ABSTRACT
Hemorrhoids are varicose veins of the rectum that are located in or near the anal
canal and are covered by mucosa. They can occur at any age, are generally
symptomless, and affect both sexes equally. Hemorrhoids are a common complaint
among younger women and are more likely to occur during pregnancy and the
menstrual cycle. In this article, we discuss the many approaches in the
treatment of hemorrhoids. Laxatives, stool softeners, and fiber supplements are
all considered safe for use by pregnant women. Moderate use of laxatives is also
acceptable. Since there is a lack of sufficient evidence to support the safety
and efficiency of topical medicines or oral phlebotomies during pregnancy, these
treatments must to be utilized with an increased degree of extreme caution. In
the case that considerable bleeding occurs, anal packing may be a straight
forward and helpful operation to implement. A hemorhoidectomy is the treatment
option for hemorrhoids that have become strangulated, badly thrombosed, or have
bleeding that cannot be controlled.
One of the most common disorders that can affect the anorectum is hemorrhoidal
disease. Anal bleeding, the sense of a prolapsing lesion, anal pain, anal
irritation, and anal soiling are not symptoms that are unique to hemorrhoidal
disease; however, these symptoms can occasionally be helpful in distinguishing
hemorrhoidal disease from other disorders [1,2]. In actual clinical practice,
classification of hemorrhoids was done based on the extent of internal hemorrhoidal
tissue prolapse, and treatment was outlined in accordance with classical
classification [3]. According to some
findings, classification systems that take into account many symptoms at once are
more practical [4,5]. The treatment for hemorrhoid was determined according to the
severity of the symptoms, which might range from conservative management to
intervention or surgical treatment [6–9]. Nevertheless, the
therapy of hemorrhoidal disease in unusual conditions is considerably more
challenging.
Hemorrhoidal disease is often symptomatic and bothersome for pregnant women. It
affects 25–35 percent of pregnant women [10], primarily presents in the third trimester, and can be internal or
external. There is a rise in blood volume (between 40% and 50% of the volume before
pregnancy). During pregnancy, there is an increase in cardiac output and
utero-placental blood flow, as well as an increase in the inflow and intravenous
pressure in the pelvic veins [11,12]. T These mechanisms result in increased
blood flow in collateral circulation veins (vulvar, rectal, and lumbar), which
increases the likelihood of developing hemorrhoids. The pelvic veins are compressed
during pregnancy due to the enlarged uterus [13]. In the first trimester of pregnancy, an increase in venous pressure
mixed with hormonal changes causes venous relaxation. Several mediators were
associated with these alterations. Estrogens are responsible for mesenchymal
release, but progesterone has a myolytic action across the body. These effects on
the vein system result in a tissue vascular dislocation (estrogen) and a decrease in
venous tone (progesterone) [13,14].
As a result of altered venous drainage through the hemorrhoid plexus, some
circumstances (such as constipation and prolonged exertion) may contribute to the
development of hemorrhoids by increasing intra-abdominal pressure [15]. Some dietary and lifestyle factors,
including as a diet low in fiber, spicy foods, and alcohol consumption, may
contribute to the development of hemorrhoids and the exacerbation of symptoms [16].
The most common manifestation of hemorrhoidal pathology is painless rectal bleeding
during feces, with or without anal tissue protrusion. Anal pain may be experienced
by patients with complex hemorrhoids, such as external hemorrhoids with thrombosis
or internal imprisoned hemorrhoids. On clinical examination, a nodule at the level
of the anal margin may be identified. It is uncommon for patients with simple
hemorrhoids to experience anal pain. Anal pain with hemorrhoids is more likely to be
caused by an anal fissure or an anal abscess [17].
The purpose of hemorrhoid treatment in pregnant women is to control the symptoms,
which typically disappear on their own during the postpartum period, and to protect
the perineal region, which is susceptible to stress during vaginal delivery. Except
in cases of acute thrombosis, a conservative approach is always suggested. If
possible, surgical procedures should be delayed until a few weeks after delivery. It
would be advantageous to avoid potential complications associated with
hemorrhoidectomy [18,19].
