used Africa, Kenya, and the United States. After just half a day DMPA at one time and 2% were currently using DMPA.59 of discussion, they reached a consensus, including62: The drug, however, is disproportionately prescribed to minority and low-income women. According to the It is not sufficient to say that the data are mixed, and we need Committee on Women, Population, and the Environment more research … Clear information must be provided now on (CWPE), "In a recent study of Depo users in the US, 33% the potential risks of both hormonal contraceptive use and pregnancy. Women need clear and balanced information on were under the age of 19, 84% were black women, and 74% what is known and unknown. Women will not be divided by were low income."17 issues of various risks—the response cannot pit contracep- These trends reflect the fact that DMPA is prescribed tives versus maternal mortality. We don't accept an either/or as a means to address low compliance, which health care approach. Both problems need to be addressed.
clinicians often associate with low-income populations, The following organizations oppose the use of Depo- including young women in developing countries. Provera; the list is not exhaustive17: (1) Black Women's Unfortunately, this population frequently lacks the sex Health Imperative; (2) The National Latina Health education offered in more affluent schools and countries. Organization; (3) The Native American Women's Health Furthermore, while users may have a cursory understand- Education Resource Center; (4) the National Women's ing of the side effects, they are often unaware of the long- Health Network; (5) the Women's Economic Agenda term implications of DMPA use, thus diminishing their Project; (6) the Women's Health Education Project; (7) ability to make well-informed choices.17,56-58 The primary Committee on Women, Population, and the Environment; Integrative Medicine • Vol. 12, No. 1 • February 2013 This article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1543953X. To subscribe, visit imjournal.com
Table 1. Integrative Medicine's Contraceptive Recommendations
Probiotic: oral capsules/powders and vaginal suppositoriesa Calcium;b vitamin Db (or safe sun exposure); magnesium supplement; combined with diet, calcium daily dosage of 1000-1500 mg depending on age and type of contraceptive.
Phytoestrogen or estrogen creamc Calcium-rich nutrients (organic): kelp; dulse; almonds; tofu; dark, leafy greens; yogurt; feta cheese; goat cheese; salmon and sardines with bones; blackstrap molasses; tahini and sesame seeds; etc.
Other nutrients to be considered (ideal y through dietary intake): zinc, manganese, boron, copper, B , vitamin C, vitamin K, CoQ10, and silicon.
Phytoestrogen-rich foods: unprocessed soy, fermented soy, and ground Phytoestrogen-rich foods: unprocessed soy, fermented soy, and flaxseeds (theoretical benefit)d ground flaxseeds.d Phytoestrogen herbs: Pueraria mirifica, Saururus chinensis (theoretical Phytoestrogen herbs: Pueraria mirifica, Saururus chinensis.e benefit)eEssential fatty acids (omega-3) (theoretical benefit)f Essential fatty acids (omega-3).fRecommend avoidance of excess alcohol, b tobacco,b caffeine, carbon- ated sodas, red meat, salt, excess fluoride, and other substances that interfere with bone health.
Sauna/sweat therapy.g Healthy diet: minimize exposure to heavy metals, pesticides, and xen- obiotics to avoid exacerbating compromised bone integrity.
Note: These treatments may be useful for current and recent users of hormonal and IUD contraceptives.
