Therapeutic approaches to Lysosomal Storage Disorders: the ...
Current therapeutic approaches to managing dysmenorrhoea · Current therapeutic approaches to...
4
PRESCRIBING IN PRACTICE n Prescriber 19 June 2013 z 31 prescriber.co.uk D ysmenorrhoea is a common condi- tion defined as the occurrence of monthly painful cramps at the time of menstruation that are distressing and require some form of treatment to allevi- ate the pain and to allow continuation of daily activities. Dysmenorrhoea can be either primary or secondary. Primary dysmenorrhoea Primary dysmenorrhoea refers to painful periods that are not associated with iden- tifiable pelvic pathology. It is commoner in the years after menarche peaking at 20–24 years of age and decreasing there- after (see Table 1). It occurs in up to 40– 50 per cent of young women, with severe forms limiting activity and causing missed school days in 15 per cent. 1 Primary dysmenorrhoea usually starts within 6–12 months of menarche, once ovulatory cycles are established. Present ation beyond a year after menar- che should give rise to suspicion of sec- ondary dysmenorrhoea. Typically, pains are cramping and spasmodic, coming on a few hours after the onset of flow and peaking 24–36 hours into the period. They rarely last more than two or three days and can be accompanied by backache, nausea, vom- iting and diarrhoea. In keeping with the definition of pri- mary dysmenorrhoea, abdominal and pelvic examinations are normal. Pathophysiology The most important cause of primary dys- menorrhoea is thought to be excessive secretion of prostanoids that induce uterine contractions, reducing uterine blood flow leading to uterine hypoxia and pain. The symptoms accompanying primary dysmen- orrhoea, ie nausea, vomiting and diarrhoea, are typical of prostaglandin adverse effects. Secondary dysmenorrhoea In contrast to primary dysmenorrhoea, sec- ondary dysmenorrhoea is a consequence of the presence of pelvic pathology. The typical age of patients is the third or fourth decade of life and it may be associated with other symptoms such as dyspareunia, Current therapeutic approaches to managing dysmenorrhoea Dimitrios Mavrelos MD, MRCOG and Ertan Saridogan PhD, MD, FRCOG Dysmenorrhoea is a com- mon condition associated with potentially distressing cramps. The authors discuss the features that distinguish primary and secondary dys- menorrhoea and assess the currently available treat- ment options. SPL
Transcript of Current therapeutic approaches to managing dysmenorrhoea · Current therapeutic approaches to...
PRESCRIBING IN PRACTICE n
Prescriber 19 June 2013 z 31prescriber.co.uk
Dysmenorrhoea is a common condi-tion defined as the occurrence of
monthly painful cramps at the time ofmenstruation that are distressing andrequire some form of treatment to allevi-ate the pain and to allow continuation ofdaily activities. Dysmenorrhoea can be either primary
or secondary.
Primary dysmenorrhoeaPrimary dysmenorrhoea refers to painfulperiods that are not associated with iden-tifiable pelvic pathology. It is commonerin the years after menarche peaking at20–24 years of age and decreasing there-after (see Table 1). It occurs in up to 40–50 per cent of young women, with severeforms limiting activity and causing missedschool days in 15 per cent.1
Primary dysmenorrhoea usuallystarts within 6–12 months of menarche,once ovulatory cycles are established.Present ation beyond a year after menar-che should give rise to suspicion of sec-ondary dysmenorrhoea. Typically, pains are cramping and
spasmodic, coming on a few hours afterthe onset of flow and peaking 24–36hours into the period. They rarely lastmore than two or three days and can beaccompanied by backache, nausea, vom-iting and diarrhoea.
In keeping with the definition of pri-mary dysmenorrhoea, abdominal andpelvic examinations are normal.
Pathophysiology The most important cause of primary dys-menorrhoea is thought to be excessivesecretion of prostanoids that induce uterinecontractions, reducing uterine blood flowleading to uterine hypoxia and pain. Thesymptoms accompanying primary dysmen-orrhoea, ienausea, vomiting and diarrhoea,are typical of prostaglandin adverse effects.
Secondary dysmenorrhoeaIn contrast to primary dysmenorrhoea, sec-ondary dysmenorrhoea is a consequenceof the presence of pelvic pathology. Thetypical age of patients is the third or fourthdecade of life and it may be associatedwith other symptoms such as dyspareunia,
Current therapeutic approachesto managing dysmenorrhoea Dimitrios Mavrelos MD, MRCOG and Ertan Saridogan PhD, MD, FRCOG
Dysmenorrhoea is a com-mon condition associatedwith potentially distressingcramps. The authors discussthe features that distinguishprimary and secondary dys-menorrhoea and assess thecurrently available treat-ment options.
