Menstrual Bleeding Changes
A change in the menstrual bleeding pattern is experienced
by most women using Norplant implants, especially during the first 90 days of use.
It is the most frequently reported side effect and includes:
- prolonged bleeding during the first few months of use,
- bleeding or spotting between menstrual periods
(intermenstrual),
- a decrease in the number of days of bleeding or spotting,
- no bleeding or spotting at all for several months
(amenorrhea), and
- a combination of any of the above.
As shown in Table 5, increased bleeding during the
first 90 days of use is common. (For comparison, 5 to 7 days of bleeding per cycle is
considered normal.)
Table 5. Changes in the Menstrual Bleeding Pattern
(first 90 days)
Changes |
% Users |
| Frequent bleeding (5+ episodes) |
21% |
| Prolonged bleeding (8+ days per
episode) |
35% |
| Numerous bleeding days (21+) |
27% |
| Numerous bleeding and spotting
days (31+) |
36% |
| Note: Some
women had more than one type of increased bleeding. |
Adapted from: United States Food and Drug
Administration 1990.
Typically, the frequency of these bleeding changes,
especially irregular and prolonged bleeding,decreases with time and is less of a problem
by the end of the first year. In one recently reported study, 234 women recorded their
bleeding patterns after implants insertion (Shoupe et al 1991). In the first year of use,
66% had irregular cycles, 27% regular and 7% amenorrheic (Figure 10). By the fifth
year of use, however, only 38% still had irregular cycles while 62% now had regular
cycles, and none were without bleeding (amenorrhea).
Figure 10. Bleeding Patterns of Norplant Implants Users
Source: Shoupe et al 1991.
In addition, both the number of bleeding and
bleeding and spotting days decreased with time (Table 6). As shown in this
table, the mean number of bleeding and spotting days during the first year was 92.3 but
decreased to 70.2 days in the fifth year (Sivin 1988).
Table 6. Bleeding and Spotting Days per Year
Year |
Bleeding
Days |
Bleeding
and Spotting Days |
Mean |
Mean |
1 |
54.3 |
92.3 |
2 |
50.3 |
79.5 |
3 |
49.1 |
76.6 |
4 |
47.6 |
72.1 |
5 |
44.1 |
70.2 |
Source: Sivin 1988.
Unfortunately, the pattern of bleeding is not predictable
in any one woman. For example, in some women the average number of bleeding and spotting
days was low in the first year but increased in years 2 to 5. For most women, however, the
number of bleeding and spotting days decreased over time (Sivin 1988).
Although initially many women report an increase in the
number of bleeding and spotting days while using Norplant implants, research has shown
that the average amount of blood loss usually is less compared with loss before using
implants. For example, in several studies hemoglobin levels have increased with continued
use of implants, and only rarely has heavy vaginal bleeding caused a significant decrease
(Sivin 1988).
Women's Reaction to Menstrual
Changes
Despite most women experiencing some change in their
menstrual bleeding pattern, the majority do not seem concerned about it. As shown in one
US clinical trial, 86% of implants users reportedmenstrual changes, but 69% were not,
or were only slightly, bothered by them (Darney et al 1990a). Thorough pre-insertion
counseling about possible changes in menstrual bleeding patterns can improve continuation.
For example, in a study of two groups of Norplant implants users, the second group which
received more counseling regarding this side effect had much higher continuation rates
(Alvarez-Sanchez, Brache and Faundes 1988).
In addition, user satisfaction studies have found that
staff attitudes and knowledge about the method, positive clinic management practices and
the availability of "user friendly" client information are important in
improving continuation of Norplant implants use (Darney 1990a).
Other Side Effects
In addition to menstrual pattern changes, several other
side effects have been reported. Most of these are similar to those seen with other POCs
and are bothersome but not serious. The most common include:
- headache (1.9%),
- weight change (usually increase) (1.7%),
- mood change (nervousness or anxiety) (1.1%),
- depression (0.9%), and
- other (nausea, change in appetite, breast tenderness,
increase in body or facial hair and acne) (1.8%).
Some of these may not be linked directly to
Norplant implants use. For example, when implants users were compared with users of IUDs
at the end of the first year, there was a similar frequency of headache, nervousness and
depression-symptoms usually associated only with hormonal contraceptive methods (Croxatto
1993). Of greater importance is that, to date, there has been noincreased risk of serious
cardiovascular (heart attack or stroke) or clotting problems, respiratory disorders or
cancer (including breast or genital) reported in implants users (Population Council 1990).
Persistent Ovarian Follicles
Enlarged ovarian follicles sometimes have been reported in
Norplant implants users as well as in women using other POCs. These are thought to be
caused by delay in the normal regression (shrinkage) of ovarian follicles which
occasionally develop. In some women these persistent follicles may grow beyond the size
they normally would reach, causing pelvic or lower abdominal discomfort. Most women,
however, are not aware of them, and they are discovered only incidentally on pelvic
examination. Because they disappear on their own in the vast majority of women, treatment
is not required unless they twist or rupture (Population Council 1990).