The consumption of fiber and fluids positively affects costipation, which is one of
the elements that contribute to the development of uterine fibroids during
pregnancy. Constipation is a risk factor for long-term pelvic organ prolapse when
combined with changes in anal sphincter pressure [20,21]. It is important to
consume fresh fruits and vegetables on a regular basis [22]. In a study of 40 pregnant women in their third trimester,
those who consumed 10 grams of fiber in the form of biscuits or wheat bran had
significantly greater digestive motility than the control group [23].
Moderate physical activity increases intestinal motility and promotes anorectal
coordination, and should be included among the prenatal hygiene interventions.The
usage of Psyllium in the treatment of constipation has been linked to enhanced
intestinal transit and intestinal motility, as well as the generation of soft,
highly-lubricated stool [24].
Osmotic laxatives contain ions or molecules that are not reabsorbable and that hold
water in the intestinal lumen. Polyethylene glycol and lactulose are the most widely
utilized. According to the meta-analysis, polyethylene glycol is more efficient than
lactulose in terms of stool frequency and consistency, with fewer adverse effects;
osmotic laxatives should be considered the first choice [25]. In addition, the favorable safety and tolerability profile
enables their use in unique circumstances, such as pregnancy. The safety of
stimulant laxatives during pregnancy is not currently recommended because there are
insufficient evidences of their safety profiles.Sitz-baths diminish the tone of the
internal sphincter, alleviate venous congestion, edema, and inflammation, and
provide excellent symptomatic control for inflamed hemorrhoids [26]. A study of two groups of patients with
acute anal pain due to hemorrhagic disease or anal fissure (24 patients in total, 12
for each group) who had used cold water [group 1, 10.8°C (range 5–13)]
and hot water [group 2, 38.5°C (range 20–40)] did not reveal any
differences in the clinical course of the disease, despite a reduction in painful
symptoms with the use of hot water [27].
Because ice has a local anesthetic effect, applying it directly to an injury can
make it feel less painful [28]. The analgesic
effect of cold was achieved by decreasing cellular metabolism and sensory nerve
transmission, which led to sphincter relaxation. Additionally, local
vasoconstriction helped diminish edema and swelling of the tissue, which contributed
to the analgesic effect of cold.
The goal of the medical treatment for hemorrhoids that occur during pregnancy is to
alleviate the symptoms, however the therapeutic options are restricted.
Anti-inflammatory medications are frequently taken in order to acquire a rapid
regression of the symptoms; nevertheless, the usage of these medications is
associated with the risk of developing problems. Corticosteroids and non-steroidal
anti-inflammatory medications are the most often used anti-inflammatory drugs,
however they cannot be used during or after nursing. There are insufficient
scientific studies to demonstrate the safety and efficacy of steroidal
anti-inflammatory medicines, whether they are administered orally, topically, or
with suppositories [10]. Long-term topical
steroid usage is connected with the development of allergic reactions and
sensitization. Multiple investigations have indicated that the teratogenic effect of
oral corticosteroids is dose-dependent, and four case-control studies have
demonstrated an association between corticosteroids use and the development of cleft
palate [29].
Inhaled corticosteroids were observed to be connected with a modest increase in the
risk of spontaneous abortion during pregnancy. On the other hand, oral
corticosteroids were not related to an increase in the risk of congenital
abnormalities [30]. Because breastfeeding
makes it unsafe to use nonsteroidal anti-inflammatory drugs, it was recommended that
pregnant women with thrombotic hemorrhoids and significant edema before and after
delivery use corticosteroids at a dose of 40 mg per day for three to five days.
Although betamethasone is the most often used corticosteroid in clinical practice,
dexamethasone exhibited similar efficacy [31]. However, the prenatal exposure to dexamethasone was observed to
increase the chance of neurological changes when compared to betamethasone and
placebo [32].
Paracetamol, also known as acetaminophen and N-acetyl-p-aminophenol, can be
recommended to alleviate uncomfortable sensations at the typical dose; nevertheless,
recent research has indicated its relation with fetal development problems [33]. It is not recommended to use codeine while
breastfeeding and is only safe to take during the first and second trimesters of
pregnancy for a limited amount of time. Treatment with tramadol is only permitted in
the second trimester of pregnancy [34]. The
application of topical anesthetics such as benzocaine, dibucaine, and pramoxine
after each defecation can alleviate anal itching and discomfort, with possible
sensitization following prolonged use [22].
