EM treatment aims and guidelines: removal of lesions, pain relief, promotion of fertility, and reduction of recurrence
Clinical typing of EM: peritoneal type, ovarian type, deep vaginal-rectal compartment nodular type, other sites of endometriosis (covering myometriosis).
primary treatment: surgery and pharmacological treatment.
Surgery does not solve all the problems (does not change the pathophysiological situation, does not exhaust the focal problems, recurrence problems, etc.), medication is necessary.
Mechanisms of occurrence: hormonal levels, genetic and other related.
Main drugs.
1. contraceptives (progesterone + estrogen) to improve symptoms, inhibit ovulation, methylation, atrophy and absorption of ectopic endometrium.
Indications: indicated for those who do not want to have children with mild lesions.
Dosage: Start taking 1-2 tablets/day on the 5th day of menstruation for 3 months, change to cycle for 3-6 months.
Efficacy: 90-100% relief of symptoms with insignificant changes in signs (containing estrogen, cysts and nodal foci may grow).
Side effects: same as contraceptive pill side effects, 1-2 months after stopping the pill to resume ovulation.
2. False pregnancy therapy: Highly effective progestogen Medroxyprogesterone acetate – 17α hydroxyprogesterone derivative (long-acting contraceptive injection).
Dosage: Start dosing (300mg) on the 1st day of menstruation, once every 3 months for 6 months.
Efficacy: 60-90% symptom relief rate, 20-40% pregnancy rate, 68% relapse rate with discontinuation of the drug.
Side effects: no androgenic effects, insignificant liver damage, significant breakthrough bleeding, inhibition of ovulation, sodium and water retention.
3. Mifepristone: Ru486 progesterone receptor antagonist, small dose application can cause atrophy and absorption of ectopic endometrium, resulting in amenorrhea and improvement of pain.
Mechanism of action: Antagonize the action of progesterone, act on hypothalamus-pituitary to make FSH and LH decrease (actually antagonize both estrogen and progesterone), increase endogenous prostaglandin release, reduce uterine artery blood flow, and shrink uterine fibroids.
Dosage: 10-25mg/day for 6 months starting on the 1st-3rd days of menstruation.
Efficacy: symptom relief rate of 90-100%.
Side effects: loss of appetite, fatigue, nausea, weight loss, hypokalemia, significant rebound of symptoms after discontinuation of the drug.
No problem with the efficacy of the drug, ethical issues exist.
4. Pseudo-menopausal therapy: Danazol 17α ethinyl testosterone derivative (fast oral absorption, fast metabolism, half-life 4-5 hours, hepatic metabolism, renal excretion).
Mechanism of action: acts on hypothalamus-pituitary gland to make FSH and LH fall; binds to PR and ER; promotes RNA synthesis of androgens, binds to sex hormone-binding globulin, free testosterone rises, has obvious androgenic effects (androgenic problems are obvious, applied as of the 1990s, now drug-free).
Dosage: Start taking 400-800mg/day on the 1st-3rd days of menstruation for 3-6 months.
Efficacy: 87.5-100% improvement in symptoms and signs, resumption of menstruation within 6-8 weeks after discontinuation of the drug, 50% pregnancy rate, mostly occurring six months to one year after discontinuation of the drug, 39% relapse rate 3 years after discontinuation of the drug.
Side effects: significant weight gain, liver function abnormalities, androgenic reactions (hirsutism, acne, seborrhea, voice changes, abnormal vaginal bleeding).
Progesterone: oral agent of choice in pseudo-menopausal therapy.
Biological activity: anti-gonadotropin, strong anti-progestin (of little significance in this disease), moderate anti-estrogen, weaker estrogenic and androgenic activity.
Dual action: axis inhibition (no ovulation peak) + ER PR receptor inhibition, high safety, low toxicity, no accumulation.
Pharmacokinetics: prodrug acts independently of metabolites and is metabolized by the liver and excreted by the kidneys.
Application: Start taking 2.5mg on the 1st day of menstruation, 2 times a week for 3-6 months.
Preoperatively, depending on the condition, minimum 3-4 months, preferably 6 months; postoperatively, the medication is used for 3-6 months.
