Clinical Use of Misoprostol in Nonpregnant Women: Review Article * Review Article

Review Article
Clinical Use of Misoprostol in Nonpregnant Women: Review Article
Chainarong Choksuchat, MD*
From the Department of Obstetrics and Gynecology, Faculty of Medicine, Prince of Songkla University, Hat-Yai, Songkhla, Thailand.
ABSTRACT Misoprostol, a prostaglandin E1 derivative, has been widely used in nonpregnant women because of its cervical ripening and
uterotonic effects. A large number of studies have demonstrated its effectiveness in enhancing ease of cervical dilation. This
review article describes its pharmacokinetic profile and the relationship between prostaglandins and cervical ripening and
uterine contraction and provides a review of the clinical use of misoprostol in nonpregnant women including cervical priming
before hysteroscopy, before insertion of an intrauterine device, in endometrium biopsy, preoperatively in myomectomy, and
before intrauterine insemination to improve pregnancy rates. Adverse effects are also described. Journal of Minimally Invasive
Gynecology (2010) 17, 449–455 Ó 2010 AAGL. All rights reserved.
Keywords:
Biopsy; Endometrium; Gynecology; Hysteroscopy; Intrauterine device; Intrauterine insemination; IUD; IUI; Misoprostol; Myomectomy
Misoprostol, a prostaglandin E1 (PGE1) derivative, was
first approved in 1988 by the US Food and Drug Administration for prevention and treatment of gastric ulcers induced by
nonsteroidal anti-inflammatory drugs [1]. It inhibits secretion
of acid and pepsin in the stomach and has a mucosal protective effect on the gastrointestinal mucosa [2].
Because of its cervical ripening and uterotonic activity
effects, misoprostol has been extensively used in obstetrics
and gynecology for several years. A website, http.//www.
misoprostol.org/, is devoted to obstetric and gynecologic
uses of misoprostol with an extensive bibliography. A large
number of studies have demonstrated its effectiveness in termination of pregnancy in the first and second trimester [3–6].
Misoprostol has also been used for induction of labor and
treatment of postpartum hemorrhage [7–9].
Misoprostol has been widely used in nonpregnant women
as well. Many authors describe using the medication for
cervical priming before hysteroscopy [10–13], before
insertion of an intrauterine device (IUD), at endometrial
biopsy [14], preoperatively in myomectomy [15], and
before intrauterine insemination (IUI) to improve pregnancy
rates [16].
The author has no commercial, proprietary, or financial interest in the
products or companies described in this article.
Corresponding author: Chainarong Choksuchat, MD, Department of Obstetrics and Gynecology, Faculty of Medicine, Prince of Songkhla University,
Hat-Yai, Songkhla 90110, Thailand.
E-mail: [email protected]
Submitted December 30, 2009. Accepted for publication March 12, 2010.
Available at www.sciencedirect.com and www.jmig.org
1553-4650/$ - see front matter Ó 2010 AAGL. All rights reserved.
doi:10.1016/j.jmig.2010.03.015
For this review, electronic searches were undertaken in
PubMed and SCOPUS using the keywords ‘‘Misoprostol,’’
‘‘Pharmacokinetics,’’ ‘‘Cervical ripening,’’ ‘‘Uterine contraction,’’ ‘‘Nonpregnant women,’’ ‘‘Hysteroscopy,’’ ‘‘Intrauterine insemination,’’ ‘‘IUI,’’ ‘‘Endometrial biopsy,’’
Intrauterine device,’’ ‘‘IUD insertion,’’ and ‘‘Myomectomy.’’