aProbiotics: A growing body of evidence supports the use of probiotics in the prevention and treatment of urogenital infections as well as in the enhancement of immunity. Li et al recently published an article, "The Importance of Vaginal Microbes in Reproductive Health," stating, "The use of probiotic lactobacilli vaginal y and oral y has shown great promise in helping to restore and maintain a healthy vagina, and studies have shown that certain strains have the capacity to interfere with…inflammatory pathway[s]…"72 cPhytoestrogen cream: While the research is limited, two clinical trials have supported the use of a gel containing hyaluronic acid, liposomes, phytoe- strogens from Humulus lupulus extract, and vitamin E for the relief of atrophic vaginitis. These studies demonstrated improvement of vaginal atrophic symptoms without the side effects that are commonly attributed to hormonal creams.73 dPhytoestrogen foods (isoflavones and lignans): "Phytoestrogens have a similarity in structure with the human female hormone 17-β-estradiol, which can bind to both alpha and beta estrogen receptors and mimic the action of estrogens on target organs, thereby exerting many health benefits when used in some hormone-dependent diseases."74 An animal study using ovariectomized ewes demonstrated an improved clearance rate of progesterone.75 "Dietary intake of these so-called phytoestrogens has been associated with positive effects on menopausal complaints, hormone-related cancers, and ePueraria mirifica and Saururus chinensis: P mirifica was found to have an osteogenic effect on bone in ovariectomized rats, and a recent study con- firmed these findings by demonstrating the herb's influence on estrogen-receptor-dependent osteoblast differentiation rather than proliferation.77 "It was concluded that S chinensis treatment could prevent ovariectomized-induced loss of bone mass and deterioration in trabecular microarchitecture by suppressing bone turnover, thereby maintaining bone structural integrity. Furthermore, no stimulation or proliferation of uterine tissue was noted."78 Given that S Chunensis interferes with bone turnover, future research might explore the intermittant use of the herb. This approach could theoretical y support bone remodeling.
fEssential Fatty Acids: Omega-3 in a higher dose with respect to omega-6, helps to protect bone mass by preventing the formation of osteoblasts.79 A recent study demonstrated that omega-3 in combination with aerobic exercise was synergistic in decreasing inflammation and increasing BMD.80 Another study showed a positive correlation between omega-3 (DHA + EPA) and BMD in postmenopausal Korean women.81 gSauna/sweat therapy: Bone and adipose tissue are storage sites of xenobiotics and xenoestrogens. Consequently, exposure may influence bone integ- rity. Sweating assists with decreasing the xenobiotic load. Additional y, unpublished data from the prospective 1999 Toronto Osteoporosis Prevention Study, which investigated the influence of lifestyle factors on BMD in 669 Caucasian women aged 18-35, revealed a slightly significant correlation between increased BMD and sweating as an independent variable.
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(8) INCITE! Women of Color Against Violence (9) Furthermore, any contraceptive method that causes Communities Against Rape & Abuse (CARA); and (10) disruptions to normal physiology requires a means to the Canadian Coalition on Depo-Provera. A number of address its side effects. Accordingly, complementary and scientists and women's associations in India are opposed alternative medicine (CAM) is strongly indicated to allevi- to DMPA usage.63 India removed DMPA from its Family ate potential y compromised bone as well as vaginal health Planning Protocol in 2002.
(Table 1). The FDA states, "Although no studies address whether calcium and vitamin D may lessen BMD loss in comprehensive Approaches
women using Depo-Provera contraceptive injection, all To adequately address reproductive health issues in patients should have adequate calcium and vitamin D adolescents and young adults, many factors must be taken intake."13 Future studies are required to identify the efficacy into consideration and a combination of approaches of supplementation as well as other CAM treatments in explored.64-71 Within the context of adolescent wellness, mitigating the side effects associated with DMPA, other lifestyle, together with the high rate of pregnancies and hormonal contraceptives, and the copper IUD.
