Hormone replacement therapy for menopause

Traitements hormonaux substitutifs de la ménopause

Menopause is the permanent cessation of the rules by depletion of ovarian follicle capital. The little girl born with a stock of follicles (200,000 à 500,000) which will be exhausted in the course of life primarily by atresia, but also when entering in the growth phase of follicular cohorts allowing one of them to reach the pre-ovulatory stage.

On average, menopause occurs around the age of 50 years, stable through the centuries. It clinically translates:

– The climacteric syndrome: flushing, night sweats, weakness, nervousness, joint pain, mood disorders or depression, insomnia;

– Trophic urogenital disorders;

– Bone demineralization leading to osteoporosis in 30% of women.

Menopause is preceded by a period of irregular cycles, shorter (shortened follicular phase, ovulation 10th, 11th days of the cycle) and that lengthen with anovulation. Hot flashes and night sweats especially menopause may precede by several months or years.

The diagnosis is clinical: amenorrhea for 12 months with hot flashes in women 50 years. A test progestin to confirm the diagnosis: 10 days per month addition of a progestin for three months; no withdrawal bleed reflects the absence of estrogenic impregnation.

There is no indication to dose FSH (Follicle-Stimulating Hormone) and LH (luteinizing hormone) outside the hysterectomy patients.

Hormone replacement therapy for menopause
Hormone replacement therapy for menopause

INDICATIONS:

Until 2002, hormone replacement therapy (HRT) for menopause was prescribed in three main directions: climacteric signs, prevention of osteoporosis and prevention of cardiovascular events.

Since the publication of several US randomized studies (HERS, secondary prevention study and the WHI, primary prevention study), the indications were restricted by Anaes and Afssaps, although the products used were completely different from those are used in France and elderly populations treated (66 years on average in 63 years in HERS and WHI) do not reflect all risks of French women and 50 years.

Currently, the only indication retained is the symptomatic treatment of climacteric symptoms for the shortest possible and the lowest effective dose duration.

The prevention of cardiovascular events has been questioned by the results of such studies; secondary prevention, HRT is against-indicated due to an increased risk of accidents on HRT (oral conjugated estrogens and medroxyprogesterone acetate) based on the results of HERS. In primary prevention, venous and arterial thromboembolic risks are increased by the administration of HRT in the US; However a French case-control study showed no increased risk with extradigestive route (ESTHER study).

Regarding the increased risk of breast cancer on HRT, it seems to be confirmed in studies for more than 5 years use especially with synthetic progestins; this explains the indication prevention of bone risk was removed, Afssaps considering that the risk profi balance was unfavorable. The risk might be different with estradiol and natural progesterone, but the decline is still low (French E3N study).

TREATMENT PRINCIPLES:

Estrogen:

The estrogen can be administered orally in the absence of metabolic or vascular-indication against but preferably such tradigestive path patch, percutaneous gel or nasal spray. Frost and patches should not be applied on the breasts. Current recommendations are to start with the minimum dose and then adjust the dose according to symptoms.

Transdermal patches are weekly or bihebdomadiaires and the dosage varies from 25 to 100 mg, the average dose is 50 micrograms / 24 hours patch 1.5 mg of 17-beta-estradiol gel; This dose will be tailored to the age, needs to estradiol decreases especially at bone level with age. Percutaneous application allows individual adjustment based on signs or underdosing. There is also a nasal spray having the same advantages as the patches: Aérodiol®.Combined patches containing estrogen and progestin exist and are sometimes interesting when one wishes to avoid the phenomenon of first-pass including progestin. (Femsept Combi®, etc.).

Progestin:

The progestogen will be of natural progesterone or its derivative (micronized progesterone, dydrogesterone), or a close synthetic progestin (pregnane derivative: chlormadinone acetate, medrogestone, promegestone …). Its role is to prevent the occurrence of endometrial hyperplasia or endometrial cancer. The dose range is 100 to 200 mg for progesterone depending on the selected scheme and the need to be more or less atrophic endometrium for. For example:

– Estreva® three daily pressures of J1 to J25;

– Progesterone 100 mg: 1 capsule at bedtime J1 to J25.

The classic pattern, without rules, combined with the taking estrogen and progesterone simultaneously 25 days per month, keeping few days without treatment.

A sequential scheme is possible for women wishing to keep their rules and then includes 25 days of estrogen associated with at least 12 days of progestin then double dose of this e is administered continuously.

Example:

– Oesclim® 50: 1 Patch 2 times per week, 3 weeks out of 4;

– Progesterone: 200 mg of J14 to J25.

– In women with prior hysterectomy, the consensus is not to administer progestin. For example: OEstrodose®, 2 daily pressures of J1 to J25, treatment for 6 months.

ASSESSMENT AND MONITORING PRETREATMENT:

Appraisal:

Before prescribing HRT, it is necessary to confirm menopausal status (test progestin or dosage of FSH + LH if hysterectomy).

The indication for HRT will be given if the patient seeks care for climacteric signs that adversely affects the quality of life.

Against the relative or absolute will then be sought:

– Personal history of breast atypical hyperplasia or breast cancer, and family background evocative of particular neoplastic risk factor;

– Cardiovascular venous or arterial thromboembolic events;

– Combinations of several cardiovascular risk factors: hypertension, smoking, diabetes, dyslipidemia, obesity, family plot.