Pharmacokinetics
Misoprostol (Cytotec; G.D. Searle & Co., Skokie, IL) is
a 15-deoxy, 16-hydroxy, 16-methyl synthetic analogue of
natural PGE1 [1]. After oral administration, misoprostol is
absorbed and undergoes rapid deesterification to misoprostol
acid, its biologically active metabolite [17]. The pharmacokinetic profile is no different between pregnant and nonpregnant women [18]. Misoprostol can be administered
sublingually, orally, vaginally, or rectally. The plasma concentration of misoprostol acid peaks less than 30 minutes after administration via the oral or sublingual route in pregnant
women, after which the blood concentration decreases rapidly. Misoprostol acid levels peak approximately 1 hour after
vaginal application. After 1 dose of misoprostol administered
vaginally, the plasma concentration gradually decreases;
however, it persists for at least 6 hours at substantially higher
concentrations than when administered orally or sublingually. The area under the misoprostol acid concentration
vs time curve indicates that the systemic bioavailability of
sublingually administered misoprostol is significantly greater
than with orally or vaginally administered misoprostol. There
are no significant differences between sublingual and vaginal
450
Journal of Minimally Invasive Gynecology, Vol 17, No 4, July/August 2010
administration [19]. Rectally administered misoprostol is associated with a qualitatively similar absorption curve as that
administered vaginally, but with lower bioavailability [20].
Misoprostol was originally manufactured for oral administration. Undissolved fragments of the misoprostol tablet are
often found when administered vaginally because of incomplete dissolution [5,11,18,21,22]. Misoprostol is thought to
liquefy better in an acidic medium. However, when
compared with adding only water, Singh et al [23] failed
to demonstrate any benefits of adding acetic acid, pH 2, to
a 200-mg tablet of vaginal misoprostol administered 3 to 4
hours before vacuum aspiration for termination of firsttrimester pregnancies.
enzymes that cause the changes in the extracellular matrix
that are associated with ripening of the cervix [28].
Prostaglandins act synergistically with nitric oxide (NO),
and have an important role in cervical ripening by causing
changes in the extracellular matrix that are associated with
ripening of the cervix [29]. Nitric oxide may regulate the activity of metalloproteinases responsible for collagen degradation, and induce prostaglandin production by stimulating
cyclooxygenase activity [30].
Prostaglandin E1 can induce release of cervical NO. The
level of NO metabolites increased significantly for 1 to 3
hours after administration of 400 and 25 mg of vaginal misoprostol in early and late stages of pregnancy [31]. However,
the same study demonstrated that 400 mg of vaginal misoprostol had no effect on cervical fluid NO metabolites in
nonpregnant women. There is no information on whether
a higher dosage of misoprostol or a longer time would have
resulted in release of cervical NO in nonpregnant women.
Nevertheless, cervical ripening at approximately 10 hours
after misoprostol administration has been demonstrated in
many studies [11–13,32–35].
Prostaglandins have potent uterotonic activity caused by
their effect of increasing intracellular calcium and activating
myosin light-chain kinase, leading in turn to actin and myosin
undergoing conformational changes that enable them to slide
over each other, causing shortening of the muscle cells and
inducing uterine contractions [28].
Prostaglandins and Cervical Ripening or Uterine
Contraction
The complex biochemical process of cervical ripening and
the mediators associated with this mechanism are still largely
unknown. It has not yet been conclusively established how
prostaglandins produce cervical ripening. Ripening of the
uterine cervix is related to changes in collagen, glycosaminoglycans, and collagenolytic activity. Connective-tissue biopsy
specimens from the lower part of the uterine cervix in pregnant
women at various gestational stages have demonstrated that
the concentrations of collagen, sulfated glycosaminoglycans,
and hyaluronic acid decrease during pregnancy.
