In collaboration with the American College of Veterinary Surgeons
Treating Navicular Syndrome in Equine Patients*
R. Wayne Waguespack, DVM, MS, DACVS
R. Reid Hanson, DVM, DACVS, DACVECC
Auburn University Abstract: Navicular syndrome is a chronic, progressive condition affecting the navicular bone and bursa, deep digital flexor tendon
(DDFT), and associated soft tissue structures composing the navicular apparatus. The treatment options for navicular syndrome are
as varied as the proposed causes of the condition. The severity of clinical signs, intended use and workload of the horse, and owner compliance with therapy are important considerations in developing a treatment plan. Nonsurgical treatment of navicular syndrome consists of rest, hoof balance and corrective trimming/shoeing, and medical therapy, including administration of systemic antiinflam-matories, hemorheologic medications, and intraarticular medications. While surgical therapy can include desmotomy of the col ateral (suspensory) ligaments of the navicular bone, palmar digital neurectomy is more commonly performed when medical therapy is inef- fective. Recently, adjunct therapies, such as acupuncture and extracorporeal shock wave therapy, have also been used to treat horses with navicular syndrome. Because of the wide range of pathologic changes and the lack of a definitive cure associated with navicular syndrome, treatment is directed toward the individual horse, focusing on the management of clinical signs to al eviate stress and retard degenerative changes of the navicular bursal and navicular regions. Navicular syndrome is a chronic progressive condi- the surrounding soft tissues have been reported, primarily tion affecting the navicular bone and bursa as well involving the palmar fibrocartilage of the navicular bone,
as the associated soft tissue structures1 (FIGURE 1). its underlying subchondral and trabecular bone, and the
This article discusses treatment options and future research apposing DDFT. In addition, erosions and fibrillation of the involving navicular syndrome.
fibrocartilage, remodeling of the underlying subchondral The treatment options for navicular syndrome are as var- and trabecular bone, palmar cortical bone erosion, DDFT ied as the proposed causes of the condition. As new ideas fibrillation, core lesions, and adhesions have been recog-regarding the etiology have been proposed, new treatment nized.3–5 These changes are remarkably similar to those seen regimens have followed. Recently, with the use of computed in osteoarthritis; however, in navicular syndrome, the pal- tomography (CT) and magnetic resonance imaging (MRI), mar fibrocartilage of the navicular bone and the apposing it appears that the deep digital flexor tendon (DDFT) at DDFT are involved instead of two apposing hyaline carti- the level of the navicular bone may play a more significant lage surfaces.
role than previously understood1,2 (FIGURE 2). Despite new Knowledge of these changes may eventually help clarify
information regarding navicular syndrome, many treatments why some treatment regimens produce clinical improve-remain based on modification of pain rather than elimina- ment and allow development of more specific therapeutic tion or reduction of pathologic processes. In patients with alternatives. In lieu of this, treatment options are focused navicular syndrome, changes in the navicular bone and on management of clinical signs and should be designed to alleviate stress on the navicular region and prevent or retard *A companion article, "Navicular Syndrome in Equine Patients: degenerative changes within the navicular bone and bursal Anatomy, Causes, and Diagnosis," appeared in the December 2010 Vetlearn.com January 2011 Compendium: Continuing Education for Veterinarians® E1
Copyright 2011 MediMedia Animal Health. This document is for internal purposes only. Reprinting or posting on an external website without written permission from MMAH is a violation of copyright laws.
The severity of clinical signs, the horse's intended use and workload, and the owner's compliance with therapy are important considerations in developing a treatment plan. Young horses and horses with less severe clinical signs are often candidates for conservative therapy. Nonsurgical treatment of navicular syndrome consists of rest, hoof bal-ance and corrective trimming/shoeing, and medical therapy, including systemic antiinflammatories, hemorheologic med-ications, and intraarticular medications.6–8 RestOne of the most overlooked components of treatment is rest. Continued stress on the navicular region leads to structural failure and eventual breakdown. Time is necessary to allow soft tissue inflammation to subside and bone remodeling to take place. The time necessary to reduce inflammation var-ies on an individual basis. Absolute confinement is contrain-dicated; pasture or paddock turnout is sufficient. Corrective Shoeing and Hoof Balance Careful evaluation of foot conformation and balance is the focal point in nonsurgical treatment of navicular syndrome. Many horses respond to correction of hoof abnormalities.9 The goal is to reduce forces on the navicular region by (1) cor- recting hoof balance and the hoof–pastern axis, (2) allowing the use of all weightbearing structures of the hoof by main-taining the heel mass and protecting the palmar aspect of The navicular bursa (black arrow), distal interphalangeal
the foot from concussion, and (3) decreasing the work of the joint (blue arrow), deep digital flexor tendon, impar liga-
moving foot by either shortening the toe length of the foot to ment, and collateral sesmoidean ligament. (NB = navicular
permit an easier breakover or rolling the toe of the shoe.