For the treatment of hemorrhagic diseases, phlebotonic drugs are commonly
prescribed.Phlebotonics function as antioxidants, exert a protective effect against
pro-inflammatory mediators, and enhance venous tone and lymph drainage. Floavonoid
has been shown to be effective in the treatment of hemorrhoids illness in pregnant
women, and it has been shown to decrease symptoms such as bleeding, itching, and
recurrence of hemorrhoid [35]. Micronized
pure flavonoic fraction has demonstrated efficacy in lowering pain and bleeding in
patients with acute hemorrhoidal episodes, in addition to tolerability [36]. Rutosides belong to the family of
flavonoids, which are plant-derived natural compounds. These are recommended drugs
for treating chronic venous insufficiency. Although their mechanism of action is not
well understood, the phlebotonic effect (the action of boosting venous tone) may be
associated with an increase in lymphatic drainage (drawing of linfatic fluids), an
improvement in venous tone, and a decrease in capillary hyper permeability (the
passage of substances through the membrane of the smallest vessels). In patients
with pregnancy-related grade I–III hemorrhoids, rutoside, a flavonoic
glycoside, shown considerable improvement in pain alleviating, in comparison to
placebo [37]. The symptoms of nausea,
dizziness, gastrointestinal pain, vomiting, dry mouth, constipation, headache, and
fatigue were the ones that were reported as occurring the most frequently in
patients who experienced adverse reactions. Compared to placebo, there were no
significant differences in adverse reactions, fetal death, early delivery, or
congenital abnormalities. Nonetheless, several researches discovered a link between
Rutoside and congenital abnormality and advised against its use during the first
trimester of pregnancy [38,39]. There were no adverse effects recorded in
terms of issues with prenatal development, birth weight, or postnatal nutrition in
connection with the usage of 500 mg of Daflon [22]. It was recommended that micronized diamines (Daflon) be
administered at a dose of 1–2 g/day for short periods only, and not for
prolonged use [34]. Lacroix et al. [40] reported the first epidemiological data
about suspected veinotonic side effects in pregnant women. They discovered no higher
risk of unfavorable pregnancy outcomes in women exposed to veinotonics compared to
those who were not exposed.According to a double-blind, randomized, controlled
trial, weakened calcium, a phlebotonic medication with anti-haemodynamic action, is
helpful in treating the acute phase of hemorrhoids, with a marked reduction in
inflammation [41]. Dobesilated calcium
(calcium 2,5-dihydroxybenzenesulfonate) inhibits, dose-dependently, the production
of PGF1a, PGF2a, PGE2, and TXB2 [42]. Calcium
Dobesilate impacts blood pressure and, as a result, reduces the need for medication
and hospitalization in cases of mild to moderate midtrimester hypertension,
according to a pilot research [43]. There
have not been enough research done to determine the safety profile or the
teratogenicity of the weakened calcium when it is consumed during pregnancy.
The treatment of hemorroids during pregnancy should be conservative, consisting of
improving eating habits and using suppositories or ointments as necessary.