newly acquired STIs, must be weighed against the short and long-term risks of hormonal interventions. Therefore, conclusion
it is imperative to find alternative options to DMPA while DMPA is used primarily as an effective contraceptive improving the proper and consistent use of condoms. for young adults who are considered to be less compliant.16 Furthermore, racial and socioeconomic disparities in pre- Although DMPA helps to address the high prevalence of scribing practices must be addressed by ensuring that all unintended teen and young adult pregnancies, the side young people have equal access to information. To accom- effects and long-term health risks are cause for concern. plish these goals, school-aged youth must be better edu- Given the possible impact of DMPA on future wellness, cated and the obstacles to compliance and healthy sexual- the fact that the vast majority of DMPA users are minority, ity addressed. Such an approach holds considerable prom- low-income women has raised ethical concerns. While ise given that a large number of educational programs cultural differences play a role in lifestyle and associated with common characteristics were demonstrated to be risk factors, reforming inequalities in sex education and effective in influencing the sexual health and contracep- reproductive health care may help to alleviate the serious tive practices of young people in various cultures and health issues relevant to all racial and socioeconomic Among several DMPA-induced adverse effects, con- Integrative Medicine's clinical recommendations
cerns exist about increased fracture risk over time. To date, Primary care clinicians can support well-informed studies have used BMD levels as the primary measure and choices by providing patients with a concise picture of the indication of fracture risk. Osteoporosis research, howev- risks and benefits of each contraceptive method. er, indicates that bone quality is equal y relevant.19,35 Additional y, by encouraging partners to attend these edu- Therefore, safety can only be definitively established based cational sessions, clinicians can facilitate responsibility on longitudinal studies of lifetime-fracture incidence in and healthy communication between both parties. In women with a history of DMPA use. compliant patients, the condom alone, or simultaneous Together with the potential influence of DMPA on use of the condom and diaphragm (without the irritant fracture risk, associated increases in the incidence of HIV spermicide), deserves consideration as a potential option. transmission warrant reevaluating the current practices All users need to be aware of the availability of the emer- for prescribing DMPA. The WHO failed to amend its pre- gency contraception pill should any issue arise. In non- scription guidelines based on their position that the hor- compliant patients, lower-risk contraceptive options war- monal link has not been proven; however, correlations rant consideration as a safer alternative to DMPA. between DMPA-induced immunophysiological changes Contraceptive prescribers may have a greater influ- and increased risk of HIV infection have been established. ence on reducing the incidence of STIs and unplanned These DMPA-induced changes are associated with suscep- pregnancies by distributing condoms and ensuring access tibility to HIV and other STIs. Additional y, DMPA may to education and/or links to videos with comprehensive accelerate HIV progression.
instructions (eg, www.sexualityandu.ca). Although intend- While it is essential to prevent unplanned pregnancies ed for postmenopausal women and older populations, a and their sequelae, these epidemiological links between modified FRAX assessment for younger populations might DMPA and HIV infections cannot be ignored. This need be a useful evaluation tool to more accurately assess frac- is underscored by the fact that DMPA is predominantly ture risk in current and potential DMPA/hormonal contra- prescribed to underserved populations who are living in ceptive users. Together with other variables that have an HIV-endemic areas. Moreover, the black box warning on impact on bone health, this score should reflect nutritional DMPA strongly advises that the contraceptive's use be status and take the prevalence of eating disorders and dis- limited to a period of 2 years. This warning suggests that ordered eating in younger populations into consideration.
DMPA is a short-term solution at best. Unfortunately, Integrative Medicine • Vol. 12, No. 1 • February 2013 This article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1543953X. To subscribe, visit imjournal.com
relying on DMPA as a means to address unplanned preg- 16. Westhoff C. Depot-medroxyprogesterone acetate injection (Depo-Provera): a highly effective contraceptive option with proven long-term safety. nancies in under-resourced areas, often results in pre- Contraception. 2003;68(2):75–87. scriptions that exceed the cautionary 2-year limit. 17. Depo Provera Fact Sheet: Committee on Women, Population, and the Environment. http://www.cwpe.org/node/185. Updated January 6, 2007. Given that disease prevention is influenced by health Accessed January 12, 2011.
during the formative years,70 it is crucial that health care 18. Baxter-Jones AD, Faulkner RA, Forwood MR, et al. Bone mineral accrual from 8 to 30 years of age: an estimation of peak bone mass. J Bone Miner Res. solutions weigh the long-term risks of hormonal interven- tions instituted at an early age. Some researchers suggest 19. International Osteoporosis Foundation. Facts and Statistics About replacing prescription recommendations for DMPA with Updated 2010. Accessed January 12, 2010.
lower-risk contraceptives, such as the IUD or sterilization. 20. Siris E and Delmas P. Assessment of 10-year absolute fracture risk: a new par- adigm with worldwide application. Osteoporos Int. 2008;19:383.