When compared with nonpregnant women, the concentrations of collagen are approximately 70% at 10 weeks of gestation, and approximately 30% at term. The collagenolytic
activity increases with advancing gestational age. The 2,4-dinitrophenyl-Pro-Gln-Gly-Ile-Ala-Gly-Gin-D-Arg hydrolytic
activity (collagenase) and the leukocyte elastase concentration increase gradually by a factor of 10. One study found
that cervical dilation time during spontaneous labor was longer in women with high concentrations of collagen, and
shorter in women with low concentrations of collagen [24].
el-Rafaey et al [25] demonstrated a similar alteration in
cervical connective tissue after vaginal administration of
misoprostol or gemeprost (an alopostadil prostaglandin
analogue) [25]. Electron microscopy and histochemical studies of cervical tissue revealed that mean proline incorporation
per microgram of protein (i.e., collagen metabolism)
increased significantly, whereas collagen density, estimated
using light intensity, decreased significantly. In addition,
the diameter of collagen fibers was smaller after PGE1
application. Dilation of the cervix at parturition in guinea
pigs also involves collagenase-mediated degradation of
cervical collagen [26].
Prostaglandins are capable of inducing production of
hyaluronic acid by cervical fibroblasts, causing increased
hydration and alteration of the composition of glycosaminoglycan and proteoglycan [27]. Prostaglandins may act as
chemotactic agents, promoting the infiltration of leukocytes
and macrophages into the cervical stroma. These inflammatory cells could be the source of the specific degradative
Use of Misoprostol in Nonpregnant Women
Preoperative Use for Hysteroscopy
Many patients require cervical dilation before hysteroscopy. There have been some reports of cervical tears, false
tracts, bleeding, or uterine perforation during the dilation procedure [36,37]. Misoprostol can be used to ripen the cervix,
resulting in a softer, more easily dilated cervical canal,
which in turn can decrease the number of women who
require further mechanical cervical dilation before surgery
[10] (Table 1).
Misoprostol in Premenopausal Women
Studies in premenopausal women have demonstrated that
baseline cervical canal diameter is significantly greater when
misoprostol is used compared with placebo groups. One
meta-analysis found that the mean cervical diameter 12 hours
after misoprostol administration was approximately 6.0 to
7.5 mm, and the need for further cervical dilation was
reduced (relative risk, 0.61; 95% confidence interval,
0.51–0.73) [10]. Clinical data from several studies suggest
that the efficacy of 200 mg of vaginal misoprostol or 400
mg of oral misoprostol is comparable with laminaria and is
more effective than dinoprostone for cervical priming before
hysteroscopy [33,39]. However, 1 study demonstrated that
more patients needed cervical dilation in a misoprostol
group compared with a group prepared with a laminaria
Choksuchat.
Use of Misoprostol in Nonpregnant Women
451
Table 1
Use of misoprostol for preoperative cervical dilation before hysteroscopy
Cervix diameter, mean (SD), mm
Mean
interval, hr
Before
medication
12
12
12
12 and 24
8
4
NA
NA
NA
NA
NA
NA
9–10
12
10–12
12
4–6
12 and 24
2
NA
2.00 (1.90)
vs 2.37 (1.83)
NA
NA
NA
NA
NA
400 PO vs placebo
400 PO vs placebo
800 Vg vs placebo
400 Vg vs placebo
1000 Vg vs placebo
200 Vg vs placebo
12
12 and 24
7
12
12
8
1000 Vg vs placebo
100 SL vs placebo
2–4
12
Source
No. of patients
Regimen, mg
Premenopause
Ngai [35]
Preutthipan [12]