Sclerotherapy, which involves injecting sclerosing chemicals at the level of the
hemorrhagic plexus, is a controversial operation that can be performed during
pregnancy. In the majority of instances, hemorrhoids disappear on their own within
two months of delivery, along with the regression of risk factors that contributed
to their development [44,45]. In the event of severe bleeding and pain
that does not respond to any of the available analgesics, invasive procedures can be
considered medically necessary during pregnancy. Thrombosis of the caudal hemorrhoid
cushion is what causes hemorrhoids to protrude along the anal border and the anal
canal. This condition is known as hemorrhoids thrombosis. Pain that comes on
suddenly and swelling at the level of the anal edge are both symptoms of hemorrhoid
thrombosis. The diagnosis can be easily confirmed by an examination of the perianal
region. Surgery is typically not indicated for patients who have inadequate symptoms
in their condition. The aim of the treatment is to lessen the patient's level
of discomfort by way of a systemic anti-inflammatory approach utilizing
non-steroidal anti-inflammatory medicines. Ibuprofen and Diclofenac can be taken
throughout pregnancy up until the 30th week of the pregnancy. It was previously
thought that paracetamol could be taken throughout the entirety of a woman's
pregnancy; however, growing evidence from both experimental and epidemiological
research suggests that prenatal exposure to paracetamol may alter fetal development,
which may in turn increase the risk of certain neurodevelopmental, reproductive, and
urogenital disorders. Caution is therefore required when using this medication
during pregnancy [33]. Anesthetic ointments,
such as Procain, Bupivacin, Lidovain, and Mepivacain, as well as local cooling, may
be used in conjunction with the systemic treatment. With this conservative
treatment, the pain should go away in a few days, and although the nodule will
remain, it should go away on its own in two to four weeks [46]. Necrosis of the vascular wall and skin can, in extremely
rare instances, be linked with spontaneous resolution of the thrombus, which in turn
leads to relief of the symptoms. In urgent circumstances, due to the severe pain and
the presence of a large thrombus, local anesthesia is used for surgical treatment,
which involves the complete excision of the whole thrombosed hemorrhoid. Some have
reported that metronidazole would be effective in the management of
post-hemorrhoidectomy pain. a thrombus is a collection of blood cells that can block
blood flow through a blood vessel [47].
Because there is a risk of the thrombus forming again, surgical procedures such as
incision and drainage are not advised [48,49].
The most common kind of anorectal disease that occurs during pregnancy is
hemorrhoids, particularly in the third trimester [50]. At the beginning of treatment for hemorrhoids that occur during
pregnancy, a conservative approach is utilized. The most significant risk factor,
which is also present in the general population, is refractory constipation, which
is often accompanied by the possibility of traumatic vaginal birth. In order to
limit the incidence of symptomatic hemorrhoids, it is crucial to avoid constipation
during pregnancy, particularly after childbirth.Short-term relief of symptoms may be
achieved through the use of local interventions such as sitz baths, ice, or
ointments containing anesthetics, phlebotonics, or glucocorticoids, either alone or
in combination. Surgery for an incurable sickness ought to be put off until the
fetus is no longer in danger, or even better, until after the baby has been born.
Excision is necessary as soon as possible for external hemorrhoids that have
developed acute strangulation thrombosis.
References
1. Ng KS, Holzgang M, Young C. Still a case of “no pain, no gain”? An updated and
critical review of the pathogenesis, diagnosis, and management options for
hemorrhoids in 2020. Ann Coloproctol. 2020; 36(3):133–147. DOI: 10.3393/ac.2020.05.04. PMID: 32674545. PMCID: PMC7392573.
2. Pham BV, Kang JH, Phan HH, Cho MS, Kim NK. Malignant melanoma of anorectum: two case reports. Ann Coloproctol. 2021; 37(1):65–70. DOI: 10.3393/ac.2020.01.07.1. PMID: 33730798. PMCID: PMC7989557.
3. Goligher JC. Haemorrhoids or piles. In. Goligher JC, Duthie HL, Nixon HH, editors. editors. Surgery of the anus, rectum and colon. 4th ed. London: Baillière Tindall;1980. p. 96.
4. Sobrado Júnior CW, de Almeida Obregon C, da Silva e Sousa Júnior AH, Sobrado LF, Nahas SC, Cecconello I. A new classification for hemorrhoidal disease: the creation of
the “BPRST” staging and its application in clinical
practice. Ann Coloproctol. 2020; 36(4):249–255. DOI: 10.3393/ac.2020.02.06. PMID: 32674550. PMCID: PMC7508483.
5. Fathallah N, Beaussier H, Chatellier G, Meyer J, Sapoval M, Moussa N, et al. Proposal for a new score: hemorrhoidal bleeding
score. Ann Coloproctol. 2021; 37(5):311–317. DOI: 10.3393/ac.2020.08.19. PMID: 32972102. PMCID: PMC8566148.