A clinician might also discuss the possibility of using the 21. Kanis J, Johnel O, Oden A, et al. FRAXtrade mark and the assessment of condom and diaphragm simultaneously. At a minimum, fracture probability in men and women from the UK. Osteoporos Int. condoms should be distributed, probiotics and estrogen/ 22. Fujiwara S, Nakamura T, Orimo H, et al. Development and application of a phytoestrogen creams concurrently prescribed, and bone Japanese model of the WHO fracture risk assessment tool (FRAXtrade mark). Osteoporos Int. 2008;19:429.
health actively addressed with all hormonal contracep- 23. Tosteson AN, Melton LJ, 3rd, Dawson-Hughes B, et al. Cost-effective osteo- tives. Furthermore, beyond unwanted pregnancies, true porosis treatment thresholds: the United States perspective. Osteoporos Int. prevention should address the high rate of newly acquired 24. Dawson-Hughes B, Tosteson A, Melton L, 3rd, et al. Implications of absolute STIs, the emotional aspects of sexuality, and obstacles to fracture risk assessment for osteoporosis practice guidelines in the USA. Osteoporos Int. 2008;19:449.
information and resources that support reproductive 25. Leslie W. Absolute fracture risk reporting in clinical practice: A physician- health in adolescents and young people of all demograph- centered survey. Osteoporos Int. 2008;19:459.
26. Langsetmo L, Morin S, Kovacs C, et al. Determining whether women with osteopenic bone mineral density have low, moderate, or high clinical fracture risk. Menopause. 2010;17(5):1010-6.
27. Unnanuntana A, Rebolledo B, Michael Khair M, Dicarlo E, Lane J. Diseases Affecting Bone Quality: Beyond Osteoporosis. Clin Orthop Relat Res. 2010 Nov 24. [Epub ahead of print].
28. Lopez L, Grimes D, Schulz K, Curtis K. Steroidal contraceptives: effect on The author wishes to thank Geno V. Romano, MD; David Lescheid, PhD, ND; Louis bone fractures in women. Cochrane Database Syst Rev. 2009 Apr Kuritzky, MD; and Michael Santiago, MD; for their helpful comments and feedback on a previous version of this article.
29. Berenson A, Rahman M, Radecki Breitkopf C, Bi LX. Effects of depot medroxyprogesterone acetate and 20 ug oral contraceptives on bone mineral density. Obstet Gynecol. 2008 October; 112(4): 788–799. 30. Agostino H, Di Meglio G. Low-dose oral contraceptives in adolescents: How references
low can you go? J Pediatr Adolesc Gynecol. 2010 Mar 11. 1. Abma J, Martinez G, Moser W, Dawson B. Teenagers in the United States: 31. Leary, WE. U.S. approves injectable drug as birth control. The New York sexual activity, contraceptive use, and childbearing, 2002. Vital Health Stat Times. October 30, 1992.
32. Kanis J. Diagnosis of osteoporosis and assessment of fracture risk. Lancet. 2. Hatcher R. Depo-Provera injections, implants, and progestin-only pills (minipills). In Hatcher RA, Trussell JS, Felicia H, et al. Contraceptive 33. Melton L, 3rd, Chrischilles E, Cooper C, et al. Perspective. How many women Technology. 18th rev. ed. New York, NY: Ardent Media; 2004:461–494.
have osteoporosis? J Bone Miner Res. 1992;7:1005.
3. Speroff L, Darney PD. Injectable contraception. A Clinical Guide for 34. Kanis JA, Johnell O, Oden A, et al. Long-term risk of osteoporotic fracture in Contraception. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; Malmo. Osteoporos Int. 2000;11:669.
35. Osteoporosis Promise and Progress: NIAMS. http://www.wrongdiagnosis.
4. Mosher WD, Martinez GM, Chandra A, Abma JC, Wil son SJ. Use of contra- ception and use of family planning services in the United States: 1982-2002. November 18, 2010. Accessed January 12, 2011.
Adv Data. 2004;(350):1-36.
36. Stini W, Osteoporosis in biocultural perspective. Annual Review of 5. Stacey D. Depo Provera: The birth control shot. http://contraception.about.
com/od/prescriptionoptions/a/depoprovera.htm. Updated August 26, 2010. 37. Kanis J, Delmas P, Burckhardt P, et al. Guidelines for diagnosis and manage- Accessed January 12, 2011.
ment of osteoporosis. The European Foundation for Osteoporosis and Bone 6. Trussell J. Contraceptive efficacy. In Hatcher RA, Trussell J, Nelson AL, Cates Disease. Osteoporos Int. 1997;7:390.