Preutthipan [13]
Thomas [38]
Darwish [33]
Fernandez [34]
44
91
120
220
144
48
Preutthipan [39]
Choksuchat [11]
310
60
400 PO vs placebo
200 Vg vs placebo
200 Vg vs placebo
400 PO vs placebo
200 Vg vs laminaria
Placebo vs 200 Vg vs
400 Vg vs 800 Vg
200 Vg vs dinoprostone
400 PO vs 200 Vg
400 PO vs 400 Vg
1000 Vg vs placebo
400 Vg vs placebo
400 PO vs laminaria
200 SL vs placebo
Batukan [40]
77
Oppegaard [41]
69
Singh [42]
100
Lin [43]
117
Mulayim [44]
52
Postmenopause
Ngai [45]
37
Thomas [38]
220
Fung [46]
98
Barcaite [32]
105
Oppegaard [44]
24
da Costa [47]
120
Post-GnRH agonists administration
Cooper [48]
64
Bisharah [49]
40
After medication
6.0 (1.3) vs 3.2 (1.3)a
7.0 (1.0) vs 3.8 (1.2)a
7.3 (0.7) vs 3.8 (1.1)a
8.2 (2.3) vs 7.5 (2.2)
7.5 (1.2) vs 7.6 (1.2)
6.1 (1.4) vs 6.3 (1.4) vs
5.79 (2.0) vs 6.8 (2.1)
7.4 (0.8) vs 7.0 (0.9)a
5.10 (1.75) vs 5.60 (1.69)
Need for further
dilation, %
NA
31.1 vs 6.5
94.9 vs 75.3a
NA
NA
NA
6.0 (1.5) vs 7.3 (1.6)a
6.4 (2.4) vs 4.8 (2.0)a
NA
8.0 (3.7) vs 12.1 (3.2)
NA
70.4 vs 80.4a
3.10 (1.79)
vs 3.23 (1.74)b
94.9 vs 63.2a
NA
30 vs 22c
70.2 vs 28.3a
56 vs 77.7c
NA
NA
NA
NA
NA
NA
4.2 (1.7) vs 4.4 (1.6)
6.9 (2.2) vs 5.7 (2.7)
5.2 (1.2) vs 5.0 (1.4)
7.6 (1.4) vs 5.0 (1.1)a
3.4 (2.7) vs 4.9 (1.5)
NA
NA
NA
68.1 vs 72.9
52.9 vs 98.1a
NA
17.2 vs 20.3
NA
NA
NA
4.2 (0.2) vs 4.0 (0.1)
NA
d
NA 5 not applicable; PO 5 oral administration; SL 5 sublingual administration; Vg 5 vaginal administration.
a
p , .05.
b
Comparison of cervical width difference between oral and vaginal administration.
c
Comparison of need for cervical dilation.
d
Comparison of peak force at each diameter during dilation, and no significant difference in cervical resistance was detected.
tent [43]. Another study found that the force needed to dilate
a cervix to 6 mm was less when 400 mg of vaginal misoprostol was administered 12 to 24 hours before hysteroscopy [50].
Furthermore, in women who had undergone cesarean section
and no vaginal deliveries, 400 mg of vaginal misoprostol at 6
and 12 hours before operative hysteroscopy led to a significantly greater cervical width and fewer failed cervical
dilations than in a control group [51].
When a comparison was made between oral and vaginal
administration, 400 mg of oral misoprostol had similar efficacy in cervical ripening as 200 mg of vaginal misoprostol
[11]. However, at the same dose of 400 mg, another study
found vaginal misoprostol to be more effective than oral
misoprostol [40]. Mean (SD) cervical width in the vaginal
misoprostol group was significantly greater than in the oral
group (7.3 [1.6] mm vs 6.0 [1.5] mm). Also in this study,
the percentage of women with an initial cervical width of 9
mm was statistically significantly higher in the vaginal
misoprostol group (36.8% vs 5.1%) [40].
The time between misoprostol administration and operation may affect its efficacy. Some studies have found an interval of 4 to 6 hours between administration of misoprostol and
surgery did not alter the need for cervical dilation and it did
not facilitate hysteroscopic surgery [34,42]. Another study
found no benefit with a dose up to 800 mg at this interval
[34]. However, other studies have found that administration
of 200 to 400 mg of misoprostol 8 to 12 hours before surgery
resulted in a better outcome, with cervical width of roughly
5.6 to 7.5 mm [11–13,33,35,39,40]. One of these studies,
by Darwish et al [33], demonstrated that 8 hours after administration of 200 mg of vaginal misoprostol, the cervical diameter was comparable with the cervical diameter in women
using laminaria.