6. Jeong H. The effort to reduce vasovagal reaction and abdominal pain during
stapled hemorrhoidopexy. Ann Coloproctol. 2020; 36(5):291–292. DOI: 10.3393/ac.2020.10.13. PMID: 33207111. PMCID: PMC7714375.
7. Yano T. Is there a relationship between stool consistency and pain at
first defecation after limited half hemorrhoidectomy? A pilot
study. Ann Coloproctol. 2021; 37(5):306–310. DOI: 10.3393/ac.2020.08.10. PMID: 32972107. PMCID: PMC8566150.
8. Bhatti MI, Sajid MS, Baig MK. Milligan–Morgan (open) versus Ferguson haemorrhoidectomy
(closed): a systematic review and meta-analysis of published randomized,
controlled trials. World J Surg. 2016; 40(6):1509–1519. DOI: 10.1007/s00268-016-3419-z. PMID: 26813541.
9. Brown SR. Haemorrhoids: an update on management. Ther Adv Chronic Dis. 2017; 8(10):141–147. DOI: 10.1177/2040622317713957. PMID: 28989595. PMCID: PMC5624348.
10. Altomare DF, Giannini I. Pharmacological treatment of hemorrhoids: a narrative
review. Expert Opin Pharmacother. 2013; 14(17):2343–2349. DOI: 10.1517/14656566.2013.836181. PMID: 24024752.
11. Hills DL, Firth BG, Wi ni ford, Willer son IT. Pregnancy and cardiovascular abnormalities of clinical problems in
cardiology. ABE;Milan: 1990. p. 917–927.
12. Struckmann JR, Meiland H, Bagi P, Juul-Jørgensen B. Venous muscle pump function during pregnancy. Assessment by
ambulatory strain-gauge plethysmography. Acta Obstet Gynecol Scand. 1990; 69(3):209–215. DOI: 10.3109/00016349009028682. PMID: 2220341.
13. Williams JW, Cunningham FG, Mc Donald PC, Gant NF. Williams obstetrics. 18th ed. Appleton & Lange;Nor walk: 1989. p. 129–168.
14. Cruikshank DP. Cardiovascular, pulmonary, renal and hematologic disease in
pregnancy. In. Scott JR, Disain PJ, Hammond CB, Spellacy WN, editors. editors. Danforth’s obstetrics and gynecology. 6th ed. Philadelphia: Lippincott;1990. p. 433–459.
15. Loder PB, Kamm MA, Nicholls RJ, Phillips RKS. Haemorrhoids: pathology, pathophysiology and
aetiology. Br J Surg. 1994; 81:946–954. DOI: 10.1002/bjs.1800810707. PMID: 7922085.
16. Pigot F, Siproudhis L, Allaert FA. Risk factors associated with hemorrhoidal symptoms in specialized
consultation. Gastroentérol Clin Biol. 2005; 29(12):1270–1274. DOI: 10.1016/S0399-8320(05)82220-1.
17. Lohsiriwat V. Hemorrhoids: from basic pathophysiology to clinical
management. World J Gastroenterol. 2012; 18(17):2009–2017. DOI: 10.3748/wjg.v18.i17.2009. PMID: 22563187. PMCID: PMC3342598.
18. Assaraf J, Lambrescak E, Lefèvre JH, de Parades V, Bourguignon J, Etienney I, et al. Increased long-term risk of anal fistula after proctologic
surgery: a case-control study. Ann Coloproctol. 2021; 37(2):90–93. DOI: 10.3393/ac.2019.06.18. PMID: 32054251. PMCID: PMC8134930.
19. Cho KJ, Hwang DY, Lee HJ, Hyun KH, Kim TJ, Park DH. Prospective comparative analysis of the incidence of vasovagal
reaction and the effect of rectal submucosal lidocaine injection in stapled
hemorrhoidopexy: a randomized controlled trial. Ann Coloproctol. 2020; 36(5):344–348. DOI: 10.3393/ac.2020.02.12. PMID: 32178498. PMCID: PMC7714374.