SPL
dyschezia and disturbances of the men-strual cycle (see Table 1). The commonest pathophysiological
process involved is endometriosis.Adenomyosis is often found at the sametime as endometriosis and can compoundpain during menstruation.2
Dysmenorrhoea can also be secondaryto previous pelvic infection that led to adhe-sions that envelop the ovaries and/orocclude the Fallopian tubes causinghydrosalpinges. Fibroids cause uterineenlargement and are commonly associ-ated with menorrhagia that may also causedysmenorrhoea. Structural abnormalitiesof the endometrium such as polyps giverise to cycle disturbances and can beaccompanied by pain during menstruation.
Rare causes of dysmenorrhoeainclude uterine anomalies (eg unicornuateuterus with a noncommunicating rudimen-tary uterine cornu) or cervical stenosis.
Diagnostic approach to dysmenorrhoeaThe starting point in distinguishing betweenprimary and secondary dysmenorrhoea isthe history. Primary dysmenorrhoea affectsa younger age group of women and startssoon after the onset of menstruation. Thepain is confined to the period and rarelylasts longer than two to three days. In contrast secondary dysmenorrhoea
usually affects older women with painstarting before the onset of bleeding andcontinuing throughout. Secondary dys-
menorrhoea is associated with secondaryeffects of the underlying pathology suchas dyspareunia and dyschezia. While in primary dysmenorrhoea
examination will be normal, secondarydysmenorrhoea is by definition associatedwith significant clinical findings. Pelvicexamination in women with endometriosismay reveal a fixed retroverted uterus dueto occlusion of the pouch of Douglasand/or the presence of thickeneduterosacral ligaments or rectovaginal sep-tum due to endometriotic nodules. The uterus will be enlarged in women
with fibroids, and pelvic tenderness maybe elicited by gentle palpation in womenwith pelvic inflammatory disease. Pelvicexamination may be inappropriate in
n PRESCRIBING IN PRACTICE l Dysmenorrhoea
32 z Prescriber 19 June 2013 prescriber.co.uk
Table 1. Distinguishing features of primary and secondary dysmenorrhoea
Primary dysmenorrhoea Secondary dysmenorrhoea
Pathophysiology no underlying gynaecological pathology pain manifestation of underlying gynaecologicalpathology
HistoryAge 16–25 years 30–45 years
Onset menarche after menarche
Duration 8–72 hours during menses prior to +/- throughout menstrual cycle; variable number of days
Nature cramping pelvic pain, with or without nausea variable number of days; noncyclical and cyclicaland vomiting, which commences with the start episodesof menstrual flow; the pain may radiate to thelower back or upper legs
Co-morbidity no other gynaecological, renal tract or co-existent gynaecological symptoms, eg heavygastrointestinal symptoms periods, dyspareunia, vaginal discharge,
intermenstrual bleeding, postcoital bleeding,chronic pelvic pain; possible bowel and urologicalsymptoms
Responds to yes yes, but may require further treatmentNSAIDs or COCs
Clinical normal pelvis fixed retroverted uterus, thickened uterosacral examination ligaments, endometriotic nodules on vaginal
examination, enlarged tender uterus, adnexal masses
Specialist normal pelvic ultrasound pelvic ultrasound may show adenomyosis or investigations no evidence of PID uterine fibroids, ovarian endometriosis, evidence
of PID on genital tract swabs
teenagers and a transabdominal scanmay be an alternative.Pelvic ultrasound is the starting point
in the investigation of dysmenorrhoea andrecent advances allow the identificationof endometriosis, adenomyosis, uterinefibroids and congenital uterine anomalies,all of which are associated with dysmen-orrhoea.2,3
First- and second-line medicaltreatmentNSAIDsA large number of NSAIDs have been com-pared to placebo in terms of their effec-tiveness in relieving menstrual pain. Theyhave all been found to be effective treat-ments for dysmenorrhoea except aspirin.4
NSAIDs have also been shown to reduceinterference with daily activities andschool absenteeism when compared toplacebo in dysmenorrhoea. The evidence in terms of their relative
effectiveness in symptom relief is limitedso NSAID choice will depend on their side-effect profile and clinician familiarity. NSAIDs are associated with significant
side-effects, although the three-day regi-men used when treating primary dysmen-orrhoea is unlikely to bring these about.In the pooled results of placebo-controlledrandomised trials, gastro intestinal side-effects were the commonest reported. More recently, COX-2 inhibitors had
been heralded as a potentially more effec-tive treatment for dysmenorrhoea. However,those that have not been withdrawn due tosafety concerns have not been shown to besuperior to COX-1 inhibitors.
Oral contraceptivesSynthetic hormones, and more recentlynatural oestrogen, that suppress ovula-tion improve the symptoms of dysmenor-rhoea. Inhibition of ovulation and reducedvolume of endometrium at the time ofmenstruation reduce the amount ofprostaglandins produced thereby relievingmenstrual cramps. In addition to makingperiods less painful, the combined oralcontraceptive can be taken continuouslythereby reducing the number of cycles thepatient goes through. Similarly injectableprogestogens can also be used to inducereversible amenorrhea although they areassociated with irregular bleeding.
