Amenorrhea secondary prevention
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]
Overview
Effective measures for the secondary prevention of functional hypothalamic amenorrhea include oral contraceptive pills (OCPs), androgen therapy, recombinant insulin like growth factor 1 (IGF-1), recombinant leptin, bisphosphonates, and increasing calorie intake.
Secondary Prevention
- Effective measures for the secondary prevention of functional hypothalamic amenorrhea include:
Oral contraceptive pills (OCPs)
- Different studies have shown that OCP therapy can slow down the bone loss process in patients with exercise- and anorexia-associated amenorrhea. The detailed results are as following table:[1]
| Medicine | Dosage | Treatment duration | Bone mineral density (BMD) site | Outcome | |
|---|---|---|---|---|---|
| Ethinyl estrdiol | 0.035 mg | 12 months | Lumbar spine and femoral neck | Increased BMD in all sites[2] | |
| Norethindrone or
Medroxyprogesterone |
0.5-1.0 mg
10 mg | ||||
| Ethinyl estrdiol | 0.03 or 0.02 mg | 12 months | Lumbar spine | Increased BMD in all sites[3] | |
| Desogestrel | 0.15 mg | ||||
| Ethinyl estrdiol | 0.030 mg | 10 months | Lumbar spine and legs | Increase BMD in lumbar spine not in legs[4] | |
| Levonorgestrel | 0.150 mg | ||||
| Ethinyl estrdiol | 0.05 mg | 8 months | Lumbar spine and radius | Increase BMD in lumbar spine not in radius[5] | |
| Cyproterone acetate | 2 mg | ||||
| Conjugated estrogen | 0.0625 mg | 24 months | Lumbar spine and femoral neck | Increased BMD in all sites[6] | |
| Transdermal estradiol | 0.05 mg | ||||
| 12 days | Estriol | 1 mg | 9.3 months | Lumbar spine, femoral neck, and trochanter | No change BMD in any sites[7] |
| Estradiol | 2 mg | ||||
| 10 days | Estriol | 1 mg | |||
| Estradiol | 2 mg | ||||
| norethisterone | 1 mg | ||||
| 6 days | Estriol | 0.5 mg | |||
| Estradiol | 1 mg | ||||
| Premarin | 0.625 mg | 24 months | Lumbar spine, wrist, and foot | Increase BMD in lumbar spine, neither in wrist nor in foot[8] | |
| Provera | 10 mg | ||||
| Ethinyl estradiol | 0.035 mg | 10 months | Lumbar spine and femoral neck | Increase BMD in lumbar spine not in femoral neck[9] | |
| Norgestimate | 0.180–0.250 mg | ||||
Androgen therapy
- It is assumed that 50, 100, or 200 mg of micronized DHEA daily can increase bone mineral density (BMD), and prevent the osteoporotic fracture. But there is not any established long term study to prove this effect.[10]
Recombinant insulin like growth factor 1 (IGF-1)
- It is approved that using recombinant insulin like growth factor 1 (IGF-1) (30 μg/kg−1 twice per day) along with OCP (0.035 mg ethinyl estradiol and 0.4 mg norethindrone) secondarily prevents the fracture in hypothalamic amenorrhea, due to anorexia nervosa, with increasing bone mineral density (BMD).[11]
Recombinant leptin
- It seems that administering recombinant Leptin (0.08 mg/kg) subcutaneous daily for 2–3 months would result in increasing bone formation markers; though, decreasing fracture risk through secondary prevention.[12]
Bisphosphonates
- In adolescent women with anorexia-induced amenorrhea, alendronate (10 mg) with calcium (1200 mg) and vitamin D (400 IU) for a year show significant improvement in bone loss. Therefore, they can be used as secondary prevention.[13]
- The major uses of bisphosphonates as secondary prevention for functional amenorrhea are as following table.
Increasing calorie intake
- Raising the efficient calories in daily meal and also weight gain in women with anorexia- or exercise-induced amenorrhea can increase bone mineral density (BMD) and also decrease the long term complications (osteoporosis and fracture).[14][15][16]
References
- ↑ Vescovi JD, Jamal SA, De Souza MJ (2008). "Strategies to reverse bone loss in women with functional hypothalamic amenorrhea: a systematic review of the literature". Osteoporos Int. 19 (4): 465–78. doi:10.1007/s00198-007-0518-6. PMID 18180975.
- ↑ Hergenroeder AC, Smith EO, Shypailo R, Jones LA, Klish WJ, Ellis K (1997). "Bone mineral changes in young women with hypothalamic amenorrhea treated with oral contraceptives, medroxyprogesterone, or placebo over 12 months". Am. J. Obstet. Gynecol. 176 (5): 1017–25. PMID 9166162.