20. Tsunoda A, Takahashi T, Sato K, Kusanagi H. Factors predicting the presence of concomitant enterocele and
rectocele in female patients with external rectal prolapse. Ann Coloproctol. 2021; 37(4):218–224. DOI: 10.3393/ac.2020.07.16. PMID: 33445838. PMCID: PMC8391036.
21. Büyükaşık S, Abdussamet Bozkurt M, Kapan S, Alis H. Analyzing the role of anal sphincter pressure in rectocele
formation. Ann Coloproctol. 2020; 36(5):330–334. DOI: 10.3393/ac.2019.09.15. PMID: 32178503. PMCID: PMC7714383.
22. Avsar AF, Keskin HL. Haemorrhoids during pregnancy. J Obstet Gynaecol. 2010; 30(3):231–237. DOI: 10.3109/01443610903439242. PMID: 20373920.
23. Jewell DJ. Interventions for treating constipation in
pregnancy. Cochrane Database Syst Rev. 2015; (9):CD011448. DOI: 10.1002/14651858.CD011448.pub2. PMID: 26342714. PMCID: PMC8958874.
24. Singh B. Psyllium as therapeutic and drug delivery agent. Int J Pharm. 2007; 334(1–2):1–14. DOI: 10.1016/j.ijpharm.2007.01.028. PMID: 17329047.
25. Lee-Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus polyethylene glycol for chronic
constipation. Cochrane Database Syst Rev. 2010; (7):CD007570. DOI: 10.1002/14651858.CD007570.pub2. PMID: 20614462.
26. Shafik A. Role of warm-water bath in anorectal conditions. J Clin Gastroenterol. 1993; 16(4):304–308. DOI: 10.1097/00004836-199306000-00007. PMID: 8331263.
27. Maestre Y, Parés D, Salvans S, Ibáñez-Zafón I, Nve E, Pons MJ, et al. Cold or hot sitz baths in the emergency treatment of acute anal
pain due to anorectal disease? Results of a randomised clinical
trial. Cir Esp. 2010; 88(2):97–102. DOI: 10.1016/j.ciresp.2010.04.007. PMID: 20580349.
28. Ashaal YE, Chandran VP, Siddiqui MN, Sim AJ. Local anal hypothermia with a frozen finger: a treatment for
acute painful prolapsed piles. Br J Surg. 1998; 85(4):520. DOI: 10.1046/j.1365-2168.1998.00647.x. PMID: 9607538.
29. Lim SS, Yu CW, Aw LD. Comparing topical hydrocortisone cream with Hai's perianal
support in managing symptomatic hemorrhoids in pregnancy: a preliminary
trial. J Obstet Gynaecol Res. 2015; 41(2):238–247. DOI: 10.1111/jog.12523. PMID: 25256125.
30. Bjørn AMB, Ehrenstein V, Nohr EA, Nørgaard M. Use of inhaled and oral corticosteroids in pregnancy and the risk
of malformations or miscarriage. Basic Clin Pharmacol Toxicol. 2015; 116(4):308–314. DOI: 10.1111/bcpt.12367. PMID: 25515299.
31. Elimian A, Garry D, Figueroa R, Spitzer A, Wiencek V, Quirk JG. Antenatal betamethasone compared with dexamethasone (betacode
trial): a randomized controlled trial. Obstet Gynecol. 2007; 110(1):26–30. DOI: 10.1097/01.AOG.0000268281.36788.81. PMID: 17601892.
32. Lee BH, Stoll BJ, McDonald SA, Higgins RD. Neurodevelopmental outcomes of extremely low birth weight infants
exposed prenatally to dexamethasone versus betamethasone. Pediatrics. 2008; 121(2):289–296. DOI: 10.1542/peds.2007-1103. PMID: 18245420.
33. Bauer AZ, Swan SH, Kriebel D, Liew Z, Taylor HS, Bornehag CG, et al. Paracetamol use during pregnancy: a call for precautionary
action. Nat Rev Endocrinol. 2021; 17(12):757–766. DOI: 10.1038/s41574-021-00553-7. PMID: 34556849. PMCID: PMC8580820.
34. Abramowitz L, Benabderrhamane D, Philip J, Pospait D, Bonin N, Merrouche M. Pathologie hémorroïdaire de la
parturiente. Presse Med. 2011; 40(10):955–959. DOI: 10.1016/j.lpm.2011.06.015. PMID: 21840677.