Alternative delivery methods for com-bined oral contraception include transder-mal skin patches and vaginal rings, whichmay be more suitable to those for whomdaily pill taking is difficult. The ability of oral combined contra-
ceptives to relieve menstrual pain hasbeen borne out by placebo-controlled tri-als that demonstrate significant pain reliefwith all combined oral contraceptivescompared to placebo in women with pri-mary dysmenorrhoea.5
Intrauterine devicesThe levonorgestrel-releasing intrauterinesystem (Mirena) has been shown to beassociated with improved pain scores andreduced menstrual flow in women withadenomyosis and endometriosis. In con-trast the copper IUD may be associatedwith an increase in menstrual pain.6,7
Other pharmacological treatmentsAgents that bring about myometrial relax-ation can be used to relieve primary dys-
menorrhoea. However these agents arenot licensed for such use and thereforecaution is advised. Nitric oxide is effective for pain relief
when compared to placebo, but comparedto diclofenac sodium the GTN patch hasreduced efficacy with low tolerability.8,9
Similar results have been obtained withnifedipine, a calcium-channel blocker.
Nonpharmacological treatmentsA variety of nonpharmacological treat-ments for dysmenorrhoea have been sug-gested. There is limited evidence thathigh-frequency transcutaneous electricalnerve stimulation (TENS) is effective inreducing menstrual pain. A meta-analysis of randomised con-
trolled trials found that behaviour modifi-cation techniques, eg pain managementtraining and relaxation plus biofeedback,may help with pain but the evidence is lim-ited and the results not conclusive.10
The evidence regarding acupuncture,spine manipulation, fish oil and herbal
Dysmenorrhoea l PRESCRIBING IN PRACTICE n
Prescriber 19 June 2013 z 33prescriber.co.uk
Dysmenorrhoea
History and examination
No pelvic pathology suspected or detected
Requires contraception
COC
Relief No relief
Combined COC+ NSAID
No relief Refer to gynaecologist
Suspected secondarydysmenorrhoea
No significantpathology
Pelvic ultrasoundscan
Significantpathology
noyes
NSAID
Figure 1. Treatment pathway for women presenting with dysmenorrhoea in primary care
medicine is inconclusive due to poor-qual-ity data and therefore these cannot be rec-ommended.11
When to referThe detection of significant pelvic pathologythat is refractory to first- and second-linetreatment options should prompt referral tosecondary care where definitive, often sur-gical, treatment can be discussed forendometriosis, adenomyosis and fibroids. It is reported that 50–70 per cent of
teenagers who do not respond to medical
treatments with NSAIDs and the COC havepelvic endometriosis,12 and such patientswill benefit from specialist review.
References1. Dawood MY. Obstet Gynecol 2006;108(2):428–41.2. Naftalin J, et al. Human Reproduction2012;27(12):3432–9.3. Holland TK, et al. Ultrasound Obstet Gynecol2010;36(2):241–8. 4. Marjoribanks J, et al. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea.Cochrane database of systematic reviews
2010(1):CD001751. 5 Wong CL, et al. Oral contraceptive pill as treat-ment for primary dysmenorrhoea. Cochranedatabase of systematic reviews 2009(2):CD002120. 6. Kelekci S, et al. Contraception 2012;86(5):458–63. 7. Petta CA, et al. Eur J Obstet Gynecol ReprodBiol 2009;143(2):128–9. 8. Moya RA, et al. Int J Gynaecol Obstet2000;69(2):113–8. 9. Facchinetti F, et al. Gynecol Endocrinol2002;16(1):39–43.10. Proctor ML, et al. Behavioural interventionsfor primary and secondary dysmenorrhoea.Cochrane database of systematic reviews2007(3):CD002248. 11. Khan KS, et al. BMJ 2012;344:e3011.12. Stavroulis AI, et al. Eur J Obstet GynecolReprod Biol 2006;25(2):248–50.
Declaration of interestsNone to declare.
Dr Mavrelos is academic clinical lecturerand Dr Saridogan is consultant in repro-ductive medicine and minimal accesssurgery, Institute for Women’s Health,University College London Hospitals
n PRESCRIBING IN PRACTICE l Dysmenorrhoea
34 z Prescriber 19 June 2013 prescriber.co.uk
Resources
Royal College of Obstetricians and Gynaecologists. The college publishes a series ofleaflets and has a patient information section. www.rcog.org.uk.
National Association for Premenstrual Syndrome. A patient support group with anonline forum and frequently asked questions section. www.pms.org.uk.
Women’s Health Concern. An independent organisation providing advice and edu-cation regarding women’s health issues. www.womens-health-concern.org.
The Pelvic Pain Support Network. A patient support group including articles aimedat health professionals. www.pelvicpain.org.uk.
