Menstrual cycle disorders are a very frequent reason for consultation, from puberty to menopause. The pathophysiological mechanisms are multiple, requiring semiological analysis cycle disorder. Some setting reminders are needed (Box 1)
Box 1. Definitions
Amenorrhoea: it is defined by the lack of monthlies for more than three months. It is called primary when the patient has never had spontaneous menstruation, secondary when the absence of monthlies settles after the existence of more or less regular cycles, finally, primary school if monthlies occurred under treatment, but never spontaneously.
Spaniomenorrhea: it is defi ned by long cycles (≥ 35 days) regular or irregular.
Menorrhagia, metrorrhagia and menorrhagia: the first correspond to heavy periods, the seconds defi ne by bleeding between periods, the third fi nally are the combination of the two.
Genital bleeding: it matches any bleeding externalized through the vulva, whatever its origin: uterine, vaginal or cervical and abnormal by its abundance or its time of occurrence in the cycle.
After determining the source of bleeding by a speculum examination and the nature of cycle disorder, diagnostic orientation and therapeutic management may be decided, also conditioned by the age of onset of symptoms.
We distinguish four different periods:
– Period of active sexual life;
The working diagnosis and treatment depend on the age of discovery.
The menstrual disorders two years after menarche are common and correspond to the period of maturation of the hypothalamic-pituitary-ovarian. More than half of anovulatory cycles in the first year following monthlies (Fig. 1). It is not necessary to achieve a balance in the 2 years after menarche.
Diagnosis and etiology:
Primary amenorrhea requires an etiological investigation when it persists at the age of 16. The diagnostic orientation is a function of pubertal development and values of gonadotropins.
Lack of pubertal signs:
In the absence of pubertal signs, the dosage of gonadotropins (LH-FSH: follicle stimulating hormone and luteinizing) orients the diagnosis:
– High-LH FSH: primary ovarian failure; Normal or low FSH-LH: congenital hypogonadotropic hypogonadism or tumor (Figure 1).
Normal pubertal development:
Two mechanisms are considered: an abnormal birth canal preventing the normal flow of menstrual flow, a hormonal abnormality, regardless of its etiology.
It easily removes an anatomical cause locoregional:
– Imperforate hymen, cervicovaginal malformations usually revealed by menstrual pain at the age of menarche; DRE finds the hematocolpos;
– Has génésies Müllerian, Rokitansky-Kuster-Hauser syndrome (uterovaginal agenesis) the examination include a vaginal cup but the uterus is absent; the ovaries are perfectly normal;
– An isolated breast development without puboaxillaire hair (sometimes a slight axillary down any) associated with a blind vagina evokes an androgen resistance syndrome (abnormal functioning androgen receptor). LH is high, normal FSH, plasma testosterone is increased (4-5 times the male rate), the karyotype is masculine (XY). The removal of intra-abdominal or inguinal testes is imperative (risk gonadoblastoma). Hormone estrogen and progestin therapy is prescribed after castration.
In the absence of an anatomical defect, the dosage of gonadotropins orients the diagnosis:
– FSH and LH high: Premature ovarian failure: hypothalamic-pituitary cause, whatever the cause, genetic, iatrogenic or functional;
– Normal FSH, LH increased: polycystic ovary syndrome;
– FSH, LH normal or low: central cause, functional or organic.
Treatment depends on the cause.
If impuberism an estrogen substitution with progressively increasing levels allows the acquisition of secondary sexual characteristics, and by providing the appearance of a progestin substitution hemorrhage.
This treatment should be considered in specialized pediatric setting.
In case of polycystic ovary syndrome in pubertal revelation, the treatment is the same as in case of secondary amenorrhea (see above).
Spaniomenorrhea, secondary amenorrhea:
Diagnosis and etiology:
Often transient and functional, the spaniomenorrhea now has to look for certain causes. The causes of secondary amenorrhea are identical.
Presence of clinical hyperandrogenism (hirsutism, seborrheic alopecia, acne):
Most frequently, it is a polycystic ovary syndrome which is revealed at puberty.
It combines anovulation, clinical or biological hyperandrogenism and frequently overweight and android-type (waist circumference> 80 cm) and insulin resistance.
At puberty, it is difficult to distinguish physiological hyperandrogenism. The time resolution of spaniomenorrhea is reassuring.
Hyperandrogenism can be witness to a congenital adrenal hyperplasia late-onset (block 21-hydroxylase). Only the dosage of 17-hydroxyprogesterone to 8 hours and after immediate Synacthen injection allows to diagnose it (under stimulation value ≥ 10 ng / mL).
Much more rarely, Cushing’s syndrome can be found but signs of hypercortisolism are at the forefront.
Exceptionally, androgen secreting tumors can be discovered, severe hyperandrogenism leading to a rapid virilization of the patient.
No signs of hyperandrogenism:
Rarely, spaniomenorrhea may be a sign of primary ovarian failure, whether congenital (gonadal dysgenesis), autoimmune or iatrogenic (chemotherapy or radiation).
The prevalence of premature ovarian failure is estimated at 2% of the female population.
