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]
| Type of amenorrhea | Medicine | Dosage | Treatment duration | Bone mineral density (BMD) site | Outcome | |
|---|---|---|---|---|---|---|
| Exercise-associated functional amenorrhea |
Ethinyl estradiol | 0.035 mg | 12 months | Lumbar spine and femoral neck | Increased BMD in all sites[2] | |
| Norethindrone Medroxyprogesterone |
0.5-1.0 mg 10 mg | |||||
| Ethinyl estradiol | 0.03 or 0.02 mg | 12 months | Lumbar spine | Increased BMD in all sites[3] | ||
| Desogestrel | 0.15 mg | |||||
| Ethinyl estradiol | 0.030 mg | 10 months | Lumbar spine and legs | Increase BMD in lumbar spine not in legs[4] | ||
| Levonorgestrel | 0.150 mg | |||||
| Ethinyl estradiol | 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 | |||||
| Anorexia-associated functional amenorrhea |
Ethinyl estradiol | 0.020–0.035 mg | 12 months | Lumbar spine and femoral neck | No change BMD in any sites[10] | |
| Norgestimate Norgestrel Norethindrone acetate Levonorgestrel |
0.180–0.250 mg 0.5 mg 0.5-1.0 mg - | |||||
| Ethinyl estradiol | 0.05 mg | 12 months | Lumbar spine | No change BMD[11] | ||
| Norgestrel | 0.5 mg | |||||
| Premarin | 0.625 mg | 18 months | Lumbar spine | No change BMD[12] | ||
| Provera | 5 mg | |||||
| Ethinyl estradiol | 0.035 mg | |||||
| Premarin | 0.3–0.625 mg daily | 4.3 years | Lumbar spine and femoral neck | Increased BMD in all sites[13] | ||
| Ethinyl estradiol | 0.020 mg | 12 months | Lumbar spine and femoral neck | No change BMD in any sites[14] | ||
| Levonorgestrel | 0.1 mg | |||||
| Dihydroepiandrostendion (DHEA) | 50 mg daily | |||||
| Recombinant IGF-1 | 30 mg/kg twice daily | 9 months | Lumbar spine, femoral neck, and radius | No change BMD in any sites[15] | ||
| Ethinyl estradiol | 0.035 mg | |||||
| Norethindrone | 0.4 mg | |||||
| Ethinyl estradiol | 0.035 mg | 13 cycles | Lumbar spine and femoral neck | No significant change BMD in any sites[16] | ||
| Norgestimate | 0.180–0.250 mg | |||||
Androgen therapy
- Recent studies have shown that androgen therapy in the dose of 50, 100, or 200 mg of micronized DHEA daily may increase bone mineral density (BMD), and prevent osteoporotic fracture. However, there is no established long term study to prove this effect.[14]
Recombinant insulin like growth factor 1 (IGF-1)
- 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) prevents fracture in hypothalamic amenorrhea (due to anorexia nervosa) by increasing bone mineral density (BMD).[15]
Recombinant leptin
- Recent studies have shown that administering recombinant leptin (0.08 mg/kg) subcutaneous daily for 2–3 months can lead to an increase in bone formation markers; and also decrease fracture risk through secondary prevention.[17]
Bisphosphonates
- In adolescent women with anorexia-induced amenorrhea, alendronate (10 mg) with calcium (1200 mg) and vitamin D (400 IU) for a year has been associated with significant improvement in bone loss. Therefore, bisphosphonates can be used as secondary prevention.[18]
- Doses of bisphosphonates for secondary prevention of functional amenorrhea are as follows:
| Medicine | Dose | Treatment duration | Bone mineral density (BMD) site | Outcome |
|---|---|---|---|---|
| Etidronate | 200 mg daily | 3 months | Tibial midshaft | Non-significant increase in BMD in all sites[19] |
| Calcium | 600 mg daily | |||
| Vitamin D | 1 μg daily | |||
| Risedronate | 5 mg | 9 months | Lumbar spine and femoral neck | Increase BMD in lumbar spine not in femoral neck[20] |
| Calcium | 1500 mg | |||
| Vitamin D | 400 IU | |||
| Alendronate | 10 mg | 12 months | Lumbar spine and femoral neck | Non-significant increase in BMD in all sites[21] |
| Calcium | 1200 mg | |||
| Vitamin D | 400 IU |
Increasing calorie intake
- Increasing daily calorie intake and weight gain in women with anorexia- or exercise-induced amenorrhea can increase bone mineral density (BMD) and decrease long term complications associated with amenorrhea such as osteoporosis and fracture.[22][23][24]
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.
- ↑ Golden NH, Lanzkowsky L, Schebendach J, Palestro CJ, Jacobson MS, Shenker IR (2002). "The effect of estrogen-progestin treatment on bone mineral density in anorexia nervosa". J Pediatr Adolesc Gynecol. 15 (3): 135–43. PMID 12106749.
- ↑ Muñoz MT, Morandé G, García-Centenera JA, Hervás F, Pozo J, Argente J (2002). "The effects of estrogen administration on bone mineral density in adolescents with anorexia nervosa". Eur. J. Endocrinol. 146 (1): 45–50. PMID 11751066.
- ↑ Klibanski A, Biller BM, Schoenfeld DA, Herzog DB, Saxe VC (1995). "The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa". J. Clin. Endocrinol. Metab. 80 (3): 898–904. doi:10.1210/jcem.80.3.7883849. PMID 7883849.
- ↑ Karlsson MK, Weigall SJ, Duan Y, Seeman E (2000). "Bone size and volumetric density in women with anorexia nervosa receiving estrogen replacement therapy and in women recovered from anorexia nervosa". J. Clin. Endocrinol. Metab. 85 (9): 3177–82. doi:10.1210/jcem.85.9.6796. PMID 10999805.
- ↑ 14.0 14.1 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.
- ↑ 15.0 15.1 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.
- ↑ Strokosch GR, Friedman AJ, Wu SC, Kamin M (2006). "Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in adolescent females with anorexia nervosa: a double-blind, placebo-controlled study". J Adolesc Health. 39 (6): 819–27. doi:10.1016/j.jadohealth.2006.09.010. PMID 17116511.
- ↑ 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.
- ↑ Nakahara T, Nagai N, Tanaka M, Muranaga T, Kojima S, Nozoe S, Naruo T (2006). "The effects of bone therapy on tibial bone loss in young women with anorexia nervosa". Int J Eat Disord. 39 (1): 20–6. doi:10.1002/eat.20197. PMID 16231362.
- ↑ Miller KK, Grieco KA, Mulder J, Grinspoon S, Mickley D, Yehezkel R, Herzog DB, Klibanski A (2004). "Effects of risedronate on bone density in anorexia nervosa". J. Clin. Endocrinol. Metab. 89 (8): 3903–6. doi:10.1210/jc.2003-031885. PMID 15292325.
- ↑ 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.