bone; PII = second phalanx; PIII = third phalanx)
Horses with navicular syndrome often have unbalanced hooves consisting of long toes with low, underrun, and
contracted heels (FIGURE 3). One of the first requirements
of hoof balance is hoof–pastern alignment. Proper hoof–
pastern alignment is assumed if a straight line can be drawn
through the dorsal pastern and dorsal hoof wall (FIGURE
3). The foot should be trimmed to maintain heel mass and
shorten the toe to facilitate breakover if the hooves are char-
acterized by long toes. Use of the so-called four-point or
natural-balance trim has recently been favored by some clinicians, but the same principles of breakover can prob- ably be achieved with more traditional trimming if the toe is shortened sufficiently. Radical changes in foot trimming Surgical Views is a col aborative series between the American may temporarily increase lameness; therefore, correct foot Col ege of Veterinary Surgeons (ACVS) and Compendium. balance may need to be achieved in stages.
All Surgical Views articles are peer-reviewed by ACVS In principle, a hoof with proper hoof–pastern alignment has the appropriate amount of tension or force exerted on the navicular bone by the DDFT. In horses with low heels, To locate a diplomate, ACVS has an online directory that includes practice
setting, species emphasis, and research interests (acvs.org/Veterinary
correct alignment can be established with selective trimming or, more commonly, by elevating the heels with a wedge-heel E2 Compendium: Continuing Education for Veterinarians® January 2011 Vetlearn.com
Advanced imaging modalities such as MRI and CT have helped veterinarians
realize that navicular syndrome involves more than just the navicular bone in horses.
(A) MRI of the navicular region. Cross-sectional and longitudinal
views are shown. (B) CT scan of the navicular region. Based on
the visible asymmetry, an erosive lesion is noted in the navicu-
balance. This is determined either by obtaining a dorsopal-mar radiograph of the foot or watching the horse walk to ensure that the medial and lateral aspects of the hoof hit the ground simultaneously. If the hoof cannot be trimmed to establish normal hoof–pastern alignment or lateromedial balance, shoes can be applied to encourage the hoof to grow correctly. Many types of shoes have been recommended for horses with navicular syndrome. Full-bar, egg-bar, natural balance, and wide-web aluminum or steel shoes with or without elevated heels have been used to support the heels and move the weightbearing axis in a palmar direction in
horses with low, collapsed, and underrun heels (FIGURE 4).
A recent study showed that using egg-bar shoes with no heel elevation in clinically normal Dutch Warmblood horses shoe.9 In a study of normal Dutch Warmblood horses, heel with well-conformed feet did not reduce the force on the elevation with a 6° wedge reduced the maximal force on the navicular bone compared with using regular flat shoes.10 navicular bone by 24% compared with use of flat shoes.10 In However, these findings cannot necessarily be translated to another study, force-plate analysis indicated that lameness sig- lame horses with less-than-ideal foot conformation. In the nificantly decreased in horses with navicular syndrome that same study, heel wedges did reduce the force on the navic- were shod to produce a 3° heel elevation alone or in com- ular bone compared with flat shoes.10 In a study evaluat- bination with phenylbutazone administration.11 Lateromedial ing 55 horses with clinically diagnosed navicular syndrome, radiographs may be necessary to demonstrate whether a 53% had permanent relief of lameness 12 to 40 months after horse needs more or less heel elevation. If the horse's lame- application of egg-bar shoes.12 In another study, horses shod ness worsens after elevation of the toe using the wedge test, with egg-bar shoes showed histomorphometric evidence of some degree of heel elevation may be beneficial.
altered navicular bone modeling compared with untreated The hoof should also be maintained in medial-to-lateral controls.13 In any case, shoes should be set (1) beyond the Vetlearn.com January 2011 Compendium: Continuing Education for Veterinarians® E3
Unbalanced hooves and proper hoof–pastern alignment.
