Depo-Medroxyprogesterone
Acetate Clinical Update
Scott J Spear, MD
Medical Director
Planned Parenthood of the Texas Capital Region &
Planned Parenthood of Central Texas
Clinical Assistant Professor of Obstetrics & Gynecology
UT Southwestern Medical Center
Learning Objectives
• Provide background and description of DMPA
• List mechanism of action, efficacy,
advantages, and disadvantages of DMPA
• Describe examples of good candidates for
DMPA use
• Discuss DPMA Black Box Warning
• Discuss research on DMPA and it’s impact on
BMD and skeletal health
more…
Learning Objectives (continued)
• Critically examine recommendation for “addback” estrogen or DEXA scans for minors
• Present ACOG’s and WHO’s Guidance on
DMPA
DMPA: Background
• Since introduction in
1963, used safely in >30
million women worldwide
• >2 million US women
currently use DMPA
• Temporary bone loss
ACOG Committee Opinion No. 415. Obstet Gynecol. 2008.
Description of DMPA
• Depot Medroxyprogesterone
Acetate (DMPA)
• Brand names: DepoProvera® and Depo-subQ
provera 104™
• Intramuscular or subcutaneous injection every
3 months
Goldberg AB. Contraceptive Technology. 2007;
Mechanism of Action: DMPA
Prevents
Ovulation
Goldberg AB. Contraceptive Technology. 2007.
Reduces
production of
estradiol
Candidates for DMPA
• Women who want reversible, non-daily
contraception
▪
The percentage of teens who use DMPA increased
from 10% in 1995 to 21% in 2002
• Women in whom estrogen is contraindicated
• Women who experience menorrhagia,
dysmenorrhea, and iron deficiency anemia
• Women who don’t wish to conceive
immediately after discontinuing this method
Cromer BA. Am J Obstet Gynecol. 2005.; Westhoff C. Contraception. 2003.; Trussell J.
Contraceptive Technology. 2007.
DMPA: Failure Rate
Perfect Use
Typical Use
0.3%
3%
Westhoff C. Contraception. 2003.; Cromer BA. Am J Obstet Gynecol. 2005.
Risks and Side Effects of DMPA
Weight
Gain
Menstrual
cycle
changes
Nelson AL. J Reprod Med. 1996.; Kaunitz AM, Contraception. 2008.
BMD
Loss
Advantages of DMPA
Convenient, discrete, very effective, reversible
May improve menorrhagia, dysmenorrhea, iron
deficiency anemia, and endometriosis
Women with contraindications to estrogen can use it
Reduces the risk of endometrial cancer
Reduces risk of PID and uterine leiomyomata
Can decrease the number and severity of crises in
patients who have sickle cell anemia
Can decrease frequency of seizures
Thomas DB. Contraception. 1995.; Gray PH. Br J Obstet Gynecol. 1996.; Lumbiganon
P J Reprod Med. 1996; Culling VE. J Reprod Med. 1996.; Mattson RH Neurology.
1984.
Disadvantages of DMPA
Requires visit to clinician
Initial irregular bleeding
Weight gain
Short-term, reversible BMD loss
Delayed return to fertility
Lack of protection against STIs
Westhoff C. Contraception. 2003.; Risser WL. Adolesc Health. 2003. Le YL. Obstet
Gynecol. 2009.; Kaunitz AM, Contraception. 2008.
Contraindications
• History of or current breast cancer
• Anorexia nervosa
• Chronic steroid use
WHO. 2004
DPMA Black Box Warning
“It is unknown if use of DMPA Contraceptive
Injections during adolescence or early adulthood, a
critical period of bone accretion, will reduce peak
bone mass and increase the risk for osteoporotic
fracture in later life.
FDA Safety Alert. 2009.; Liang BA J Clin Anesth. 2002.
DPMA Black Box Warning
Prolonged use may result in
significant loss of bone density
Degree of loss is proportional to the
amount of time on DMPA
Loss may not be completely reversible
more…
FDA Safety Alert. 2009
DPMA Black Box Warning (continued)
Woman should use DepoProvera for more than two years
only if other contraceptive
methods are inadequate
FDA Safety Alert. 2009
What the Best Science Indicates
• BMD loss associated with DMPA is
similar to that associated with
pregnancy and breastfeeding
• BMD loss is substantially reversed after
stopping use of DMPA
• Environmental factors, such as
nutrition and exercise, have a more
substantial impact on bone mass than
DMPA
Kaunitz AM. Contraception. 2008.
