Depo-SubQ Provera

WARNING: LOSS OF BONE MINERAL DENSITY • Women who use depo-subQ provera 104 may lose significant bone mineral density. Bone loss is greater with increasing duration of use and may not be completely reversible [see Warnings and Precautions (5.1) ] . • It is unknown if use of depo-subQ provera 104 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 [see Warnings and Precautions (5.1) ] . • Depo-subQ provera 104 is not recommended as a long-term (i.e., longer than 2 years) birth control method or medical therapy for endometriosis-associated pain unless other options are considered inadequate [see Indications and Usage (1) and Warnings and Precautions (5.1) ] . WARNING: LOSS OF BONE MINERAL DENSITY See full prescribing information for complete boxed warning . • Women who use depo-subQ provera 104 may lose significant bone mineral density. Bone loss is greater with increasing duration of use and may not be completely reversible. ( 5.1 ) • It is unknown if use of depo-subQ provera 104 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. ( 5.1 ) • Depo-subQ provera 104 is not recommended as a long-term (i.e., longer than 2 years) birth control method or medical therapy for endometriosis-associated pain unless other options are considered inadequate. ( 1 , 5.1 )

5 WARNINGS AND PRECAUTIONS • Thromboembolic disorders: Discontinue depo-subQ provera 104 in patients who develop arterial or venous thrombosis. ( 5.2 ) • Breast cancer risks: Monitor women with a family history of breast cancer or a significant risk of breast cancer carefully. ( 5.3 ) • Meningioma: Discontinue depo-subQ provera 104 if meningioma is diagnosed. Monitor patients for signs and symptoms of meningioma. ( 5.4 ) • Ectopic pregnancy: Consider ectopic pregnancy if a woman becomes pregnant or complains of severe abdominal pain. ( 5.5 ) • Anaphylaxis: Provide emergency medical treatment. ( 5.6 ) • Injection site reactions (e.g., persistent atrophy, dimpling/indentation, lump/nodule and discoloration) have been reported. ( 5.11 ) • Diabetics may be at greater risk of hyperglycemia. ( 5.13 ) • Jaundice and elevated transaminase: Discontinue depo-subQ provera 104 if jaundice or elevated transaminase levels develop. ( 5.14 ) 5.1 Loss of Bone Mineral Density Use of depo-subQ provera 104 reduces serum estrogen levels and is associated with significant loss of bone mineral density (BMD). This loss of BMD is of particular concern during adolescence and early adulthood, a critical period of bone accretion. It is unknown if use of depo-subQ provera 104 by younger women will reduce peak bone mass and increase the risk for osteoporotic fracture in later life. A study to assess the reversibility of loss of BMD in adolescents was conducted with DMPA-IM. After discontinuing DMPA-IM in these adolescents, mean BMD loss at the total hip and femoral neck did not fully recover by 5 years (60 months) post-treatment in the sub-group of adolescents who were treated for more than 2 years [see Clinical Studies (14.4) ] . Similarly, in adults, there was only partial recovery of mean BMD at the total hip, femoral neck, and lumbar spine towards baseline by 2 years post-treatment [see Clinical Studies (14.3) ] . The use of depo-subQ provera 104 is not recommended as a long-term (i.e., longer than 2 years) birth control method or medical therapy for endometriosis-associated pain unless other options are considered inadequate. BMD should be evaluated when a woman needs to continue to use depo-subQ provera 104 long-term. In adolescents, interpretation of BMD results should take into account patient age and skeletal maturity. Other birth control methods or therapies for endometriosis-associated pain should be considered in the risk/benefit analysis for the use of depo-subQ provera 104 in women with osteoporosis risk factors. Depo-subQ provera 104 can pose an additional risk in patients with risk factors for osteoporosis (e.g., metabolic bone disease, chronic alcohol and/or tobacco use, anorexia nervosa, strong family history of osteoporosis, or chronic use of drugs that can reduce bone mass such as anticonvulsants or corticosteroids). 5.2 Arterial and Venous Thromboembolic Disorders There have been reports of serious arterial and venous thrombotic events in women treated with DMPA-IM. Women with a history of thromboembolic disorders were not studied in clinical trials of depo-subQ provera 104. Although no causal relationship between the use of depo-subQ provera 104 and thrombotic events has been clearly established, patients who develop arterial or venous thrombosis while taking depo-subQ provera 104 should discontinue treatment. Do not re-administer depo-subQ provera 104 pending examination if there is a sudden onset of a suspected vascular ocular event (e.g., partial or complete loss of vision, proptosis, or diplopia) or migraine. Do not re-administer depo-subQ provera 104 if examination reveals papilledema or retinal vascular lesions. 