- ↑ Castelo-Branco C, Vicente JJ, Pons F, Martínez de Osaba MJ, Casals E, Vanrell JA (2001). "Bone mineral density in young, hypothalamic oligoamenorrheic women treated with oral contraceptives". J Reprod Med. 46 (10): 875–9. PMID 11725730.
- ↑ Rickenlund A, Carlström K, Ekblom B, Brismar TB, Von Schoultz B, Hirschberg AL (2004). "Effects of oral contraceptives on body composition and physical performance in female athletes". J. Clin. Endocrinol. Metab. 89 (9): 4364–70. doi:10.1210/jc.2003-031334. PMID 15328063.
- ↑ De Crée C, Lewin R, Ostyn M (1988). "Suitability of cyproterone acetate in the treatment of osteoporosis associated with athletic amenorrhea". Int J Sports Med. 9 (3): 187–92. PMID 2970444.
- ↑ Cumming DC (1996). "Exercise-associated amenorrhea, low bone density, and estrogen replacement therapy". Arch. Intern. Med. 156 (19): 2193–5. PMID 8885817.
- ↑ Gibson JH, Mitchell A, Reeve J, Harries MG (1999). "Treatment of reduced bone mineral density in athletic amenorrhea: a pilot study". Osteoporos Int. 10 (4): 284–9. doi:10.1007/s001980050228. PMID 10692976.
- ↑ Warren MP, Brooks-Gunn J, Fox RP, Holderness CC, Hyle EP, Hamilton WG, Hamilton L (2003). "Persistent osteopenia in ballet dancers with amenorrhea and delayed menarche despite hormone therapy: a longitudinal study". Fertil. Steril. 80 (2): 398–404. PMID 12909505.
- ↑ Warren MP, Miller KK, Olson WH, Grinspoon SK, Friedman AJ (2005). "Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in women with hypothalamic amenorrhea and osteopenia: an open-label extension of a double-blind, placebo-controlled study". Contraception. 72 (3): 206–11. doi:10.1016/j.contraception.2005.03.007. PMID 16102557.
- ↑ Gordon CM, Grace E, Emans SJ, Feldman HA, Goodman E, Becker KA, Rosen CJ, Gundberg CM, LeBoff MS (2002). "Effects of oral dehydroepiandrosterone on bone density in young women with anorexia nervosa: a randomized trial". J. Clin. Endocrinol. Metab. 87 (11): 4935–41. doi:10.1210/jc.2002-020545. PMID 12414853.
- ↑ Grinspoon S, Thomas L, Miller K, Herzog D, Klibanski A (2002). "Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa". J. Clin. Endocrinol. Metab. 87 (6): 2883–91. doi:10.1210/jcem.87.6.8574. PMID 12050268.
- ↑ Welt CK, Chan JL, Bullen J, Murphy R, Smith P, DePaoli AM, Karalis A, Mantzoros CS (2004). "Recombinant human leptin in women with hypothalamic amenorrhea". N. Engl. J. Med. 351 (10): 987–97. doi:10.1056/NEJMoa040388. PMID 15342807.
- ↑ Golden NH, Iglesias EA, Jacobson MS, Carey D, Meyer W, Schebendach J, Hertz S, Shenker IR (2005). "Alendronate for the treatment of osteopenia in anorexia nervosa: a randomized, double-blind, placebo-controlled trial". J. Clin. Endocrinol. Metab. 90 (6): 3179–85. doi:10.1210/jc.2004-1659. PMID 15784715.
- ↑ Viapiana O, Gatti D, Dalle Grave R, Todesco T, Rossini M, Braga V, Idolazzi L, Fracassi E, Adami S (2007). "Marked increases in bone mineral density and biochemical markers of bone turnover in patients with anorexia nervosa gaining weight". Bone. 40 (4): 1073–7. doi:10.1016/j.bone.2006.11.015. PMID 17240212.
- ↑ Dominguez J, Goodman L, Sen Gupta S, Mayer L, Etu SF, Walsh BT, Wang J, Pierson R, Warren MP (2007). "Treatment of anorexia nervosa is associated with increases in bone mineral density, and recovery is a biphasic process involving both nutrition and return of menses". Am. J. Clin. Nutr. 86 (1): 92–9. PMID 17616767.
- ↑ Fredericson M, Kent K (2005). "Normalization of bone density in a previously amenorrheic runner with osteoporosis". Med Sci Sports Exerc. 37 (9): 1481–6. PMID 16177598.