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HRT (Hormone Replacement Therapy) and DRIM (Drugs and Roentgen Induced Menopause) M. Luerti Dipartimento Materno Infant

HRT (Hormone Replacement Therapy) and DRIM (Drugs and Roentgen Induced Menopause) M. Luerti Dipartimento Materno Infantile U.O. di Ostetricia e Ginecologia - Presidio di Lodi ASL della Provincia di Lodi - Regione Lombardia - Italia. HRT and DRIM.

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HRT (Hormone Replacement Therapy) and DRIM (Drugs and Roentgen Induced Menopause) M. Luerti Dipartimento Materno Infant

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  1. HRT(Hormone Replacement Therapy)andDRIM(Drugs and Roentgen Induced Menopause) M. Luerti Dipartimento Materno Infantile U.O. di Ostetricia e Ginecologia - Presidio di Lodi ASL della Provincia di Lodi - Regione Lombardia - Italia

  2. HRT and DRIM Notwithstandingincreasing epidemiological frequency of DRIM mainly because of diffusion of recent drugs: • Chemotherapies • GnRH analogues • Danazol • Gestrinone knowledge about this topic is rather lacking

  3. FACTORS AFFECTING DRIM • Disease motivating the induction of menopause • Ovarian failure inducing agent • Postmenopausal ageing in relation to the age at which menopause occurs

  4. DISEASES MOTIVATING THE INDUCTION OF MENOPAUSE Lymphomas Breast cancer Leukaemia Auto-immune diseases Soft tissue cancer Endometriosis Wilms tumor Uterine myomas Osteosarcoma Persistent menorrhagia Trophoblastic tumors Cardiovascular diseases

  5. PRIMITIVE DISEASECAN EXACERBATE SOME SYMPTOMS Disease Symptoms Cancer Sexual life deterioration Anxiety Endometriosis Depression Sleeplessness Cardiovascular diseases Fatigue Anaemia Osteoporosis Dyspareunia

  6. FACTORS AFFECTING PROBABILITY OF OVARIAN FAILURE • Age of the patient • Duration of treatment • Dose • Fractionation of doses • Association of agents (polichemotherapy)

  7. FOLLICLE RESERVE IN WOMEN OF DIFFERENT AGES Age Average n. of primordial Extreme limits follicles Birth 480.000 260.000-750.000 15-30 150.000 40.000-300.000 31-40 75.000 15.000-200.000 > 40 8.000 350-25.000

  8. CHEMOTHERAPY AND OVARIAN CYTOTOXICITY Definite Probable *Chlorambucil *Doxorubicin *Cyclophosphamide *Vinblastine *L-Phenylalanine Mustard *Cytosine Arabinoside *Nitrogen Mustard *Cisplatin *Busulfan *Nitrosureas *Procarbazine *m-AMSA *Etoposide Unknown Unlikely *Bleomicin *Methotrexate *Fluorouracil *Mercaptopurine *Vincristine

  9. OVARIAN FAILURE INDUCING AGENTS Reversible Hormones Irreversible 53% irreversibleunder age 35 Chemotherapy 84% between ages 35-44 94% age 45 or older Reversible (< 250 r/ovary) Radiotherapy Irreversible (> 250 r/ovary)

  10. OVARIAN FAILURE INDUCING AGENTS CAN EXACERBATE SOME CLIMATERIC SYMPTOMS Agent Symptoms Fatigue Chemotherapy Anaemia Hormonal therapy Cardiovascular disease RadiotherapyOsteoporosis Atrophy and dyspareunia

  11. POSTMENOPAUSAL AGEING The lower the age of induced menopause, the stronger the symptoms and higher the risk of long-term effects

  12. CONSEQUENCES OF SUDDEN OVARIAN FAILURE Surgical removal of both ovaries constitutes the better model to represent DRIM and its consequences on symptoms associated Evident increase of vaginal atrophy Evident decline of sexual activity

  13. CONSEQUENCES OF SUDDEN OVARIAN FAILURE The model based on surgical induction of menopause is the most important suitable and shows: • A higher osteoporotic risk • A higher cardiovascular risk • A net increase in the frequency of vaginal atrophy and decline of sexual activity

  14. CLIMATERIC SYNDROME IN DRIM The climateric syndrome in DRIM is more severe than in natural postmenopause, mainly due to increased intensity of psychoemotional complaints (nervousness, depression, insomnia and fatigue), largely due to the stress involved in DRIM

  15. LONG-TERM EFFECTS IN DRIM The risk of long-term effects in DRIM is higher than in natural postmenopause, mainly due to: • the action of ovarian failure inducing agent • postmenopausal ageing

  16. HRT and DRIM HRT should be useful in DRIM even more than in spontaneous menopause Unfortunately the intensity of the symptoms and consequences of DRIM is in contrast with the reluctance of the physician to treat patients

  17. RELUCTANCE OF THE PHYSICIAN: WHY? Is HRT contraindicated in DRIM? because of inducing agent? because of primitive illness?