It is not necessary to increase the amount of vaginal misoprostol to prime the cervix to more than 400 mg if it is administered at least 12 hours before surgery. Studies have found
that higher dosages of misoprostol did not provide greater cervical response than lower dosages. One study found that mean
(SD) cervical dilation was 6.4 (2.4) mm vs 4.8 (2.0) mm in
a randomized controlled trial comparing 1000 mg of vaginal
misoprostol with placebo 12 hours before operative hysteroscopy [41]. The change in cervical diameter after using 200
mg of vaginal misoprostol or 400 mg of oral misoprostol 12
hours before surgery was approximately 3 mm wider. A systematic analysis in another study revealed that misoprostol
increased cervical dilation (weighted mean difference, 2.64
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Journal of Minimally Invasive Gynecology, Vol 17, No 4, July/August 2010
mm; 95% confidence interval, 1.73–3.54), and 1 in 4 premenopausal women who received misoprostol before hysteroscopy did not require further cervical dilation [10].
The incidence of cervical tears from mechanical dilation
was significantly less in 2 studies in the misoprostol group
compared with the placebo or dinoprostone groups [13,39].
The operative time in another study was significantly
shorter after cervical priming with misoprostol compared
with placebo [12,13].
In conclusion, we recommend a dose of 200 to 400 mg of
vaginal misoprostol administered 10 to 12 hours before
hysteroscopy in premenopausal women to facilitate cervical
dilation.
no benefit from 1000 mg of vaginal misoprostol administered
2 to 4 hours before hysteroscopy in a group of such women.
Although sublingual administration provides the highest
systemic bioavailability, a study showed that cervical dilation
in women using 100 mg of sublingual misoprostol at 12
hours before surgery was not different from that in a placebo
group [49].
In general, GnRH agonists induce a state of hypogonadotropic hypogonadism by downregulating the pituitary GnRH
receptors [56]. This condition also occurs in postmenopausal
women [57]. Therefore, we speculate that the effects of
misoprostol in patients receiving GnRH agonists are similar
to the effects observed in postmenopausal (hypogonadal)
women.
In conclusion, there is only limited evidence to support
a useful role for misoprostol in cervical dilation in women
receiving treatment with GnRH agonists.
Misoprostol in Postmenopausal Women
Most studies that have examined the use of misoprostol in
postmenopausal women before hysteroscopy have failed to
demonstrate any benefits [38,41,45–47]. One study showed
that administration of 400 mg of vaginal misoprostol in
perimenopausal and postmenopausal women 12 hours
before hysteroscopy produced a greater cervical diameter
and less need for further dilation than in the placebo group
[32]. In contrast, however, 3 randomized control trials
did not show any benefits with 200 or 800 mg of vaginal
misoprostol at approximately 8 hours or 1000 mg of vaginal
misoprostol at 12 hours before hysteroscopy [41,46,47]. In
addition, sequential doses of 400 mg of oral misoprostol at
12 and 24 hours before surgery did not demonstrate any
advantage insofar as cervical dilation [38].
We hypothesize that hypoestrogenic status may be related
to poor cervical response to misoprostol in postmenopausal
women because estrogen receptors are present in the human
cervix [52]. Although interstitial collagenase is believed to
have a key role in the mechanism of cervical ripening,
gonadal steroids are assumed to be involved in cervical
changes. Prostaglandin E2 interacts with gonadal steroid
receptors, and this interaction results in production of collagenase and increased remodeling of the cervical connective
tissue, involving changes to proteoglycan metabolism and
composition [53]. One study found that estradiol demonstrated a stimulative effect on the procollagenase transcription via a prostaglandin-dependent pathway in cervical
fibroblasts in guinea pigs [54]. Further evidence in support
of this assumption can be found in a study that found that
misoprostol had a greater priming effect on the estrogenpretreated cervix in postmenopausal women undergoing
endometrial curettage [55].