W, Stewart FH, Kowal D. Contraceptive Technology: Nineteenth Revised 38. Gullberg B, Johnell O, Kanis J. World-wide projections for hip fracture. Edition. New York NY: Ardent Media, 2007.
Osteoporos Int. 1997;7(5):407-13. 7. Pfizer. Depo-Provera Contraceptive Injection, US patient labeling. http:// 39. Morrison, Charles S., Hormonal contraception and HIV: an unanswered question. The Lancet Infectious Diseases. 2011;12(1):2-3.
Retrieved 2007-02-21. Accessed October 2004.
40. Bel uck, Pam. Contraceptive used in Africa may double the risk of H.I.V. The 8. Ojule J, Oriji V, Okongwu C. A five year review of the complications of pro- New York Times. 2011; Oct 3. http://www.nytimes.com/2011/10/04/ gestogen only injectable contraceptive at the University of Port-Harcourt Teaching Hospital. Niger J Med. 2010;19(1):87-95.
41. Hel Z, Stringer E, Mestecky J. Review: Sex steroid hormones, hormonal con- 9. Meier C, Brauchli Y, Jick S, Kraenzlin M, Meier CR. Use of depot medroxy- traception, and the immunobiology of human immunodeficiency virus-1 progesterone acetate and fracture risk. J Clin Endocrinol Metab. infection. Endocrine Reviews. February 1, 2010;31(1):79-97.
2010;95(11):4909-16. Epub 2010 Aug 4.
42. AHN. Who clarifies guidance on hormonal contraception and HIV. Gant 10. Albertazzi P, Bottazzi M, Steel S. Bone mineral density and depot medroxy- Daily. February 17, 2012. http://gantdaily.com/2012/02/17/who-clarifies- progesterone acetate. Contraception. 2006;73(6):577-83. 11. Walsh JS, Eastell R, Peel NF. Effects of Depot medroxyprogesterone acetate 43. Miller L, Patton DL, Meier A, Thwin SS, Hooton TM, Eschenbach DA. on bone density and bone metabolism before and after peak bone mass: a Depomedroxyprogesterone-induced hypoestrogenism and changes in vaginal case-control study. J Clin Endocrinol Metab. 2008;93(4):1317-23.
flora and epithelium. Obstet Gynecol. 2000 Sep;96(3):431-9.
12. Tolaymat L, Kaunitz A. Use of hormonal contraception in adolescents: skele- 44. Walter J, Fraga L, Orin MJ, Decker WD, Gipps T, Stek A, Aldrovandi GM. tal health issues. Curr Opin Obstet Gynecol. 2009;21(5):396-401.
Immunomodulatory factors in cervicovaginal secretions from pregnant and 13. FDA Black Box Warning: Physician Information http://www.accessdata.fda.
non-pregnant women: a cross-sectional study. BMC Infect Dis. 2011 Sep 14. Scholes D, LaCroix A, Ichikawa L, Barlow W, Ott S. Injectable hormone con- 45. Beagley KW, Gockel CM. Regulation of innate and adaptive immunity by the traception and bone density: results from a prospective study. Epidemiology. female sex hormones oestradiol and progesterone. FEMS Immunol Med 2002;13(5):581-7. Erratum in: Epidemiology. 2002;13(6):749.