35. Alonso-Coello P, Zhou Q, Martinez-Zapata MJ, Mills E, Heels-Ansdell D, Johanson JF, et al. Meta-analysis of flavonoids for the treatment of
haemorrhoids. Br J Surg. 2006; 93(8):909–920. DOI: 10.1002/bjs.5378. PMID: 16736537.
36. Jiang ZM, Cao JD. The impact of micronized purified flavonoid fraction on the
treatment of acute haemorrhoidal episodes. Curr Med Res Opin. 2006; 22(6):1141–1147. DOI: 10.1185/030079906X104803. PMID: 16846547.
37. Alonso P, Johanson J, Lopez-Yarto M, Martinez MJ. Phlebotonics for haemorrhoids. Cochrane Database Syst Rev. 2003; (1):004322. DOI: 10.1002/14651858.CD004322.
38. Vazquez JC. Constipation, haemorrhoids, and heartburn in
pregnancy. BMJ Clin Evid. 2010; 2010:1411.
39. Kubicsek T, Kazy Z, Czeizel AE. Teratogenic potential of tribenoside, a drug for the treatment of
haemorrhoids and varicose veins: a population-based case–control
study'. Reprod Toxicol. 2011; 31(4):464–469. DOI: 10.1016/j.reprotox.2010.12.001. PMID: 21182931.
40. Lacroix I, Beau AB, Hurault-Delarue C, Bouilhac C, Petiot D, Vayssière C, et al. First epidemiological data for venotonics in pregnancy from the
EFEMERIS database. Phlebology. 2016; 31(5):344–348. DOI: 10.1177/0268355515589679. PMID: 26060062.
41. Menteş BB, Görgül A, Tatlicioğlu E, Ayoğlu F, Ünal S. Efficacy of calcium dobesilate in treating acute attacks of
hemorrhoidal disease. Dis Colon Rectum. 2001; 44(10):1489–1495. DOI: 10.1007/BF02234604. PMID: 11598479.
42. Falkay G, Kovács L. Calcium dobesilate (doxium) as a prostaglandin synthetase
inhibitor in pregnant human myometrium in vitro. Experientia. 1984; 40(2):190–191. DOI: 10.1007/BF01963593. PMID: 6421615.
43. Tamás P, Csermely T, Ertl T, Vizer M, Szabó I, Prievara FT. Calcium dobesilate lowers the blood pressure in mild to moderate
midtrimester hypertension: a pilot study. Gynecol Obstet Invest. 1999; 47(3):210–213. DOI: 10.1159/000010080. PMID: 10087420.
44. Kersting S, Loch H. Coloproctological problems in pregnancy and
postpartum. Chir Mag. 2007; 29:22–25.
45. Brühl W, Wienert V, Herold A. Hämorrhoiden. Current proctology. Bremen: Uni-med Verlag;2005. p. 56–71.
46. Bussen S, Herold A, Schmittner M, Krammer H, Bussen D. Coloproctological diseases in pregnancy and the postpartum
period. Geburtsh Frauenheilkd. 2008; (11):68:1–5. DOI: 10.1055/s-2008-1039050.
47. Di Re A, Toh JWT, Iredell J, Ctercteko G. Metronidazole in the management of post-open haemorrhoidectomy
pain: systematic review. Ann Coloproctol. 2020; 36(1):5–11. DOI: 10.3393/ac.2020.01.08. PMID: 32146782. PMCID: PMC7069672.
48. Herold A. Analvenenthrombose. In. Brühl W, Wienert V, Herold A. editors. Current proctology. Bremen: Uni-med Verlag;2005. p. 72–76.
49. Forner DM, Vestweber KH, Lampe B. Proctological diseases in gynecological practice. Frauenarzt. 2006; 47:102–106.
50. Gojnic M, Dugalic V, Papic M, Vidaković S, Milićević S, Pervulov M. The significance of detailed examination of hemorrhoids during
pregnancy. Clin Exp Obstet Gynecol. 2005; 32(3):183–184.