(A) Unbalanced hooves (long toes and low, underrun heels) of a horse with navicular syndrome. Note the medial-to-lateral imbal-
ance in the horse's feet. One of the first requirements for hoof balance is hoof–pastern alignment. (B) Proper hoof–pastern align-
ment is assumed if a straight line can be drawn through the bony column of the phalanges. The dorsal hoof wall should be parallel
to the dorsal aspect of the pastern. A line bisecting the third metacarpal bone should reach the ground at the weightbearing part of
heels to provide heel support and (2) full or wide to allow nolone acetonide, betamethasone sodium phosphate) have proper hoof expansion.7,10 been injected into the navicular bursa and the distal inter- phalangeal joint (DIPJ) to treat navicular syndrome, and the results have varied.7,14 These powerful antiinflammatories Anti nflammatories are routinely used in combination with sodium hyaluronate to control clinical signs associated with navicular syndrome. Corticosteroids (e.g., methylprednisolone acetate, triamci- Most clinicians medicate the DIPJ when treating navicular syn- E4 Compendium: Continuing Education for Veterinarians® January 2011 Vetlearn.com
drome.15 Medications injected into the DIPJ, which is near the navicular bursa, have been shown to diffuse to the navicular region. A study by Pauwels et al15 showed that clinically effective concentrations of methylprednisolone and triamcinolone diffused between the DIPJ and the navicular bursa. This is also supported by the response to treatment of clinical cases of navicular syndrome. Over time, some horses stop responding to intraarticular therapy of the DIPJ. Intrabursal therapy may provide another option for reducing inflammation in the navicular region of the foot. One study showed that 80% of horses that no longer responded to traditional therapy for navicular syndrome (i.e., corrective shoeing, administration of systemic antiinflam-matories, intraarticular therapy of the DIPJ) were sound 2 weeks after intrabursal injections of corticoster-oids, sodium hyaluronate, and amika-cin.16 The mean duration of soundness Full-bar, egg-bar, and wide-web aluminum or steel shoes have been used to
support the heels and move the weightbearing axis in a palmar direction in horses with
in this study was 4.5 months.
low, collapsed, and underrun heels.
In recent years, interleukin-1 recep- tor antagonist protein (IRAP) therapy (Vet Arthrex Biosystems, Bonita Springs, FL) has been used ical situations. NSAID toxicosis may develop with long-term increasingly in veterinary practices to treat osteoarthri- use of certain NSAIDs because of the nonselective inhibi- tis in horses. Several studies have investigated the effects tion of cyclooxygenases 1 and 2. In a study comparing oral of IRAP therapy for this purpose.17–19 While the efficacy of firocoxib (a highly selective cyclooxygenase-2 inhibitor) IRAP therapy for treating navicular syndrome has not been and oral phenylbutazone in controlling pain associated with investigated, some clinicians have noted positive effects naturally occurring osteoarthritis, there was no statistically from IRAP injections either in the DIPJ or directly in the significant difference.24navicular bursa. IRAP is a naturally occurring protein that Other drugs with potential antiinflammatory proper-works by occupying receptor sites on the membrane of car- ties that may be useful for treating navicular syndrome are tilage cells, preventing the normal cytokine-initiated inflam- glucosamine–chondroitin sulfate compounds, polysulfated matory cascade.19,20 Blockage of matrix metalloproteinases glycosaminoglycans (PSGAGs), and sodium hyaluronate.16,25 and cytokines (e.g., interleukin-1) reduces their degenerative Glucosamine–chondroitin sulfate compounds are given effects on cartilage, preventing degenerative joint disease orally, sodium hyaluronate can be given intravenously or and osteoarthritis.18,19,21–23 intrasynovially, and PSGAGs can be given intrasynovially or intramuscularly. Administration of glucosamine–chondroitin sulfate compounds and intramuscular PSGAGs has been NSAIDs have been the mainstay of navicular syndrome shown to reduce clinical signs associated with navicular therapy for many years.7,8,11 The analgesic and antiinflamma- syndrome.25–27 These medications are effective only while tory properties of NSAIDs make them attractive therapeutic they are administered. Lameness reappears after the therapy agents. Phenylbutazone is the most commonly used NSAID. is discontinued. The bioavailability of glucosamine–chon- Flunixin meglumine, diclofenac, carprofen, naproxen, keto- droitin sulfate compounds in horses had been questioned, profen, meclofenamic acid, and aspirin are also used in clin- but it has now been documented.28 Vetlearn.com January 2011 Compendium: Continuing Education for Veterinarians® E5
in treating navicular syndrome, the Anatomy surrounding the palmar digital nerve.