In conclusion, it seems that there is still not enough
evidence to support a positive effect for misoprostol on
cervical dilation in postmenopausal women.
Misoprostol and Administration of Gonadotropin-Releasing
Hormone Agonists
Few studies have examined the cervical effects of misoprostol in women receiving treatment with gonadotropinreleasing hormone (GnRH) agonists. Cooper et al [48] found
Misoprostol in IUI
Prostaglandin is thought to help transport sperm by enhancing uterine and fallopian tube contractility [16,58].
Prostaglandin E may also have an important role during the
implantation period [59]. However, this substance may be
removed from the semen during the process of sperm preparation for IUI. Brown et al [16] used vaginal misoprostol, 400
mg, mixed with 5 mL of inert triglyceride administered via
suppository at IUI and found that the cumulative pregnancy
rate with misoprostol therapy was significantly greater than
with placebo (17% vs 9% per cycle). A significant difference
was noted in clomiphene cycles but not in clomiphene/
follicle-stimulating hormone or natural cycles. However,
these same authors later reported uterine cramping, uterine
bleeding, and unfavorable pregnancy rates in patients who
received vaginal misoprostol without mixing with a triglyceride base [16]. In contrast, Moslemizadeh et al [60] did not
find any benefits of 200 mg of vaginal misoprostol in the
clomiphene citrate/human menopausal gonadotropin cycle;
clinical pregnancy rates were 15.15% vs 18.2% in the treatment and control groups, respectively. Furthermore, 400 mg
of vaginal misoprostol not only has no benefit for IUI
outcomes, but it also increases vaginal bleeding and abdominal cramping [61].
In conclusion, at this time, there is limited evidence to
support the use of misoprostol in an IUI procedure.
Misoprostol in Endometrial Biopsy
Endometrial biopsy is essential to evaluate intrauterine
disease in many gynecologic patients. In most situations,
the gynecologist must deal with a narrow cervix. Perrone
et al [14] evaluated use of 400 mg of oral misoprostol or a placebo 3 hours before an office endometrial biopsy in women
aged 35 to 77 years (mean age, approximately 46 years in
both groups). Women in the misoprostol group experienced
significant uterine cramping 1ˇ1/2 hours after the procedure,
Choksuchat.
Use of Misoprostol in Nonpregnant Women
453
Table 2
Adverse effects of misoprostol
Misoprostol,
mg/route
Abdominal pain/uterine
cramping, %
Abnormal
vaginal bleeding, %
200 Vg
400 Vg
400 PO
800 Vg
1000 Vg
400 PO
vs 400 Vga
32–63
36–79
6–65
100
7–12
25.6 (2/39)
vs 36.8 (1/38)
19–30
2–63
5–47
100
8–21
5.1 (10/39)
vs 2.6 (14/38)
Fever/shivering, %
Nausea, %
Diarrhea, %
Fatigue, %
Dizziness, %
3–11
7–17
0–3
43
0–3
NA
4–10
2–10
0–40
NA
0–9
5.1 (2/39)
vs 2.6 (1/38)
3–6
4–7
0–33
2
0–3
2.6(1/39)
vs 5.2 (2/38)
0–20
2–16
NA
NA
0–3
NA
0–10
7
0–20
NA
NA
NA
NA 5 not applicable; PO 5 oral administration; Vg 5 vaginal administration.
Comparison between 400 mg of vaginal and oral misoprostol 10–12 hours before operative hysteroscopy [40].
a
and more uterine cramping and pain associated with the procedure. No other cervical effects were noted [14].
In conclusion, with only 1 study to date, it seems that more
evidence is needed to support this application.
In conclusion, more studies are needed to establish the
benefits of misoprostol when used in myomectomy procedures before routine use of this application is recommended.