Microbiol. 2003 Aug 18;38(1):13-22. 15. Kaunitz A, Arias R, McClung M. Bone density recovery after depot medroxy- 46. Wira CR, Fahey JV. The innate immune system: gatekeeper to the female progesterone acetate injectable contraception use. Contraception. reproductive tract. Immunology. 2004 Jan;111(1):13-5. 2008;77(2):67-76. Integrative Medicine • Vol. 12, No. 1 • February 2013 This article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1543953X. To subscribe, visit imjournal.com
47. Brabin L. Interactions of the female hormonal environment, susceptibility to 75. Galbreath CW, Scholliegerdes EJ, Lardy GP, Odde KG, Wilson ME, Shroeder viral infections, and disease progression. AIDS Patient Care STDS. 2002 JW, Vonnahme KA. Effect of feeding flax or linseed meal on progesterone clearance rate in ovariectomized ewes. Domest Anim Endocrinol. 2008 48. Kaushic C, Zhou F, Murdin AD, Wira CR. Effects of estradiol and progester- Aug:35(2):164-9. Epub 2008 Jun 5. one on susceptibility and early immune responses to Chlamydia trachomatis 76. Simons R, Gruppen H, Bovee TF, Verbruggen MA, Vincken JP. Prenylated infection in the female reproductive tract. Infect Immun. 2000 Jul;68(7):4207- isoflavonoids from plants as selective estrogen receptor modulators (phytoS- ERMS). Food Funct. 2012 Aug:3(8)810-27. Epub 2012 Jun 11. 49. Hladik F, McElrath MJ. Setting the stage: host invasion by HIV. Nat Rev 77. Tiyasatkulkovit W, Charoenphandhu N, Wongdee K, Thongbunchoo J, Krishnamra N, malaivijitnond S. Upregulation of osteoblastic differentiation 50. Martin HL, Richardson BA, Nyange PM, Lavreys L, Hillier SL, Chohan B, marker mRNA expression in osteoblast-like UMR106 cells by puerarin and Mandaliya K, Ndinya-Achola JO, Bwayo J, Kreiss J. Vaginal lactobacilli, phytoestrogens from Pueraria mirifica. Phytomedicine. 2012 Oct microbial flora, and risk of human immunodeficiency virus type 1 and sexu- 15;19(13):1147-55. Epub 2012 Aug 27. al y transmitted disease acquisition. J Infect Dis. 1999;180:1863–1868.
78. Sung MJ, Davaatseren M, Hur HJ, Kim HJ, Ryu SY, Choi YH, Cha MR, Kwon 51. Ghanem KG, Shah N, Klein RS, Mayer KH, Sobel JD, Warren DL, Jamieson DY. Antiosteoporotic activity of Saururus chinensis extract in ovariectomized DJ, Duerr AC, Rompalo AM. Influence of sex hormones, HIV status, and rats. Phytother Res. 2012 Aug; 26(8):1182-8. Epub 2012 Jan 4. concomitant sexually transmitted infection on cervicovaginal inflammation. 79. Casado-Diaz A, Santiago-Mora R, Dorado G, Quesada-Gomez JM. The J Infect Dis. 2005;191:358–366. omega-6 arachidonic fatty acid, but not the omega-3 fatty acids, inhibits 52. Li A, Felix JC, Yang W, Jain JK. Effect of mifepristone on the expression of osteoblastogenesis and induces adipogenesis of human mesenchymal stem endometrial secretory leukocyte protease inhibitor in new medroxyproges- cells: potential implication in osteoporosis. Osteoporos Int. 2012 Oct 27. terone acetate users. Fertil Steril. 2008 Sep;90(3):872-5. Epub 2007 Dec 26.
[Epub ahead of print]. 53. Hladik F, Sakchalathorn P, Bal weber L, Lentz G, Fialkow M, Eschenbach D, 80. Tartibian B, Hajizadeh Maleki B, Kanaley J, Sadeghi K. Long-term aerobic McElrath MJ. Initial events in establishing vaginal entry and infection by exercise and omega-3 supplementation modulate osteoporosis through human immunodeficiency virus type-1. Immunity. 2007;26:257–270.
inflammatory mechanisms in post-menopausal women: a randomized, 54. Wieser F, Hosmann J, Tschugguel W, Czerwenka K, Sedivy R, Huber JC. repeated measures study. Nutr Metab (Lond). 2011 Oct 15;8:71. Progesterone increases the number of Langerhans cel s in human vaginal epi- 81. Moon HJ, Kim TH, Byun DW, Park Y. Positive correlation between erythro- thelium. Fertil Steril. 2001;75:1234–1235.
cyte levels of n-3 polyunsaturated fatty acids and bone mass in postmeno- 55. Jain AK. Hormonal contraception and HIV acquisition risk: implications for pausal Korean women with osteoporosis. Ann Nutr Metab. 2012;60(2):146-53. individual users and public policies. Contraception. 2012 Apr 26. [Epub ahead Epub 2012 Apr 14. 56. Roberts D. Killing the Black Body: Race, Reproduction, and the Meaning of Liberty. New York, NY: Random House, Inc; 1997.