lameness scores of horses receiv-ing propentofylline significantly im- proved.35 In a study evaluating the oral administration of pentoxifylline, therapeutic levels were achieved in horses.36 This was not supported in an earlier study in which oral admin- istration of pentoxifylline had no significant effects on digital blood flow to the equine foot.30 The find-ings in these two studies may be due to the use of different dosages of Bone Metabolism Medications (A) The lateral aspect of the phalangeal
Bisphosphonates, such as tiludronate, region of the distal limb. The needle is in the
are used to normalize bone metab- ligament of the ergot, which can be incor-
rectly identified as the palmar digital nerve
olism through inhibition of bone during neurectomy. (B) The needle is in the
resorption; however, bisphospho- palmar digital nerve adjacent to the palmar
nates approved for horses are not digital artery, which is elevated by the surgi-
available in the United States. Areas cal instrument. The ligament of the ergot is
of increased bone resorption and just dorsal to the palmar digital artery and
formation are common on radio- graphs of horses with navicular syn-drome. Delguste et al37 showed that tiludronate reduces bone resorption Isoxsuprine hydrochloride (a β agonist) is a peripheral and prevents long-term osteopenia in healthy horses. Several vasodilator that has been successfully used in relieving studies have evaluated the dosages (0.1 mg/kg q24h IV for 10 the clinical signs of navicular syndrome.29,30 The drug can days versus 1 mg/kg IV in a single dose), bioavailability, and also decrease blood viscosity and platelet aggregation.31 pharmacologic effects of tiludronate in horses.38,39 In a clini- Isoxsuprine is given orally, and numerous dosages have cal trial by Denoix et al,38 horses treated with tiludronate (1 been recommended. The specific mode of action of isoxsu- mg/kg IV in a single dose) showed significant improvement
prine in treating navicular syndrome is unknown. In a study in lameness and returned to their normal level of activity
by Ingle-Fehr and Baxter,30 oral isoxsuprine did not increase within 2 to 6 months after treatment.
blood flow to the equine foot. Isoxsuprine also binds strongly
to α adrenoreceptors and, therefore, may be active despite Surgical Therapy
insignificant but measurable levels in plasma.32,33 The drug Palmar Digital Neurectomy
may also have antiinflammatory and hemorheologic prop- Palmar digital neurectomy (PDN) involves disrupting the
erties, which may be the source of its beneficial effects in nerve supply to the palmar one-third of the hoof to alleviate
horses with navicular syndrome. A clinical trial that evalu- heel pain (FIGURES 5 and 6). PDN is considered a palliative
ated the clinical efficacy of isoxsuprine for treating navicular procedure because it only alleviates the pain associated with
syndrome in horses demonstrated a decrease in lameness.29 navicular syndrome and does not prevent or retard progres-
The length of the treatment period varies, with some horses sion of the damaging processes. The various PDN meth- showing clinical improvement for months after discontinu- ods share the common goal of atraumatically sectioning the ing therapy. One author noted that some horses that did not nerve to minimize the likelihood of the most common com-respond to an isoxsuprine dosage of 0.6 mg/kg PO q12h did plication: neuroma formation.40–45 Research suggests that the respond satisfactorily to 0.9 mg/kg PO q12h.34 simple guillotine technique results in the longest period Pentoxifylline and propentofylline are other hemo- of desensitization and least chance of neuroma formation rheologic agents that have been used for treating navicular compared with epineural capping and carbon dioxide laser syndrome. In one study on the efficacy of propentofylline division.40,43,44 The guillotine technique can be performed in E6 Compendium: Continuing Education for Veterinarians® January 2011 Vetlearn.com
several different ways. Some clinicians make a 1- to 2-cm incision over the nerves for each affected foot, just proxi-mal to the collateral cartilages, and remove approximately 1 cm of palmar digital nerve.41 Other clinicians make either a 3- to 4-cm incision per nerve or two 1-cm incisions (one
just proximal to the collateral cartilage, and the other just
distal to the proximal sesamoid bones)34,42,45 (FIGURE 6). In