Adverse Effects
Misoprostol in IUD Insertion
The difficulty of insertion of IUDs arises in part from
a constricted cervix, especially in nulliparous women. Cervical priming using misoprostol might help resolve this problem; however, to our knowledge, only 1 study has
examined this possible treatment, and found that insertion
of a copper IUD in women treated with 400 mg of sublingual
misoprostol 1 hour before the procedure was judged to be
easier than in nontreated women. However, shivering and
diarrhea were more frequent adverse effects [62].
In conclusion, it seems that misoprostol may be an effective way to ease IUD insertion; however the dosage and
duration of misoprostol therapy in this role need further study
to minimize adverse effects.
Misoprostol in Myomectomy
Prostaglandins increase myometrial contractions and lead
to reduction in myometrial hemorrhage [63]. Misoprostol,
a PGE1 analogue, causes decreased uterine artery blood
flow when used in early pregnancy [64]. Celik and Sapmaz
[15] demonstrated that a single dose of 400 mg of vaginal misoprostol significantly reduced blood loss, operative time,
and the need for postoperative blood transfusion in myomectomy procedures. This use of misoprostol as an effective
method to decrease blood loss during myomectomy is also
noted in the Cochrane database [65]; however, because of
the small sample size in the Cochrane reference, only 13
women in the study group and 12 in the control group,
more data are needed to validate this outcome.
There has been concern about the variation of prostanoid
receptors present in the myometrium that may be related to
the phase of the menstrual cycle [66]. However, a later retrospective analysis from Celik [15] found no significant differences between women who were in the follicular phase or the
luteal phase of the cycle.
Many reports have found that the severity of adverse
symptoms (Table 2) after using misoprostol vary considerably [5,11–15,21,22,25,32–35,38,40,45,46,49,50] and are
often not correlated with dosage, interval of use, or route of
administration. To our knowledge, only 1 trial assessed the
efficacy of oral and vaginal administration using a similar
dose, 400 mg, before hysteroscopy [40]. Although the study
included only a limited sample, they reported no significant
differences insofar as adverse effects between the 2 regimens.
Insofar as the use of 400 mg of vaginal misoprostol that 1
report recommends before hysteroscopy [67], another clinical trial using the same dosage was terminated before
completion of the study because of excessive bleeding in
the misoprostol group [68].
Abnormal vaginal bleeding, lower abdominal pain or uterine cramping, and fever or shivering are the major adverse
effects of misoprostol, with nausea, diarrhea, and dizziness
the more common minor adverse effects. Various reports
indicate that the vaginal route of administration leads to
more uterine cramping and abnormal vaginal bleeding compared with the oral route. One study found that the systemic
bioavailability of misoprostol acid 6 hours after vaginal
administration was greater than with oral administration;
however, the difference was not significant [19]. There are
no current data about concentrations of misoprostol acid in
the myometrial or endometrial tissue after use of misoprostol,
and this is an area in which further studies might be useful in
helping us to understand the association between various
routes and dosages of misoprostol and adverse effects.
In conclusion, appropriate use of misoprostol in each
patient should be considered individually.
Conclusion
There is a broad spectrum of misoprostol use nowadays in
nonpregnant women, with mixed results. In premenopausal
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Journal of Minimally Invasive Gynecology, Vol 17, No 4, July/August 2010
women, misoprostol is capable of ripening the cervix before
hysteroscopy, although more research is required to identify
the optimal dosage and the timing and route of administration. Further studies in postmenopausal women or those receiving GnRH agonists are also needed to determine
whether misoprostol is effective for cervical ripening in
this population. Other potential applications exist; however,
more evidence is necessary before adopting the use of misoprostol in routine practice.
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Acknowledgements
We thank David F. Archer, MD, Professor of Obstetrics
and Gynecology and Director of CONRAD, and Thomas
D. Kimble, MD, at the Clinical Research Center at the Jones
Institute for Reproductive Medicine, Eastern Virginia Medical School, for valuable comments and editing suggestions.
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