57. Heavner, J. Broken treaties, empty promises: An introduction to Native American women's reproductive health issues. http://www.whale.to/b/ heavner.html. Accessed January 12, 2011.
58. Duggan G. Vice-President of Women for Women's Health. Statement Depo- provera and women's health. Vancouver Sun, February 1993.
59. Center for Disease Control and Prevention. http://www.cdc.gov/nchs/nsfg/ abc_list_i.htm. National Survey of Family Growth. 2006-2008.
60. McGough P, Bigrigg A. Effect of depot medroxyprogesterone acetate on bone density in a Scottish industrial city. Eur J Contracept Reprod Health Care. 2007;12(3):253-9. 61. WHO clarifies guidance on hormonal contraception and HIV. February 17, Gag-Order-on-Reproductive-Health.aspx. February 13, 2012.
63. Sorojini, NB. Why women's groups oppose injectable contraceptives. Indian J Med Ethics. January-March 2005.
64. DiClemente RJ, Wingood GM, Rose ES, et al. Efficacy of Sexually Transmitted Disease/Human Immunodeficiency Virus Sexual Risk- Reduction Intervention for African American Adolescent Females Seeking Sexual Health Services A Randomized Control Trial. Arch Pediatr Adolesc 65. DiClemente RJ, Crosby RA, Kegler MC. Emerging Theories in Health Promotion Practice and Research, San Francisco, CA: John Wiley & Sons, Inc; 66. Kirby DB, Baumler E, Coyle KK, et al. The "Safer Choices" intervention: its impact on the sexual behaviors of different subgroups of high school stu- dents. J Adolesc Health. 2004;35(6):442-52.
67. Koyama A, Corliss HL, Santelli JS. Global lessons on healthy adolescent sexu- al development. Curr Opin Pediatr. 2009;21(4):444-9.
68. Family connectedness and sexual risk-taking among urban youth attending alternative high schools. Perspect Sex Reprod Health. 2003;35(4):174-9.
69. Frost JJ, Forrest JD. Understanding the impact of effective teenage pregnancy prevention programs. Fam Plann Perspect. 1995;27(5):188-95.
70. Eaton D, Kann L, Kinchen S, et al. CDC Youth Risk Behavior Surveil ance - United States, 2005. Atlanta, GA; 2006 Morbidity and Mortality Weekly Report, Vol. 55, No. SS-5. http://www.cdc.gov/mmwr/pdf/ss/ss5505.pdf. Accessed January 12, 2011.
71. Kirby DB. The Impact of Sex Education on the Sexual Behaviour of Young People. United Nations: Department of Economic and Social Affairs: Population Division, Exprt Paper No. 2011/12. New York. 2011.
72. Li J, McCormick J, Bocking A, Reid G. Importance of vaginal microbes in reproductive health. Reprod Sci. 2012 Mar;19(3):235-42.
73. Morali G, Polatti F, Metelitsa EN, Mascarucci P, Magnani P, Marrè GB. Open, non-controlled clinical studies to assess the efficacy and safety of a medical device in form of gel topical y and intravaginal y used in postmenopausal women with genital atrophy. Arzneimittelforschung. 2006;56(3):230-8. 74. Vitale DC, Piazza C, Melilli B, Drago F, Salomone S. Isoflavones: estrogenic activity, biological effect and bioavailability. Eur J Drug Metab Pharmacokinet. November 17, 2012 [Epub ahead of print]. Integrative Medicine • Vol. 12, No. 1 • February 2013
Download the original attachment Criminal Charges concerning Bioterrorism Acts and Mass Submitted: FBI OFFICER EMBASSY OF THE UNITED STATES Boltzmanngasse 16 A-1090 Vienna Date: June 10, 2009 I. Introduction: Summary of Claims II. Factual Background III. Evidence the "swine flu" vaccines are bioweapons IV. Scientific evidence the "swine flu" virus is an