this method, approximately 3 to 4 cm of each palmar digital
nerve is removed.42,45
Postoperative care is extremely important in the success of this procedure. Horses are confined to a stall and hand-walked for 1 month. Support bandages are maintained while the horse is on stall rest. Some clinicians support postopera-tive perineural injection of the proximal transected nerve root with a corticosteroid to reduce postoperative inflam-mation. Limited exercise, bandaging, and an atraumatic sur- gical procedure all have a significant effect on preventing neuroma formation. Clinical interpretation of the long-term resolution of lame- ness after PDN varies, as do reported success rates. Published reports indicate that up to 92% of horses were in work 1 year after PDN.43 In the same study, 77% of horses in work 1 year after surgery were sound.43 In another study, 74% of horses were sound 1 year after PDN; however, this percentage decreased to 63% after 2 years.41 Complications associated with PDN include failure to alleviate lameness due to remain-ing accessory branches of the palmar digital nerve, rupture of the DDFT, subluxation or luxation of the DIPJ, and deep hoof infection; therefore, PDN should not be recommended casually. Recurrence of lameness is most commonly associ-ated with reinnervation or neuroma formation. Development of a painful neuroma may be managed with surgical excision or perineural injections of Sarapin (High Chemical Company, Levittown, PA) and triamcinolone acetate. Alternative Surgical Options Navicular bursoscopy is usually a diagnostic tool but may be used for treatment, depending on the pathology noted on endoscopic examination.46,47 Desmotomy of the collateral (suspensory) ligaments of the navicular bone has been recommended as a surgical treatment for navicular syndrome.48 In a study evaluating Palmar digital neurectomy using Black's technique,
in which the guillotine technique is used for the proximal and
118 horses, 76% of treated horses were sound 6 months after distal incisions to remove 3 to 4 cm of the palmar digital nerve.
surgery, but only 43% remained sound after 3 years.49 In a study from New Zealand, 12 of 17 horses were sound at least 6 months after surgery.50 clinical trials have been performed to date, but anecdotal Surgical drilling of cyst-like lesions involving the navicu- evidence suggests that this may be a treatment option in lar bone via an arthroscopic approach has been described, horses with severe bone edema identified on MRI. but no follow-up data are available at this time.51 Desmotomy of the accessory ligament of the DDFT has Some clinicians advocate core decompression of the been described as a treatment for navicular syndrome in navicular bone in horses with navicular syndrome.52 No horses with a markedly upright foot conformation.53 Vetlearn.com January 2011 Compendium: Continuing Education for Veterinarians® E7
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43. Matthews S, Dart AJ, Dowling BA. Palmar digital neurectomy in 24 horses using
effects of extracorporeal shock wave therapy for treatment of navicular disease in the guillotine technique. Aust Vet J 2003;81:402-405.
horses. Vet Surg 2005;34:554-558.
44. Evans LH. Procedures used to prevent painful neuromas. Proc AAEP 1970:103.
58. Blum N, Kreling K, Litzke LF. The use of extracorporeal shock wave therapy in
45. Black JB. Palmar digital neurectomy: an alternative surgical approach. Proc AAEP
horses with navicular disease. Pferdheilkunde 2005;21:29-38.
Vetlearn.com January 2011 Compendium: Continuing Education for Veterinarians® E9
CE TEST This article qualifies for 3 contact hours of continuing education credit from the Auburn University College of Veterinary
Medicine. Subscribers must take individual CE tests online and get real-time scores at Vetlearn.com. Those who wish to apply this credit
to fulfil state relicensure requirements should consult their respective state authorities regarding the applicability of this program. 1. Which change(s) has/have been associ-
b. In one study, 80% of horses that no
a. isoxsuprine hydrochloride
ated with the navicular bone and sur-
longer responded to traditional therapy rounding soft tissue structures in horses
for navicular syndrome were sound 2 with navicular syndrome?
weeks after intrabursal injections of a. erosions and fibril ation of the
corticosteroids, sodium hyaluronate, and amikacin.