5.3 Cancer Risks Breast Cancer The use of hormonal contraceptives, including depo sub-Q provera 104, is contraindicated in women who have or have had breast cancer because breast cancer may be sensitive to hormones [see Contraindications (4) ] . Women who have a family history of breast cancer or a significant risk of breast cancer should be monitored. The results of five large case-control studies assessing the association between DMPA-IM use and the risk of breast cancer are summarized in Figure M. Three of the studies suggest a slightly increased risk of breast cancer in the overall population of users; these increased risks were statistically significant in one study. One US study 1 evaluated the timing and duration of use and found a statistically significant increased risk of breast cancer in recent DMPA-IM users (defined as last use within the past five years) who used DMPA-IM for 12 months or longer; this is consistent with results of a previous study 2 . Figure M. Risk Estimates of Breast Cancer in DMPA-IM Users Odds ratio estimates were adjusted for the following covariates: Lee et al. (1987): age, parity, and socioeconomic status. Paul et al. (1989): age, parity, ethnic group, and year of interview. WHO (1991): age, center, and age at first live birth. Shapiro et al. (2000): age, ethnic group, socioeconomic status, and any combined estrogen/progestogen oral contraceptive use. Li et al. (2012): age, year, BMI, duration of OC use, number of full-term pregnancies, family history of breast cancer, and history of screening mammography. Odds Ratio [95% confidence interval (CI)] displayed on logarithmic scale Based on the published SEER-18 2015 incidence rate (age-adjusted to the 2000 US Standard Population) of breast cancer for US women, all races, age 20 to 49 years, a doubling of risk would increase the incidence of breast cancer in women who use DMPA-IM from about 73 to about 146 cases per 100,000 women. Figure M Other Cancers The relative rate of invasive squamous-cell cervical cancer in women who ever used DMPA-IM was estimated to be 1.11 (95% CI: 0.96 to 1.29). No trends in risk with duration of use or times since initial or most recent exposure were observed. Long-term, case-controlled surveillance of users of DMPA-IM found no overall increased risk of ovarian or liver cancer. 5.4 Meningioma Cases of meningiomas have been reported following repeated administration of medroxyprogesterone acetate, primarily with long term use. Monitor patients on depo-subQ provera 104 for signs and symptoms of meningioma. Discontinue depo-subQ provera 104 if a meningioma is diagnosed. 5.5 Ectopic Pregnancy Healthcare professionals should be alert to the possibility of an ectopic pregnancy among women using depo-subQ provera 104 who become pregnant or complain of severe abdominal pain. 5.6 Anaphylaxis Serious anaphylactic reactions have been reported in women using depo-subQ provera 104. If an anaphylactic reaction occurs, appropriate emergency medical treatment should be administered. 5.7 Fluid Retention Because progestational drugs including depo-subQ provera 104 may cause fluid retention, monitor patients with conditions that might be affected by fluid retention. 5.8 Weight Gain Weight gain is a common occurrence in women using depo-subQ provera 104. In three large clinical trials using depo-subQ provera 104, the mean weight gain was 3.5 lb (1.6 kg) in the first year of use. In a small, two-year study comparing depo-subQ provera 104 to DMPA-IM, the mean weight gain observed for women using depo-subQ provera 104 [7.5 lb (3.4 kg)] was similar to the mean weight gain for women using DMPA-IM [7.6 lb (3.5 kg)]. Although there are no data related to weight gain beyond 2 years for depo-subQ provera 104, the data on DMPA-IM may be relevant. In a clinical study, after five years, 41 women using Depo-Provera CI (150 mg) had a mean weight gain of 11.2 lb (5.1 kg), while 114 women using non-hormonal contraception had a mean weight gain of 6.4 lb (2.9 kg). 5.9 Delayed Return of Ovulation or Fertility Return to ovulation is likely to be delayed after stopping depo-subQ provera 104, as demonstrated in a study of 15 women who received multiple doses of depo-subQ provera 104: • Median time to ovulation was 10 months after the last injection. • Earliest return to ovulation was 6 months after the last injection. • 12 women (80%) ovulated within 1 year of the last injection. However, ovulation has occurred as early as 14 weeks after a single dose of depo-subQ provera 104; therefore, administer the next depo-subQ provera 104 12 to 14 weeks after the last injection. Return to fertility also is likely to be delayed after stopping therapy. Among 28 women using depo-subQ provera 104 for contraception who stopped treatment to become pregnant, 7 women were lost to follow-up. One woman became pregnant within one year of her last injection and another woman became pregnant 443 days after her last injection. The remaining 19 women had not become pregnant; it is not known if these 19 women were still attempting to become pregnant or if they had started a new contraceptive method . 5.10 Depression Depression (3% of depo-subQ provera 104-treated patients) and other mood disorders have been reported in clinical trials of depo-subQ provera 104 [see Adverse Reactions (6.1) ] . Patients with a history of depression or who are on treatment for depression may be at increased risk for depression recurrence or exacerbation and for associated mood disorders while receiving depo-subQ provera 104. Therefore, patients should be monitored for symptoms of depression and mood changes. 5.11 Injection Site Reactions In five clinical studies of depo-subQ provera 104 involving 2325 women (282 treated for up to 6 months, 1780 treated for up to 1 year, and 263 women treated for up to 2 years), 5% of women reported injection site reactions (such as pain/tenderness, nodule/lump, lipodystrophy, discoloration), and 1% had persistent atrophy/indentation/dimpling [see Adverse Reactions (6.1) ] . These injection site reactions have also been reported in post-marketing experience. 5.12 Bleeding Irregularities Most women using depo-subQ provera 104 experienced changes in menstrual bleeding patterns, such as amenorrhea, irregular unpredictable spotting or bleeding, prolonged spotting or bleeding, or heavy bleeding [see Adverse Reactions (6.1) ] . Fewer women experienced irregular bleeding and more experienced amenorrhea with longer term use of depo‑subQ provera 104, consistent with expected endometrial thinning effects. In three contraception trials, 39% of 2053 depo-subQ provera 104-treated women experienced amenorrhea during Month 6, and 57% experienced amenorrhea during Month 12. In two endometriosis trials using depo-subQ provera 104, 24% of 289 women experienced amenorrhea during Month 6 [see Adverse Reactions (6.1) ] . If abnormal bleeding is persistent or severe, evaluate the patient for underlying pathology or pregnancy. 5.13 Risk of Hyperglycemia in Patients with Diabetes Some patients receiving progestins may exhibit a decrease in glucose tolerance; therefore, patients with diabetes may be at greater risk of hyperglycemia. 5.14 Jaundice and Elevated Transaminase Discontinue depo-subQ provera 104 if jaundice or elevated transaminase levels develop. Depo-subQ provera 104 may be resumed after both the jaundice and elevated transaminase levels resolve, and the healthcare professional determines that depo-subQ provera 104 did not cause the abnormalities. 5.15 Protection Against Sexually Transmitted Infections Patients should be counseled that this product does not protect against HIV infection (including AIDS) and other sexually transmitted infections.

<table styleCode="Noautorules" width="100%"><col width="100%"/><thead><tr><th align="center" valign="top"><content styleCode="bold">Figure M. Risk Estimates of Breast Cancer in DMPA-IM Users</content></th></tr></thead><tfoot><tr><td align="left" colspan="1" valign="top">Odds ratio estimates were adjusted for the following covariates: Lee et al. (1987): age, parity, and socioeconomic status. Paul et al. (1989): age, parity, ethnic group, and year of interview. WHO (1991): age, center, and age at first live birth. Shapiro et al. (2000): age, ethnic group, socioeconomic status, and any combined estrogen/progestogen oral contraceptive use. Li et al. (2012): age, year, BMI, duration of OC use, number of full-term pregnancies, family history of breast cancer, and history of screening mammography.</td></tr></tfoot><tbody><tr><td align="center" valign="top"><paragraph>Odds Ratio [95% confidence interval (CI)] displayed on logarithmic scale</paragraph></td></tr><tr><td valign="top"><renderMultiMedia ID="id807" referencedObject="MM13"/></td></tr></tbody></table>

6 ADVERSE REACTIONS The following important adverse reactions are described in more detail in other sections of the prescribing information: • Loss of bone mineral density [see Warnings and Precautions (5.1) ] • Arterial and venous thromboembolic disorders [see Warnings and Precautions (5.2) ] • Anaphylaxis [see Warnings and Precautions (5.6) ] • Fluid retention [see Warnings and Precautions (5.7) ] • Delayed return of ovulation or fertility [see Warnings and Precautions (5.9) ] • Depression [see Warnings and Precautions (5.10) ] • Injection site reactions [see Warnings and Precautions (5.11) ] • Bleeding irregularities [see Warnings and Precautions (5.12) ] Most common adverse reactions (incidence >5%) are dysfunctional uterine bleeding, headache, increased weight, amenorrhea, and injection site reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Clinical trials are conducted under widely varying conditions, therefore adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to depo-subQ provera 104 in five clinical trials involving 2325 women including 2043 women who received treatment for contraception (1780 treated up to 1 year and 263 treated for up to 2 years) and 282 women for endometriosis for up to 6 months. In these pooled trials, 9% of women discontinued treatment due to an adverse reaction and the most common reason for discontinuation was dysfunctional uterine bleeding (3%). Adverse Reactions in the Contraception Adult Studies Table 1 presents frequently reported adverse reactions (>1%) in the contraception pooled studies. In these studies, the most frequently reported adverse reactions (>5%) were dysfunctional uterine bleeding (e.g., irregular, increased, decreased, or spotting), headache, increased weight, amenorrhea, and injection site reactions (e.g., pain/tenderness, nodule/lump, persistent atrophy/indentation/dimpling or lipodystrophy). The frequency reported is based on the all-causality incidence in the pooled results of the three contraception studies. Closely related "Adverse Reaction" terms were grouped but individual patients reporting two or more grouped events were only counted once. Table 1. Frequently Reported Adverse Reactions in the Contraception Studies (>1%) Adverse Reaction Frequency Dysfunctional uterine bleeding (irregular, increase, decrease, spotting) 18% Headache 9% Increased weight (see below) 7% Amenorrhea 6% Injection site reactions (such as pain/tenderness, nodule/lump, persistent atrophy/indentation/dimpling, lipodystrophy, discoloration) 6% Vaginitis, including candidiasis and bacterial 5% Abdominal pain 4% Urinary tract infections 4% Acne 4% Depression 3% Decreased libido 3% Nausea 3% Back pain 3% Breast pain/tenderness 2% Fatigue 2% Anxiety 1% Irritability 1% Dizziness 1% Dysfunctional Uterine Bleeding The extent of bleeding and spotting in the three contraception trials is presented in Figure N; data from the endometriosis trials are presented in Figure O [see Warnings and Precautions (5.1) ]. Figure N. Mean Number of Bleeding or Spotting Days in the Subgroup of Women with Bleeding or Spotting Among Women Treated with depo-subQ provera 104 in Contraception Studies N=Number of subjects with bleeding or spotting during indicated month. Figure O. Mean Number of Bleeding or Spotting Days in the Subgroup of Women with Bleeding or Spotting Among Women Treated with depo-subQ provera 104 in Endometriosis Studies N=Number of subjects with bleeding or spotting during indicated month. Figure N Figure O Weight Gain In three large clinical trials, the mean weight gain in depo-subQ provera 104 treated patients was 3.5 lb (1.6 kg) in the first year of use. Half (50%) of women remained within 4.9 lb (2.2 kg) of their initial body weight; 12% of women lost more than 4.9 lb (2.2 kg), and 38% of women gained more than 5.1 lb (2.3 kg). In a small, 2-year study comparing depo-subQ provera 104 to DMPA-IM, the mean weight gain observed for women using depo-subQ provera 104 [7.5 lb (3.4 kg)] was similar to the mean weight gain for women using DMPA-IM [7.7 lb (3.5 kg)]. Other Adverse Reactions Observed in Contraception Clinical Trials with depo-subQ provera 104 Other adverse reactions occurring at an incidence of <1% in women who received depo-subQ provera 104 were as follows: • Neoplasms benign, malignant and unspecified (including cysts and polyps): breast lump • Blood and lymphatic system disorders: anemia • Immune system disorders: drug hypersensitivity • Metabolism and nutrition disorders: weight decreased, fluid retention • Nervous system disorders: facial palsy, syncope, paresthesia, somnolence • Cardiac disorders: tachycardia • Vascular disorders: hot flushes • Respiratory, thoracic and mediastinal disorders: asthma, dyspnea • Gastrointestinal disorders: diarrhea, abdominal distension • Skin and subcutaneous tissue disorders: urticaria, pruritus, dry skin • Reproductive system and breast disorders: dysmenorrhea, galactorrhea, dyspareunia • General disorders and administration site conditions: chest pain Adverse Reactions in the Endometriosis Adult Studies The safety profile of depo-subQ provera 104 in endometriosis clinical trials was similar to the safety profile of depo-subQ provera 104 in the contraception studies with the exception of the following adverse reactions which were more frequently reported in patients with endometriosis: abdominal pain, diarrhea, nausea, and back pain. In endometriosis studies, subjects recorded daily the occurrence and severity of hot flushes. Of the depo-subQ provera 104 users, 29% reported experiencing moderate or severe hot flushes at baseline, 36% at Month 3, and 27% at Month 6. Of the leuprolide users, 33% reported experiencing moderate or severe hot flushes at baseline, 74% at Month 3, and 69% at Month 6. Adverse Reactions in the Adolescent Contraception Study Depo-sub-Q provera 104 and DMPA-IM clinical trials reported similar safety profiles in adult study populations (see Table 1 above). Accordingly, a similar safety profile is expected for adolescents receiving depo-subQ provera 104 as for adolescents receiving DMPA-IM. The safety profile of DMPA-IM for prevention of pregnancy in adolescents was observed to be generally similar to the safety profile of adult women using DMPA-IM for prevention of pregnancy, with the exception of the following adverse reactions which were reported more frequently by adolescents: abdominal pain, diarrhea, back pain, weight increased, depression, headache, and dysmenorrhea. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of DMPA-IM. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure: • Immune system disorders: anaphylactic reaction, anaphylactoid reaction, angioedema • Vascular disorders: pulmonary embolism, deep vein thrombosis, thrombophlebitis • Musculoskeletal and connective tissue disorders: osteoporosis (including osteoporotic fractures) • Reproductive system and breast disorders: prolonged anovulation, unexpected pregnancy, uterine hyperplasia • Respiratory, thoracic and mediastinal disorders: hoarseness • Skin and subcutaneous tissue disorders: increased body odor • Gastrointestinal disorders: gastrointestinal disturbances • General disorders and administration site conditions: axillary swelling, chills, thirst

<table ID="table1" width="100%"><caption>Table 1. Frequently Reported Adverse Reactions in the Contraception Studies (&gt;1%)</caption><col width="80%"/><col width="20%"/><thead><tr><th align="left" styleCode="Rrule Botrule Lrule Toprule " valign="top"><content styleCode="bold">Adverse Reaction</content></th><th align="center" styleCode="Rrule Botrule Toprule " valign="top"><content styleCode="bold">Frequency</content></th></tr></thead><tbody><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Dysfunctional uterine bleeding (irregular, increase, decrease, spotting)</paragraph></td><td align="center" styleCode="Rrule Toprule Botrule " valign="top"><paragraph>18%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Headache</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Increased weight (see below)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>7%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Amenorrhea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Injection site reactions (such as pain/tenderness, nodule/lump, persistent atrophy/indentation/dimpling, lipodystrophy, discoloration)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Vaginitis, including candidiasis and bacterial</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Abdominal pain</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Urinary tract infections</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Acne</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Depression</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased libido</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Back pain</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Breast pain/tenderness</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Fatigue</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Anxiety</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Irritability</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1%</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph>Dizziness</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1%</paragraph></td></tr></tbody></table>

<table ID="_RefID0EVEAG" styleCode="Noautorules" width="100%"><caption>Figure N. Mean Number of Bleeding or Spotting Days in the Subgroup of Women with Bleeding or Spotting Among Women Treated with depo-subQ provera 104 in Contraception Studies</caption><col width="100%"/><tfoot><tr><td align="left" colspan="1" valign="top">N=Number of subjects with bleeding or spotting during indicated month.</td></tr></tfoot><tbody><tr><td valign="top"><renderMultiMedia ID="id1087" referencedObject="MM14"/></td></tr></tbody></table>

<table ID="_RefID0EHFAG" styleCode="Noautorules" width="100%"><caption>Figure O. Mean Number of Bleeding or Spotting Days in the Subgroup of Women with Bleeding or Spotting Among Women Treated with depo-subQ provera 104 in Endometriosis Studies</caption><col width="100%"/><tfoot><tr><td align="left" colspan="1" valign="top">N=Number of subjects with bleeding or spotting during indicated month.</td></tr></tfoot><tbody><tr><td valign="top"><renderMultiMedia ID="id1097" referencedObject="MM15"/></td></tr></tbody></table>