Reactions at the Insertion
Site
If recommended infection prevention practices are
followed, problems with healing at the insertion site are infrequent and usually occur
only in the first few weeks of use. For example, in a study involving more than 2,000
women, the infection rate was 0.8% during the first year and the rate of pain or itching
at the insertion site was only 4.7% (Population Council 1990). Therefore, with adequate
attention to pre-insertion skin preparation, use of aseptic technique and correct
placement of the capsules, the risk of infection should be very low.
Expulsion of capsules also
is uncommon. In a study involving 2,467 insertions, in only 7 women were one or more
capsules completely or partially expelled (Population Council 1990). Not unexpectedly,
this problem occurs most often when the capsules are inserted too shallow, the tips are
too close to the incision or when infection is present.
Because the incision is small (about 2 mm long), insertion
does not leave a noticeable scar in most women and the correct positioning of the capsules
subdermally makes them barely visible. In some women, however, darkening of the skin over
the insertion site occurs. This disappears when the capsules are removed.
Finally, once inserted, the capsules will not move
around and cannot break inside the arm.
A wide range of clinical studies have been conducted to
determine the pharmacologic effects of Norplant implants. To date, no clinically important
changes in carbohydrate metabolism; liver, kidney, adrenal or thyroid function; or blood
clotting mechanisms have been demonstrated (Population Council 1990).
Carbohydrates
Use of Norplant implants has been associated with a
slight, initial increase in glucose levels. Because these changes did not increase with
time, they are not felt to be clinically important (Population Council 1990).
Lipoproteins
Studies investigating the effect of LNG on serum
lipoproteins have produced variable results. For example, some studies demonstrated a
decrease in total cholesterol, triglycerides and low-density lipoproteins in Norplant
implants users while other studies have shown either transient effects or no changes. For
example, in the six studies reported in Table 7 the cholesterol to high-density
lipoproteins (HDL) ratios either improved (i.e., decreased) or were unchanged (Darney et
al 1990b).
Table 7. Effects of Levonorgestrel on Lipoprotein
Levels
| |
Singh
(1989) |
Viegas
(1988) |
Affandi
(1987) |
Roy
(1984) |
Shaaban
(1984) |
Croxatto
(1983) |
| Number of subjects |
100 |
100 |
240 |
10 |
47 |
28 |
| Cholesterol |
d |
d |
d |
n/c |
d |
d |
| Triglycerides |
d |
d |
n/c |
n/c |
d |
d |
| HDL |
n/c |
i |
n/c |
n/c |
i |
n/c |
| LDL |
d |
|
d |
n/c |
d |
d |
| Cholesterol/HDL ratio |
n/c |
d |
d |
n/c |
d |
d |
| i = increased; d =
decreased; n/c = no change |
Source: Darney et al 1990b.
Clotting Factors
Various effects on clotting factors have been reported in
Norplant implants users. These include slight changes in levels of factor VII, factor X,
antithrombin III activity, fibrinogen and platelets (Population Council 1990). The
clinical importance of these changes has yet to be determined.
Iron Metabolism
Results from clinical trials have demonstrated a general
improvement in iron concentration with Norplant implants use despite irregular
menstrual bleeding being the most common side effect. Twice as many women have shown an
increase in hemoglobin as opposed to a decrease. Furthermore, the overall increase in
hemoglobin levels is about 2% in all users (Population Council 1990).
Endocrine Changes
Serum levels of estradiol have shown non-cyclic,
irregular changes. Baseline values are normally 30 to 70 pg/ml, with occasional peaks to
200 to 400. Infrequently, peaks of up to 600 pg/ml have been measured (Population Council
1990). Furthermore, in those women having ovulatory cycles, estradiol levels are similar
to control values.
Significant decreases in circulating androstenedione,
a weak androgen, and total testosterone have been reported in Norplant implants
users. These findings are accompanied by slight decreases in sex hormone binding globulin
(SHBG). Because testosterone is tightly bound to SHBG, it is only the unbound (free)
testosterone that is biologically active. In the studies reported, the mean free
testosterone levels were essentially unchanged; therefore, it is unlikely that the effect
of levonorgestrel on androgen function is clinically important (Population Council 1990).
Endometrium
In several studies, the effect of levonorgestrel on the
lining cells of the uterus (endometrium) has been examined. Samples of endometrium from
225 women who had used implants from 2 to 116 months were examined (Population Council
1990). Microscopically, the appearance was one of mixed proliferative and secretory
activity, but a large number of biopsies showed considerable decrease in endometrial
activity (hypoplasia or atrophy)-a pattern similar to that seen in women using COCs and
POPs. In addition, no progressive changes were noted nor were there any clinically
importantpathologic changes. Based on these studies, it has been concluded that the
long-term use of LNG is not associated with any hazardous effects on the endometrium.