  18. HRT and DRIM There are no contraindications to the use of HRT in DRIM in relation to ovarian failure inducing agent

  19. HRT IN PATIENTS TREATED FOR BREAST CANCER It is a general belief that HRT after breast cancer will increase the risk of developing recurrences, though there are no clear data available to support this suggestion

  20. RECURRENCES AFTER HRT IN PATIENTS TREATED FOR BREAST CANCER

  21. The National Cancer Institute of the United States, in 1996, initiated a randomised, prospective trial of HRT following treatment of breast cancer in women with Stage 1 and 2 disease.Inclusion criteria are:- disease free for 2 years with estrogen receptor negative disease - 10 years following a breast cancer with estrogen receptor status unknown

  22. RECURRENCES AND SURVIVAL AFTER HRT IN PATIENTS TREATED FOR ENDOMETRIAL CANCER

  23. HRT IN PATIENTS TREATED FOR OVARIAN CANCER

  24. HRT AND GYNECOLOGICAL CANCERfrom THE CANADIAN CONSENSUS CONFERENCE ON MENOPAUSE AND OSTEOPOROSIS, 1998 • Breast cancer:HRT may be offered after proper individual counselling • Endometrial cancer:HRT should not be withheld in treated Stage 1 or 2 Grade 1 or 2 • Ovarian cancer: HRT should not be withheld in these patients, after proper counselling • Cervical cancer: Several studies support the use of HRT in patients treated for squamous cell carcinoma of the cervix • Vaginal and vulvar cancers: There is no relevant published information indicating that HRT use has a negative effect on either squamous cell carcinoma of the vagina or the vulva

  25. HRT and OTHER CANCERfrom THE CANADIAN CONSENSUS CONFERENCE ON MENOPAUSE AND OSTEOPOROSIS, 1998 • Colo-rectal cancer:There are no data showing any change in risk associated with HRT in women who have been treated for colon cancer • Melanoma:cutaneous non-metastatic melanoma is not a contra-indication to the use of post-menopausal estrogen • Thyroid cancer: While it is recognized that, in post-menopausal women, well differentiated papillary and follicular carcinomas may be particularly aggressive, there is no evidence

  26. HRT after ENDOMETROSIS INDUCED MENOPAUSEfrom THE CANADIAN CONSENSUS CONFERENCE ON MENOPAUSE AND OSTEOPOROSIS, 1998 Combined estrogen and progestin replacementtherapy in standard doses does not appear to causeregrowth of endometriosis in menopausal women, or inyoung women receiving estrogen-progestin“addback”therapy following medical oophorectomy with GnRHanalogues. A small subgroup of women may experiencerecurrence of pain and other symptoms during unopposedestrogen therapy, particularly if residual diseaseremains following definitive surgery. There are anecdotal reports of endometrial cancerdeveloping in residual endometriosis in women receivingunopposed estrogen following definitive surgery forendometriosis. This appears to beone of the few indications for progestin therapy followinghysterectomy, either as part of a continuous-combinedregimen or as progestin-only therapy. Available datado not allow a definitive answer to this question.

  27. HRT after FIBROIDS INDUCED MENOPAUSEfrom THE CANADIAN CONSENSUS CONFERENCE ON MENOPAUSE AND OSTEOPOROSIS, 1998 Uterine fibroids do not constitute a contra-indication to HRT, but it should be used with caution in women known to have fibroids. Although both estrogen and progestinscan influence fibroid growth, the doses in conventionalHRT regimens are usually not sufficient to causeenlargement of fibroids. However, rapidgrowth or abnormalbleeding (from a submucous fibroid) requires investigationand possibly surgical intervention.

  28. HRT and DRIM HRT DOESN’T APPEAR TO BECONTRAINDICATED AND ADVISABLE IN MOST CASES OF DRIM

  29. HRT IN PATIENTS TREATED FOR BREAST AND ENDOMETRIAL CANCER It is recommended the use of a continuous combined estro-progestin therapy

  30. COMPLEMENTARY APPROACHES TO DRIM • Other medications Clonidine Bellergal® Topical estrogens High doses progestins Bisphosphonates SERMs • Diet and lifestyle • Phytoestrogens • Herbal remedies Cimicifuga racemosa Hypericum perforatum Ginkgo biloba Valeriana officinalis Evening Primrose Oil

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