Hot flushes are frequently found. Gonadotropins FSH and LH are high.
The concept of family land “early menopause” must be sought.
The spaniomenorrhea may exceptionally meet in birth defects mentioned above (mutations of the FSH receptor, GnRH, Kal Kal-1 and-2 mutations), necessitating specialized genetic footprint.
If spaniomenorrhea persists two years after menarche, the following balance is achieved (Fig. 2):
– LH and FSH, estradiol to screen for primary ovarian failure. LH can be increased in the polycystic ovary syndrome, elevated FSH and LH shows a primary ovarian failure;
– Pituitary MRI in the presence of a failure or gonadotropic hyperprolactinemia;
– Androstenedione, testosterone;
– With 17-hydroxyprogesterone test Synacthen;
– If overweight and hyperandrogenism: SHBG (sex hormon binding globulin), blood sugar and insulin levels to discuss;
– Possibly a pelvic ultrasound to determine ovarian appearance.
Treatment depends on the cause:
– Polycystic ovary syndrome with clinical manifestations of hyperandrogenism: cyproterone acetate (Androcur®) 1 tablet / day for 20 days on 27 associated with 2 mg estradiol;
– Polycystic ovary syndrome without hyperandrogenism or moderate: progestin 10 days per month for the regularization of cycles; example: dydrogesterone (Duphaston®), chlormadinone acetate (Lutéran®) or micronized progesterone (UTROGESTAN®);
– Polycystic ovary syndrome and the need for contraception: contraceptive estrogenic climate (Jasmine® Diane 35®, Triafemi®);
– Primary ovarian failure: replacement therapy estrogens and progestins either orally in the absence of cons-indications (eg Climaston® 2/10) or extradigestive route (Estreva®, 3 pressures per day 25 days per month, and Utrogestan ® 200 mg from the 16th to 25th of the month, enabling the appearance of withdrawal bleeding, amenorrhea is usually resented).
Contraception may be recommended if necessary (loss of fertility is not absolute when installing the primary ovarian failure).
Treatment of gonadotropin deficiencies depends on the cause. In general, substitution treatment is desirable because it helps prevent osteoporosis long term and short term maintains trophicity genitals.
In case of functional hypothalamic amenorrhea, consider contraception as the resumption of ovulatory cycles is perfectly possible.
Pubertal uterine bleeding:
It affects 2-5% of adolescents. Most often these are functional pubertal bleeding related anovulation.
However hemostasis disorders may beings revealed during first cycles.
A rare but serious situation is the revelation of a haemorrhagic disease during the first period. It is urgent to assess the extent of bleeding and hemodynamic repercussions. If necessary, there must be urgent blood tests: blood count (CBC), rhesus, looking for irregular antibodies, coagulation profile.
Diagnosis and etiology:
In cases of suspected bleeding disorders, interrogation often found hemorrhagic field: epistaxis, postoperative bleeding during tonsillectomy, gingival, etc.
You can meet deficits in factors V, VII, VIII, X, von Willebrand disease, thrombopathies (Glanzmann’s disease, Bernard and Soulie, etc.).
After evaluating the hemodynamic consequences of bleeding, a first-line assessment is essential:
– NFS, platelets;
– Prothrombin time, activated partial thromboplastin time;
– Bleeding time by the method of IVY;
– Factor VIII;
– Von Willebrand factor antigen;
– Von Willebrand factor ristocetin cofactor.
In cases of severe bleeding, hospitalization is required and specific treatments can be administered. Estrogens at high doses associated with progestin allow the restoration of the endometrium relayed by a oestroprogestative normodosée pill. In case of contraindication to estrogen, progestin associated with antifibrinolytic are offered.
Finally organ damage can cause genital bleeding, to seek by careful clinical examination; bleeding then appear haphazardly, not by rhythmic cycles, sometimes associated with pelvic pain. In exceptional cervicovaginal or secreting ovarian tumors and mostly pelvic infections and complicated denied pregnancies can be found. Be aware raise the possibility of vulvar trauma.
After exclusion of other causes, functional etiology can be retained. The absence of ovulatory cycles with alternating spaniomenorrhea and hypermenorrhea is at the origin of bleeding.
Treatment involves an antifibrinolytic (tranexamic acid: Exacyl®, Spotof®, 2-3 g / d during menstruation) in ulcerative period and a progestin 10 days per month (Duphaston®, UTROGESTAN®, Lutéran®, etc. ).
A oestroprogestative contraception can also be provided in case of contraceptive need.
GENITAL IN ACTIVE PERIOD:
After eliminating clinically pregnancy, we must mention:
– By history, locoregional cause, uterine synechia mainly a post-curettage (oligomenorrhea and amenorrhea);
– Endocrine cause: hyperprolactinemia (galactorrhea fickle) most frequently, polycystic ovary syndrome if signs of hyperandrogenism, hypo- and hyperthyroidism, Cushing’s syndrome; a functional hypothalamic cause:
– Thinness, dietary restriction, anorexia nervosa;
– Premature ovarian failure (flushing);
– Any disease affecting the general condition.