Theoretically HRT is against-indicated when there is venous or arterial stroke, heart attack, stroke. However prudent prescription by a specialized team is possible if the quality of life is really affected by the climacteric syndrome, particularly as part of venous accidents. It seems that the small increase observed in arterial accidents WHI and HERS was due partly to increased clotting products (which can be deleted with the HRT “French”) and the detachment of unstable plaques by estrogen (with unknown behavior with our treatments) explaining the occurrence of accidents in the first year of use …

A pretreatment investigations include at least:

– A screening mammogram before starting treatment;

– Metabolic balance.

Surveillance:

The effectiveness of treatment should be reassessed after three months and then every six months for signs of hyperestrogenism, especially mastodynia that impose lower doses of estrogen.

Mammography should be renewed even earlier (18 months or 12 months) due to an increase in breast density making them less sensitive mammograms and breast ultrasound should be recommended if increased breast density.

Regular therapeutic windows are indicated to assess the need for further or not HRT since the climacteric signs tend to decrease with time. If necessary, treatment can be continued by offering the lowest effective dose.

Breakthrough bleeding on HRT require the same explorations (pelvic ultrasound, hysteroscopy) any postmenopausal metrorrhagia, after verifying the absence of HRT use error.

The consultation is an opportunity for menopause to track:

– Metabolic disorders by blood glucose and lipids, and blood pressure, smoking, obesity;

– Neoplastic risk factors, especially breast and endometrial cancers;

– Osteoporosis risk factors (history of fracture before age 40 or family, prolonged immobilization or physical inactivity, body mass index less than 19 kg / m2, premature ovarian failure or estrogenic deficit factor, smoking, alcoholism, low intakes of calcium and vitamin D, long-term corticosteroid, hyperthyroidism, hyperparathyroidism, Cushing’s syndrome). Bone densitometry may be proposed if HRT prescription is not considered;

– Urinary tract disorders and pelvic floor which may worsen. perineal re-education can be proposed.

Finally, from a forensic point of view, given the epidemiological data, it must inform the patient of the increased risk of breast cancer after 5 years of use (relative risk = 1.26, recalling that a smoker has a relative risk of 20 of developing lung cancer).

Menopause consultation is also an opportunity to clarify the right diet and lifestyle rules: low fat diet, tailored to the body mass index and potential risks, smoking cessation, exercise: at least a half hour brisk walk daily or 2 hours of sport a week.

ALTERNATIVE THERAPY:

In case of medical indication against-or if the patient does not want HRT, alternatives can be proposed.

Hot flashes:

Hot flashes can be improved by:

– Micronized progesterone, 100 mg daily continuously in the evening;

– Abufène®, (beta-alanine) 1-3 cp / d into 5 to 10 days treatment, very good tolerance, very moderately effective;

– Effexor®, the dose of 25 to 37.5 mg / day, off-label;

– The Livial® (tibolone) is an androgen and progestin norsteroid estrogenic potential acting both on climacteric signs and vaginal dryness. He opposes the decrease in bone density. The thromboembolic risk is present in theory given the product class and the effects on the breast and long-term bone (fractures) are not yet known. weight gain and manifestations of hyperandrogenism are possible.

It may be useful to start which improves the weight tolerance half dose. It is to be reserved as second-line to women with climacteric signs and intolerance breast estrogen because it does not give mastodynia. It is not reimbursed by Social Security. A recent British study (Million Women study) reported an increased relative risk of endometrial cancer with tibolone. It may be prescription bias, women who most often taken estrogen alone before tibolone; it is absolutely imperative to explore how patients who have postmenopausal bleeding whether in or without HRT.

Vaginal dryness:

Vaginal dryness and urogenital trophicity can be improved by providing local estrogen cream and eggs, for example:

– Colpotrophine® 1 vaginal capsule 2 times a week;

– Colpotrophine® cream, 1 vulvar Application 2 times a week.

Many other pharmaceutical products comprising either estriol (Gydrelle®, Physiogyne®, Trophicrème®) or the promestriene (Colposeptine®, Colpotrophine®) exist on the market.

Fracture risk:

The fracture risk can be managed by lifestyle measures associated with taking calcium and vitamin D.

Established osteoporosis by bone densitometry especially at a young age must seek a secondary cause (vitamin D deficiency, hyperparathyroidism …). It will eventually be processed by the contribution of bisphosphonates.

These treatments are only reimbursed in osteoporosis with at least one fracture.

SERMs (selective estrogen receptor modulators) are beings proposed in the management of osteoporosis: Evista® and Optruma® (raloxifene) and have proven effective in prevention and treatment of osteoporosis with 1 cp / d allowing a reduction in vertebral fractures (not shown for hip fractures). There is an increased risk of venous thromboembolism against showing these treatments-if history, or land at risk. Hot flashes can also be aggravated. As bisphosphonates, they are reimbursed only if there is at least one ostéophytique fracture.

Phytoestrogens:

Phytoestrogens are in 60% of cases a good efficacy on hot flushes, but the lack of studies does not allow us to recommend them. They have no effect on the trophic vulvovaginal.

In conclusion, we must emphasize the lifestyle more important than ever at this time of the woman’s life to change to the better course, and if necessary to best use the drug panel at our disposal.