What we know about DMPA and it’s
impact on BMD and skeletal health
DMPA users are likely to have a reduced BMD
Suppressed estradiol production is associated with
an increased rate of bone resorption
Short-term diminishment of BMD recovers within
three years once DMPA is discontinued
DMPA use not linked to the development of
menopausal osteoporotic fractures
Cundy T. BMJ. 1991.; Kaunitz AM. Obstet Gynecol Clin North Am. 2000.;
Kaunitz AM. Contraception. 2008.; Banks E. BJOG. 2001.; Westhoff CL. Contraception. 2003.;
et al.
More Research on DMPA and It’s
Impact on BMD
• Former users of DMPA had BMD similar to
nonusers
• Adolescents demonstrated a full recovery of
BMD within one year after discontinuation of
DMPA
Pettiti DB. Obstet Gynecol. 2000.; Scholes D. Arch Pediatr Adolesc Med. 2005.
“Add-back” Estrogen or DEXA scans
for Minors
Research indicates
• Estradiol levels mediate
BMD changes in adult and
adolescent DMPA users
• “Add-back” estrogen
prevents the transient
decline in the BMD of
current DMPA users
• BMD recovers after DMPA is
discontinued
• Unlikely that women would
benefit from estrogen
supplementation or serial
surveillance by DEXA scans
more…
Cundy T. J Clin Endocrinol Metab. 2003.; Kaunitz AM. Contraception. 1999.
“Add-back” Estrogen or DEXA scans
for Minors (continued)
• In adolescents, daily intake of 1500 mg
of calcium and 400 mg of vitamin D is
recommended
Guidance on DMPA Usage and
Skeletal Health
Position statements have been issued by several
professional organizations—ACOG & WHO
These organizations recommend no restrictions on
initiation or continuation of DMPA to address skeletal
health concerns
These organizations recommend no routine BMD
testing for DMPA users
Kaunitz AM. Contraception. 2008.
DMPA: ACOG Guidelines
“Concerns regarding the effect of DMPA on
BMD should neither prevent practitioners from
prescribing DMPA nor limit its use to 2
consecutive years.”
No need to perform BMD monitoring solely in
response to DMPA use.
more…
ACOG Committee Opinion No. 415. Obstet Gynecol. 2008; AAP Policy Statement.
Pediatrics. 2007.
DMPA: ACOG Guidelines (continued)
ACOG recommends:
• Counsel thoroughly about benefits and risks
of DMPA
• Encourage daily exercise and ageappropriate calcium and vitamin D intake
• Estrogen supplementation during DMPA use
is not currently recommended
ACOG Committee Opinion No. 415. Obstet Gynecol. 2008; AAP Policy Statement.
Pediatrics. 2007.
DMPA: WHO Guidelines
• No restriction on DMPA in eligible women
18-45 yrs of age
• Among adolescents and women >45 yrs
of age, advantages of DMPA generally
outweigh theoretical safety concerns re:
fracture risk
• No restrictions on progestin-only or
combined hormonal contraception in
eligible women
D’Arcangues C. Contraception. 2006.
Counseling Messages for DMPA
• Women for whom estrogen
products are contraindicated
can use DMPA
• Bleeding profile improves
over time
• Non-hormonal backup
contraception is needed for
first 7 days
What Providers Need to Know
• No mandate for serial BMD testing or “addback” estrogen supplementation
• No need to discontinue DPMA after two
years of use
• Supplemental use of menopausal doses of
estrogen can be considered for women with
additional risk factors for low BMD
• Women should consume appropriate
amounts of calcium and vitamin D. more…
FDA Safety Alert. 2009
What Providers Need to Know
(continued)
• Concerns about temporary bone loss should
be weighed against DMPA’s convenience
and efficacy
• Patients should engage in weight-bearing
exercise to promote bone health
• Risks associated with DMPA along with
genetic and lifestyle factors should be
examined
DiVasta AD. Adolesc Med. 2006.
The DMPA picture is generally rosy: