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2. ESTIMATES OF MORTALITY FROM CONTRACEPTIVE USE
One study gathered data from a variety of sources which have estimated the mortality rate associated with different methods of contraception at different ages (Table IV). These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risks. The study concluded that with the exception of oral contraceptive users 35 and older who smoke and 40 and older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth.
The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970's -but not reported until 1983 (35). However, current clinical practice involves the use of lower estrogen formulations combined with careful consideration of risk factors. Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed (100,101), the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy non-smoking women (even with the newer low-dose formulations), there are also greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception.
Therefore, the Committee recommended that the benefits of low-dose oral contraceptive use by healthy non-smoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take the lowest possible dose formulation that is effective.
TABLE IV: ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NON-STERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE
Method of control 15Ð 19 20Ð 24 25Ð 29 30Ð 34 35Ð 39 40Ð 44 and outcome
No fertility 7.0 7. 4 9.1 14.8 25.7 28.2 control methods*
Oral contraceptives 0.3 0. 5 0.9 1. 9 13.8 31.6 non-smoker**
Oral contraceptives 2.2 3. 4 6.6 13.5 51.1 117.2 smoker**
IUD** 0.8 0. 8 1.0 1. 0 1.4 1. 4
Condom* 1. 1 1.6 0. 7 0.2 0. 3 0.4
Diaphragm/ spermicide* 1.9 1. 2 1.2 1. 3 2.2 2. 8
Periodic abstinence* 2.5 1. 6 1.6 1. 7 2.9 3. 6
*Deaths are birth related ** Deaths are method related
Adapted from H. W. Ory, ref. #35. 3. CARCINOMA OF THE REPRODUCTIVE ORGANS AND BREASTS Text Continues Below
Numerous epidemiologic studies have been performed on the incidence of breast, endometrial, ovarian, and cervical cancer in women using oral contraceptives. While there are conflicting reports, most studies suggest that the use of oral contraceptives is not associated with an overall increase in the risk of developing breast cancer. Some studies have reported an increased relative risk of developing breast cancer, particularly at a younger age. This increased relative risk appears to be related to duration of use (36Ð 43, 79Ð 89).
Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intra-epithelial neoplasia in some populations of women (45Ð 48). However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. 4. HEPATIC NEOPLASIA
Benign hepatic adenomas are associated with oral contraceptive use, although the incidence of benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases/ 100,000 for users, a risk that increases after four or more years of use especially with oral contraceptives of higher dose (49). Rupture of rare, benign, hepatic adenomas may cause death through intra-abdominal hemorrhage (50,51). Studies from Britain have shown an increased risk of developing hepatocellular carcinoma (52Ð 54) in long-term (> 8 years) oral contraceptive users. However, these cancers are extremely rare in the US and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than one per million users. 5. OCULAR LESIONS
There have been clinical case reports of retinal thrombosis associated with the use of oral contraceptives. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately. 6. ORAL CONTRACEPTIVE USE BEFORE OR DURING EARLY PREGNANCY
Extensive epidemiologic studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy (55Ð 57). Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned (55,56,58,59), when oral contraceptives are taken inadvertently during early pregnancy.
The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy. Oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion. It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the first missed period. Oral contra-ceptive use should be discontinued until pregnancy is ruled out. 7. GALLBLADDER DISEASE
Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens (60,61). More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal (62Ð 64). The recent findings of minimal risk may be related to the use of oral contraceptive formulations containing lower hormonal doses of estrogens and progestogens.
Q ¢ Q ¢
Q ¢ EVER-USERS (NON-SMOKERS) EVER-USERS (SMOKERS) CONTROLS (NON-SMOKERS) CONTROLS (SMOKERS) 250
200
150
100
50
0 15Ð 24 25Ð 34 35Ð 44 45Ð
AGE MORTALITY RATE
(NO. OF DEATHS/ 100,000
WOMAN-YEARS) 8. CARBOHYDRATE AND LIPID METABOLIC EFFECTS
Oral contraceptives have been shown to cause a decrease in glucose tolerance in a significant percentage of users (17). Oral contraceptives containing greater than 75 micrograms of estrogens cause hyperinsulinism, while lower doses of estrogen cause less glucose intolerance (65). Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents (17,66). However, in the non-diabetic woman, oral contraceptives appear to have no effect on fasting blood glucose (67). Because of these demonstrated effects, prediabetic and diabetic women should be carefully monitored while taking oral contraceptives. A small proportion of women will have persistent hypertriglyceridemia while on the pill. As discussed earlier (see WARNINGS), changes in serum triglycerides and lipopro-tein levels have been reported in oral contraceptive users. 9. ELEVATED BLOOD PRESSURE
An increase in blood pressure has been reported in women taking oral contraceptives (68) and this increase is more likely in older oral contraceptive users (69) and with continued use (61). Data from the Royal College of General Practitioners (12) and subsequent randomized trials have shown that the incidence of hypertension increases
with increasing quantities of progestogens. Women with a history of hypertension or hypertension-related diseases, or renal disease (70) should be encouraged to use another method of contraception. If women elect to use oral contraceptives, they should be monitored closely and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued. For most women, elevated blood pressure will return to normal after stopping oral contraceptives (69), and there is no difference in the occurrence of hypertension between ever-and never-users (68,70,71). 10. HEADACHE
The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent, or severe requires discontinuation of oral contraceptives and evaluation of the cause. 11. BLEEDING IRREGULARITIES
Breakthrough bleeding and spotting are sometimes encountered in patients on oral con-traceptives, especially during the first three months of use. Non-hormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or preg-nancy in the event of breakthrough bleeding, as in the case of any abnormal vaginal bleeding. If pathology has been excluded, time or a change to another formulation may solve the problem. In the event of amenorrhea, pregnancy should be ruled out. Some women may encounter post-pill amenorrhea or oligomenorrhea, especially when such a condition was pre-existent. 12. ECTOPIC PREGNANCY
Ectopic as well as intrauterine pregnancy may occur in contraceptive failures. PRECAUTIONS 1. GENERAL
Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases. 2. PHYSICAL EXAMINATION AND FOLLOW UP
It is good medical practice for all women to have annual history and physical examinations, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen, and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed,
persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care. 3. LIPID DISORDERS
Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult. 4. LIVER FUNCTION
If jaundice develops in any woman receiving such drugs, the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired
liver function. 5. FLUID RETENTION
Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions
which might be aggravated by fluid retention. 6. EMOTIONAL DISORDERS
Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree. 7. CONTACT LENSES
Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist. 8. DRUG INTERACTIONS
Reduced efficacy and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin. A similar association, though less marked, has been suggested with barbiturates, phenyl-butazone, phenytoin sodium, carbamazepine and possibly with griseofulvin, ampicillin,
and tetracyclines (72). 9. INTERACTIONS WITH LABORATORY TESTS
Certain endocrine and liver function tests and blood components may be affected by oral contraceptives: a. Increased prothrombin and factors VII, VIII, IX and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability. b. Increased thyroid binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 by column or by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered. c. Other binding proteins may be elevated in serum. d. Sex hormone-binding globulins are increased and result in elevated levels of total circulating sex steroids; however, free or biologically active levels either decrease or remain unchanged. e. High-density lipoprotein cholesterol (HDL-C) and triglycerides may be increased, while low-density lipoprotein cholesterol (LDL-C) and total cholesterol (Total-C) may be decreased or unchanged. f. Glucose tolerance may be decreased. g. Serum folate levels may be depressed by oral contraceptive therapy. This may be of clinical significance if a woman becomes pregnant shortly after discontinuing oral contraceptives. 10. CARCINOGENESIS
See WARNINGS section. 11. PREGNANCY Pregnancy Category X (see CONTRAINDICATIONS and WARNINGS sections). 12. NURSING MOTHERS
Small amounts of oral contraceptive steroids have been identified in the milk of nursing mothers and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completely weaned her child. 13. PEDIATRIC USE
Safety and efficacy of Mircette ® (desogestrel/ ethinyl estradiol and ethinyl estradiol) Tablets have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated. GENERAL PRECAUTIONS 1. Missed periods and use of oral contraceptives before or during early pregnancy There may be times when you may not menstruate regularly after you have completed taking a cycle of pills. If you have taken your pills regularly and miss one menstrual period, continue taking your pills for the next cycle but be sure to inform your doctor or health care provider before doing so. If you have not taken the pills daily as instructed and missed a menstrual period, or if you missed two consecutive menstrual periods, you may be pregnant. Check with your doctor or health care provider immediately to determine whether you are pregnant. Do not continue to take oral contraceptives until you are sure you are not pregnant, but continue to use another method of contraception.
There is no conclusive evidence that oral contraceptive use is associated with an increase in birth defects, when taken inadvertently during early pregnancy. Previously, a few studies had reported that oral contraceptives might be associated with birth defects, but these studies have not been confirmed. Nevertheless, oral contraceptives or any other drugs should not be used during pregnancy unless clearly necessary and prescribed by your doctor or health care provider. You should check with your doctor or health care provider about risks to your unborn child of any medication taken during pregnancy. 2. While breast feeding If you are breast feeding, consult your doctor or health care provider before starting oral contraceptives. Some of the drug will be passed on to the child in the milk. A few adverse effects on the child have been reported, including yellowing of the skin (jaundice) and breast enlargement. In addition, oral contraceptives may decrease the amount and quality of your milk. If possible, do not use oral contraceptives while breast feeding. You should use another method of contraception since breast feeding provides only partial protection from becoming pregnant and this partial protection decreases significantly as you breast feed for longer periods of time. You should consider starting oral contraceptives only after you have weaned your child completely. 3. Laboratory tests If you are scheduled for any laboratory tests, tell your doctor or health care provider you are taking birth control pills. Certain blood tests may be affected by birth control pills. 4. Drug interactions Certain drugs may interact with birth control pills to make them less effective in preventing pregnancy or cause an increase in breakthrough bleeding. Such drugs include rifampin, drugs used for epilepsy such as barbiturates (for example, phenobarbital), phenytoin
(Dilantin ® is one brand of this drug), phenylbutazone (Butazolidin ® is one brand), and possibly certain antibiotics. You may need to use additional contraception when you take drugs which can make oral contraceptives less effective. 5. Sexually transmitted diseases This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against transmission of HIV (AIDS) and other sexually transmitted diseases such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis. HOW TO TAKE THE PILL IMPORTANT POINTS TO REMEMBER
BEFORE YOU START TAKING YOUR PILLS: 1. BE SURE TO READ THESE DIRECTIONS:
Before you start taking your pills.
Anytime you are not sure what to do. 2. THE RIGHT WAY TO TAKE THE PILL IS TO TAKE ONE PILL EVERY DAY AT THE SAME TIME.
If you miss pills you could get pregnant. This includes starting the pack late.
The more pills you miss, the more likely you are to get pregnant. 3. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1Ð 3 PACKS OF PILLS.
If you feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If it doesn't go away, check with your doctor or health care provider. 4. MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even when you make up these missed pills. On the days you take 2 pills to make up for missed pills, you could also feel a little sick to your stomach. 5. IF YOU HAVE VOMITING OR DIARRHEA, for any reason, or IF YOU TAKE SOME MEDICINES, including some antibiotics, your pills may not work as well.
Use a back-up method (such as condoms, foam, or sponge) until you check with your doctor or health care provider. 6. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your doctor or health care provider about how to make pill-taking easier or about using another
method of birth control. 7. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your doctor or health care provider. BEFORE YOU START TAKING YOUR PILLS 1. DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL.
It is important to take it at about the same time every day. 2. LOOK AT YOUR PILL PACK: IT WILL HAVE 28 PILLS:
This 28-pill pack has 26 "active" [white and yellow] pills (with hormones) and 2 "inac-tive" [green] pills (without hormones). 3. ALSO FIND: 1) where on the pack to start taking the pills,
2) in what order to take the pills (follow the arrows) and
3) the week numbers as shown in the picture below.
®
(desogestrel/ ethinyl estradiol and ethinyl estradiol) Tablets
Storage:
Store at controlled room temperature 20Ð 25 ° C (68Ð 77 ° F).
Lot/
Exp:
See bottom of pack Organon Inc., W. Orange, NJ
07052
4. BE SURE YOU HAVE READY AT ALL TIMES:
ANOTHER KIND OF BIRTH CONTROL (such as condoms, foam, or sponge) to use as a back-up in case you miss pills.
AN EXTRA, FULL PILL PACK.
WHEN TO START THE FIRST PACK OF PILLS
You have a choice of which day to start taking your first pack of pills. Decide with your doctor or health care provider which is the best day for you. Pick a time of day which will be easy to remember. DAY 1 START: 1. Pick the day label strip that starts with the first day of your period (this is the day you start bleeding or spotting, even if it is almost midnight when the bleeding begins). 2. Place this day label strip in the cycle tablet dispenser over the area that has the days of the week (starting with Sunday) imprinted in the plastic.
Note: If the first day of your period is a Sunday, you can skip steps #1 and #2. 3. Take the first "active" [white] pill of the first pack during the first 24 hours of your period. 4. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period. SUNDAY START: 1. Take the first "active" [white] pill of the first pack on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the pack that same day. 2. Use another method of birth control as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). Condoms, foam, or the sponge are good back-up methods of birth control. WHAT TO DO DURING THE MONTH 1. TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE PACK IS EMPTY.
Do not skip pills even if you are spotting or bleeding between monthly periods or feel sick to your stomach (nausea).
Do not skip pills even if you do not have sex very often. 2. WHEN YOU FINISH A PACK OR SWITCH YOUR BRAND OF PILLS:
21 pills: Wait 7 days to start the next pack. You will probably have your period during that week. Be sure that no more than 7 days pass between 21-day packs.
28 pills: Start the next pack on the day after your last pill. Do not wait any days between packs. WHAT TO DO IF YOU MISS PILLS
If you MISS 1 "active" [white] pill: 1. Take it as soon as you remember. Take the next pill at your regular time. This means you take 2 pills in 1 day. 2. You do not need to use a back-up birth control method if you have sex.
If you MISS 2 "active" [white] pills in a row in WEEK 1 OR WEEK 2 of your pack: 1. Take 2 pills on the day you remember and 2 pills the next day. 2. Then take 1 pill a day until you finish the pack. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days.
If you MISS 2 "active" [white] pills in a row in WEEK 3: 1. If you are a Day 1 Starter:
THROW OUT the rest of the pill pack and start a new pack that same day.
If you are a Sunday Starter:
Keep taking 1 pill every day until Sunday.
On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or health care provider because you might be pregnant. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days.
If you MISS 3 OR MORE "active" [white] pills in a row (during the first 3 weeks): 1. If you are a Day 1 Starter:
THROW OUT the rest of the pill pack and start a new pack that same day.
If you are a Sunday Starter:
Keep taking 1 pill every day until Sunday.
On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or health care provider because you might be pregnant. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days.
A REMINDER FOR THOSE ON 28-DAY PACKS:
If you forget any of the 2 [green] or 5 [yellow] pills in Week 4:
THROW AWAY the pills you missed.
Keep taking 1 pill each day until the pack is empty.
You do not need a back-up method.
FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED:
Use a BACK-UP METHOD anytime you have sex.
KEEP TAKING ONE "ACTIVE" [WHITE] PILL EACH DAY until you can reach your doctor or health care provider. PREGNANCY DUE TO PILL FAILURE The incidence of pill failure resulting in pregnancy is approximately one percent (i. e., one pregnancy per 100 women per year) if taken every day as directed, but more typical failure rates are about 5%. If failure does occur, the risk to the fetus is minimal. PREGNANCY AFTER STOPPING THE PILL There may be some delay in becoming pregnant after you stop using oral contraceptives, especially if you had irregular menstrual cycles before you used oral contraceptives. It may be advisable to postpone conception until you begin menstruating regularly once you have stopped taking the pill and desire pregnancy. There does not appear to be any increase in birth defects in newborn babies when pregnancy occurs soon after stopping the pill. OVERDOSAGE Serious ill effects have not been reported following ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea and withdrawal bleeding in females. In case of overdosage, contact your doctor, health care provider or pharmacist. OTHER INFORMATION Your doctor or health care provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and your doctor or the health care provider believes that it is a good medical practice to postpone it. You should be reexamined at least once a year. Be
sure to inform your doctor or health care provider if there is a family history of any of the conditions listed previously in this leaflet. Be sure to keep all appointments with your doctor or health care provider, because this is a time to determine if there are early signs of side effects of oral contraceptive use. Do not use the drug for any condition other than the one for which it was prescribed. This drug has been prescribed specifically for you; do not give it to others who may want birth
control pills. HEALTH BENEFITS FROM ORAL CONTRACEPTIVES In addition to preventing pregnancy, use of combination oral contraceptives may provide certain benefits. They are:
° menstrual cycles may become more regular.
° blood flow during menstruation may be lighter and less iron may be lost. Therefore, anemia due to iron deficiency is less likely to occur.
° pain or other symptoms during menstruation may be encountered less frequently.
° ectopic (tubal) pregnancy may occur less frequently.
° non-cancerous cysts or lumps in the breast may occur less frequently.
° acute pelvic inflammatory disease may occur less frequently.
° oral contraceptive use may provide some protection against developing two forms of cancer: cancer of the ovaries and cancer of the lining of the uterus.
If you want more information about birth control pills, ask your doctor, health care provider, or pharmacist. They have a more technical leaflet called the Prescribing Information which you may wish to read.
SUN MON TUE WED TH THU FRI SAT SUN MON TUE WED
®
(desogestrel/ ethinyl estradiol and ethinyl estradiol) Tablets
Storage: Store at controlled room temperature 20Ð 25 °C
(68Ð 77 ° F).
Lot/
Exp:
See bottom of pack Organon Inc., W. Orange, NJ 07052
THU FRI SAT SUN MON TUE WED
0206100015
0206100015
Patients should be counseled that this product does not protect against
HIV infection (AIDS) and other sexually transmitted diseases.
Manufactured for Organon
Inc. West Orange, NJ 07052
by N. V. Organon, Oss,
The Netherlands or Organon (Ireland) Ltd., Swords, Co. Dublin, Ireland
©2000
Organon Inc.
5310206
10/ 00
15
®
Manufactured for Organon Inc. West Orange, NJ 07052
by N. V. Organon, Oss, The Netherlands or
Organon (Ireland) Ltd., Swords, Co. Dublin, Ireland
©2000 Organon Inc. 5310206 10/ 00 15 2 Page: << Prev | 1 | 2 | 3 | 4 | 5
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