The suspicion of a local cause requires the completion of a genital ultrasound and possibly a hysteroscopy for diagnosis.
In a woman normally set before the onset of spaniomenorrhea must look for:
– An early ovarian failure; flushing and alternating with short cycles are frequently found;
– A polycystic ovary syndrome, which is then accompanied by signs of hyperandrogenism and often overweight; it is unusual that this syndrome is revealed after thirty years;
– Idiopathic dysovulation, favored context of stress and overwork;
– Any general or endocrine disease can disrupt the menstrual cycle and clinical examination must be comprehensive: hypo- or hyperthyroidism, Cushing’s syndrome, renal failure etc.
Whether amenorrhea or spaniomenorrhea, diagnostic orientation and treatment decisions are identical to those of secondary amenorrhea the teenager.
Additional examinations before amenorrhoea or spaniomenorrhea are summarized in Figure 3.
We must mention:
– Complicated pregnancy: spontaneous miscarriage, ectopic pregnancy requiring urgent dosage of hCG;
– A cause uterine: submucosal fibroids (clots), polyps (bleeding), endometrial hyperplasia, adenomyosis (pain associated with bleeding);
– An infectious cause: cervicitis, endometritis, chlamydial infection, according to evoke the context (multiple partners, early age) associated with pelvic pain most often and hence the need for bacteriological samples. Bleeding cervicitis are readily caused (appearing after sex), the cervix is congested, mucus may be purulent;
– Neoplastic causes: cervical cancer (uncontrolled bleeding of low abundance), endometrial cancer after 40 years;benign ovarian tumor or rarely malignant;
– A functional cause: endometrial atrophy as progestins or hormonal, ovulatory dysfunction with luteal insufficiency especially common in perimenopause;
– A disorder of hemostasis acquired: peripheral thrombocytopenia (immune thrombocytopenic purpura) or central (blood diseases, aplastic), hypoprothrombinémies (treatment with vitamin K antagonists, cirrhosis);
– Iatrogenic cause: copper intrauterine devices cause menorrhagia, inadequate treatment to estrogen or progestin causes more readily spotting.
The pelvic examination can locate the source of bleeding: endo-uterine, cervical or vaginal. It allows to check the appearance of the cervix and perform according to the context an endometrial biopsy or bacteriological samples.
The smear test should not be conducted during the bleeding episode, but if the appearance of the cervix is suspicious, biopsies should be performed. The vaginal search an increased volume of the uterus, an adnexal mass.
In all cases, an assessment of iron deficiency loss must be made by performing a blood count and serum ferritin.Indeed some women tolerate significant menorrhagia for many years associated with repeated pregnancies can cause severe anemia.
Depending on the clinical setting the record is completed by genital ultrasound that allows for the diagnosis of uterine benign lesions: submucosal fibroids, polyps, endometrial hypertrophy and adenomyosis.
Any abnormality of the endometrium should carry out a hysteroscopy diagnostic and therapeutic: biopsy hyperplasia, excision of a polyp resection of submucosal myoma.
After eliminating organic pathology, we retain the diagnosis of dysfunctional uterine bleeding or by endometrial atrophy, particularly in progestogen contraception and sometimes under oestroprogestative contraception.
In all cases the endometrium is very fine in ultrasound.
The therapeutic management of dysfunctional uterine bleeding depends on the need for contraception (Fig. 4).
In case of need for contraception, are avoided microprogestatifs and we can then provide a device Intrauterine levonorgestrel (Mirena). If contraception is desired Estrogen, progestin generation change and ethinyl estradiol dosage can be tried. Intrauterine devices copper are not recommended because they are the cause of menorrhagia.
With no need for contraception, provision of progestin from the 16th to 25th day of the cycle helps regulate and reduce menstrual flow.
Myometrial pathologies, polyps should be supported surgically.
The time before the final adoption of the monthlies of variable duration from one woman to another, is marked in the vast majority of cycle disorders.
Initially, the cycles become shorter (less than 26 days) and then appears alternating period of short cycles and spaniomenorrhea before leading to amenorrhea.
Parallel appear hot flashes alternating with mastodynia and menorrhagia, signing the poor quality of ovulation and progesterone deficiency (relative hyperestrogenism).
After removing an organic cause very common at this age, by genital ultrasound or hysteroscopy, it is possible to treat these disorders by providing a pregnane type of progestogen (chlormadinone acetate: Lutéran®) or the norpregnane 16th to 25th day of the cycle.
If contraceptive need, for example there is provided a norpregnane progestin or pregnane 20 days on 27.
Never trivialize perimenopausal bleeding, an exploration is essential.
Any bleeding that occurs after menopause deserves exploration at least ultrasound to assess the endometrium which must be atrophic.
When in doubt hysteroscopy is required (endometrial thickness greater than 4 mm). Indeed at that age, cancer of the endometrium must be removed (peak incidence between 55 and 59 years). High blood pressure, Type II diabetes and obesity are often associated with ground promoting endometrial neoplasia.
The cervical neoplasia may also occur in this age where women are not screened.