Good efficacy: 100% symptom relief rate (dysmenorrhea, non-menstrual pain, painful intercourse, tenderness, etc.), 50-80% improvement in signs (best improvement in peritoneal type, followed by improvement in ectopic cysts, limited improvement in nodules), mean return of menstruation in 21 days after stopping the drug (ovulation rate in the 1st period is less than 80%), and 56-64% pregnancy rate at the end of treatment. One study of EM combined with infertility: surgery (to separate the adhesions and remove the lesion) followed by the drug, 60% pregnancy rate.
Side effects: varying degrees of weight gain (generally less than 3kg); some patients experience a transient single transaminase rise above side effects are mild and reversible, if the ALT continues to rise above 80, biphenyldiphenhydramine + vitamin c, normal can continue to be applied; continued rise in discontinuation of the drug, transfer to infection unit.) ; bleeding during treatment: the incidence of complete amenorrhea during treatment is 18.8%, and the incidence of those with menstrual-like bleeding or breakthrough bleeding completely without amenorrhea is 20.8% (3 tablets per week, 10%; related to insufficient endometrial support, individual differences problems, relatively low dose drug application problems). However, the treatment effect is not affected in those with breakthrough bleeding, and the bleeding condition can be improved (add 1 tablet per week for 3 weeks and then reduce back; or stop withdrawing 1 time and take the drug again with the same effect). No effect on bone density; relapse rate: 12-17% in six months, 23% in one year, 32% in two years, 32% in three years
GnRH mechanism of action.
1, “reversible drug depot”, inhibition of hypothalamic-pituitary presynaptic substances, inhibition of FSH, LH, inhibition of E2, P release. Treatment of hormone-dependent diseases: EM, endometrial cancer, prostate cancer (testosterone decline), breast cancer.
2.Stop central precocious puberty: early initiation of the axis, early puberty (early development of bone enough to close prematurely; premature ovarian failure. (Can be given in half amount to pediatric application for 6 months, every 4-5 months for 6 months, normal age of menstruation stop).
3.Control of gonadotropin secretion kinetics: IVF, applied before ovulation promotion, and then ovulation promotion to synchronize egg growth and good quality to improve the level of pregnancy assistance.
4, gynecological tumor treatment: ovarian cancer (epithelial cancer), breast cancer, uterine fibroids, uterine adenomyoma, endometriosis, etc.
There are 3 problems with GnRHa.
Short-term stimulation of FSH and LH elevation, “ignition effect (flare up)”, which can worsen symptoms such as bleeding.
Insufficient blockade can occur after desensitization of the pituitary GnRH (about 2-3 weeks).
oral administration can be destroyed by the gastrointestinal tract and must be injected
Reverse addition therapy: the need for reverse addition and the choice of which regimen is currently undefined and routine and needs to be individualized.
Hypoestrogenemia, osteoporosis, need for reverse addition.
Pregnant trienone side effects mildly reversible; GnRH side effects, osteoporosis more difficult to correct; no significant difference in recurrence rate between the two. Pregnant trienone can be used as a continuation medication after 3 months of GnRHa application (in case of insufficient injection dosage or if it is not tolerated). Both progesterone and GnRHa can be repeatedly applied, such as a break of 3 months and then continued application.
5, GnRH inhibitors: Cetrorelix Ganirelix effect is stronger than GnRHa (while acting on GnRH1 – for the axis and GnRH2 – for the placenta, tissue, endometrium and other local effects), individualized amount calculated according to the body surface area.
Aromatase inhibitors: Aromatase is the rate-limiting enzyme of estrogen synthesis and catalyzes the conversion of androstenedione and testosterone to estrone and estradiol; it affects the progesterone or pregnenolone copper pathway to promote estrogen synthesis. Aromatase inhibitors can inhibit estradiol synthesis and treat EM.
In conclusion: EM pharmacotherapy is still based on hypothalamic-pituitary-gonadal axis inhibition, GnRHa is the preferred injectable drug for pseudo-menopause treatment, and progesterone is the preferred oral drug for pseudo-menopause treatment, both of which can complement each other.