8. Regarding PDN, which surgical
b. remodeling of the underlying subchon-
c. Administration of glucosamine–
technique(s) best minimizes the poten-
dral and trabecular bone chondroitin sulfate compounds and tial for neuroma formation?
c. palmar cortical bone erosion
intramuscular PSGAGs is reported to a. the guillotine technique
d. all of the above
alter the clinical signs associated with b. epineural capping
c. carbon dioxide laser division
2. Which medical treatment(s) is/are used
in horses with navicular syndrome?
a. systemic anti nflammatories
5. Which medication(s) can be injected
9. Which potential complication(s) is/are
b. corrective shoeing
into the DIPJ or navicular bursa to con-
associated with PDN?
c. systemic hemorheologic medications
trol clinical signs in horses with navicu-
a. failure to al eviate lameness due to
d. all of the above
remaining accessory branches of the palmar digital nerve 3. The goal of shoeing a horse with navicu-
b. rupture of the DDFT
lar syndrome is to reduce forces on the
c. sodium hyaluronate
c. fracture of the third phalanx
navicular region by
a. establishing the correct hoof balance
and hoof–pastern axis.
6. Which medication(s) can be adminis-
10. Which product(s) can be used in chemi-
b. permitting an easier breakover of the
tered to minimize pain and inflammation
cal ablation of sensory fibers in the
associated with navicular syndrome?
palmar digital nerves?
c. moving the weightbearing surface of
the hoof forward away from the heel.
b. flunixin meglumine
b. liquid nitrogen
c. cobra venom
d. all of the above
d. all of the above
4. Which statement(s) regarding treatment
of navicular syndrome is/are true?
7. Which medication(s) has/have been
a. Injecting steroids into the DIPJ does
shown to decrease the clinical signs
not treat the navicular region of the associated with navicular syndrome
(clinically or in studies)?
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Coalition on Abortion / Breast Cancer Post Office Box 957133 Hoffman Estates, IL 60195-3051 U.S.A. Toll Free: 877.803.0102 Local: 847.421.4000 [email protected] Dear Friend: There is, most definitely, a war being waged against women. But, it's not what Planned Parenthood and other radical organizations on the left would have you believe. They expect you believe the nonsensical claim that Re-publicans are waging a war on women if they dare oppose Planned Parenthood's anti-women agenda which will use ObamaCare as its vehicle to expand sexual license in the U.S., augment population control efforts, and open Planned Parenthood's coffers to receive a flood of taxpayer funds. In its implementation of ObamaCare, the U.S. Department of Health and Human Services has mandated that employers must purchase health insurance that would provide employees with free sterilizations and (cancer-causing) hormonal contraceptive steroids and abortifacients. That would include the birth control pill (oral contraceptives) and the injection, Depo Provera birth control. And the U.S. Supreme Court has agreed for the first time that forcing citizens to buy a product they don't want - in this case, health insurance - is a tax that the federal government may impose. More American women will die of cancer because of the ObamaCare mandate. Women and their unborn chil-dren will be sacrificed on Planned Parenthood's altar of greed! Like every other Big Lie that has been told throughout history when infamous political leaders and others have used propaganda to conceal their nefarious purposes, Planned Parenthood and its political allies have repeated their canned slogan, "Stop the war on women," ad nauseum in the hope it will ultimately stick. They would have you believe that women around the world are dying in the streets for lack of hormonal contraceptive steroids and induced abortions. They make it sound as if taking hormonal steroids and having abortions are as necessary to women's health as drinking water and breathing air! That's their idea of "reproductive health"! But here's the truth! As the promoters and sellers of the birth control pill and the injection, Depo Provera birth control, Planned Parenthood and its allies are clearly the ones waging a war on women! Five studies have strongly linked use of Depo Provera with a 1.5- to 2.3-fold increased breast cancer risk. (Other grave risks include increased susceptibility to HIV/AIDS and bone mineral density loss.) Christopher Li, Janet Daling and other researchers from the Fred Hutchinson Cancer Research Center in Seattle conducted the first "large scale U.S. study" on the link between use of Depo Provera and in-creased breast can-cer risk. They found a statistically significant 2.2-fold elevated risk of invasive breast cancer among women who had used Depo Provera recently for at least 12 months. Significantly, the authors noted that the 2003 Women's Health Initiative study demonstrated a 1.24-fold ele-vated risk among those who used estrogen plus progestin hormone replacement therapy (HRT). On the other hand, estrogen only HRT "had a nonstatistically significant reduced risk." Depo Provera contains only progestin. So why does it raise risk?