Clinical Review

Focus on menopause

OBG Manag. 2022 December;34(12):18-22, 24-25, 37, 47 | 10.12788/obgm.0246

Q&A with Jan Shifren, MD, and Genevieve Neal-Perry, MD, PhD

The annual meeting of The North American Menopause Society featured several presentations aimed at educating attendees on hormone therapy, an on-the-horizon nonhormonal option for hot flashes, and multiethnic differences in the menopause experience

PDF Download

References

Canonico M, Oger E, Plu-Bureau G, et al; Estrogen and Thromboembolism Risk (ESTHER) Study Group. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation. 2007;115:840-845. doi: 10.1161/CIRCULATIONAHA.106.642280.
Liu B, Beral V, Balkwill A, et al; Million Women Study Collaborators. Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study. BMJ. 2008;337:a386. doi: 10.1136/bmj.a386.
Renoux C, Dell’aniello S, Garbe E, et al. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ. 2010;340:c2519. doi: 10.1136/bmj. c2519.
Chlebowski RT, Anderson GL, Aragaki AK, et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women’s Health Initiative randomized clinical trials. JAMA. 2020;324:369-380. doi: 10.1001/jama.2020.9482.
Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297:1465-1477. doi: 10.1001/jama.297.13.1465.
Woods NF, Mitchell ES. Symptoms during the perimenopause: prevlance, severity, trajectory, and significance in women’s lives. Am J Med. 2005;118 suppl 12B:14-24. doi: 10.1016/j. amjmed.2005.09.031.
Gold EB, Block G, Crawford S, et al. Lifestyle and demographic factors in relation to vasomotor symptoms: baseline results from the Study of Women’s Health Across the Nation. Am J Epidemiol. 2004;159:1189-1199. doi: 10.1093/aje/kwh168.
Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med. 2015;175:531-539. doi: 10.1001/ jamainternmed.2014.8093.
Abel TW, Rance NE. Stereologic study of the hypothalamic infundibular nucleus in young and older women. J Comp Neurol. 2000;424:679-688. doi: 10.1002/1096-9861 (20000904)424:4<679::aid-cne9>3.0.co;2-l.
Neal-Perry G. A phase 3, randomized, placebo-controlled, double-blind study to investigate the long-term safety and tolerability of fezolinetant in women seeking treatment for vasomotor symptoms associated with menopause (SKYLIGHT 4) – Abstract S-11. Paper presented at ENDO 2022. June 11, 2022.
Crandall CJ, Diamant AL, Maglione M, et al. Genetic variation and hot flashes: a systematic review. J Clin Endocrinol Metab. 2020;105:e4907-e4957. doi: 10.1210/clinem/dgaa536.

OBG Management caught up with Drs. Jan Shifren and Genevieve Neal-Perry while they were attending the annual meeting of The North American Menopause Society (NAMS), held October 12-15, 2022, in Atlanta, Georgia. Dr. Shifren presented on the “Ins and Outs of Hormone Therapy,” while Dr. Neal-Perry focused on “Menopause Physiology.”

Evaluating symptomatic patients for appropriate hormone therapy

OBG Management: In your presentation to the group at the NAMS meeting, you described a 51-year-old patient with the principal symptoms of frequent hot flashes and night sweats, sleep disruption, fatigue, irritability, vaginal dryness, and dyspareunia. As she reported already trying several lifestyle modification approaches, what are your questions for her to determine whether hormone therapy (HT), systemic or low-dose vaginal, is advisable?

Jan Shifren, MD: As with every patient, you need to begin with a thorough history and confirm her physical exam is up to date. If there are concerns related to genitourinary symptoms of menopause (GSM), then a pelvic exam is indicated. This patient is a healthy menopausal woman with bothersome hot flashes, night sweats, and vaginal dryness. Sleep disruption from night sweats is likely the cause of her fatigue and irritability, and her dyspareunia due to atrophic vulvovaginal changes. The principal indication for systemic HT is bothersome vasomotor symptoms (VMS), and a healthy woman who is under age 60 or within 10 years of the onset of menopause is generally a very good candidate for hormones. For this healthy 51-year-old with bothersome VMS unresponsive to lifestyle modification, the benefits of HT should outweigh potential risks. As low-dose vaginal estrogen therapy is minimally absorbed and very safe, this would be recommended instead of systemic HT if her only menopause symptoms were vaginal dryness and dyspareunia.

HT types and formulations

OBG Management: For this patient, low-dose vaginal estrogen is appropriate. In general, how do you decide on recommendations for combination therapy or estrogen only, and what formulations and dosages do you recommend?

Dr. Shifren: Any woman with a uterus needs to take a progestogen together with estrogen to protect her uterus from estrogen-induced endometrial overgrowth. With low dose vaginal estrogen therapy, however, concurrent progestogen is not needed.

Continue to: Estrogen options...

References

Canonico M, Oger E, Plu-Bureau G, et al; Estrogen and Thromboembolism Risk (ESTHER) Study Group. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation. 2007;115:840-845. doi: 10.1161/CIRCULATIONAHA.106.642280.
Liu B, Beral V, Balkwill A, et al; Million Women Study Collaborators. Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study. BMJ. 2008;337:a386. doi: 10.1136/bmj.a386.
Renoux C, Dell’aniello S, Garbe E, et al. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ. 2010;340:c2519. doi: 10.1136/bmj. c2519.
Chlebowski RT, Anderson GL, Aragaki AK, et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women’s Health Initiative randomized clinical trials. JAMA. 2020;324:369-380. doi: 10.1001/jama.2020.9482.
Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297:1465-1477. doi: 10.1001/jama.297.13.1465.
Woods NF, Mitchell ES. Symptoms during the perimenopause: prevlance, severity, trajectory, and significance in women’s lives. Am J Med. 2005;118 suppl 12B:14-24. doi: 10.1016/j. amjmed.2005.09.031.
Gold EB, Block G, Crawford S, et al. Lifestyle and demographic factors in relation to vasomotor symptoms: baseline results from the Study of Women’s Health Across the Nation. Am J Epidemiol. 2004;159:1189-1199. doi: 10.1093/aje/kwh168.
Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med. 2015;175:531-539. doi: 10.1001/ jamainternmed.2014.8093.
Abel TW, Rance NE. Stereologic study of the hypothalamic infundibular nucleus in young and older women. J Comp Neurol. 2000;424:679-688. doi: 10.1002/1096-9861 (20000904)424:4<679::aid-cne9>3.0.co;2-l.
Neal-Perry G. A phase 3, randomized, placebo-controlled, double-blind study to investigate the long-term safety and tolerability of fezolinetant in women seeking treatment for vasomotor symptoms associated with menopause (SKYLIGHT 4) – Abstract S-11. Paper presented at ENDO 2022. June 11, 2022.
Crandall CJ, Diamant AL, Maglione M, et al. Genetic variation and hot flashes: a systematic review. J Clin Endocrinol Metab. 2020;105:e4907-e4957. doi: 10.1210/clinem/dgaa536.

Focus on menopause

References

Evaluating symptomatic patients for appropriate hormone therapy

HT types and formulations

OBG Management: For this patient, low-dose vaginal estrogen is appropriate. In general, how do you decide on recommendations for combination therapy or estrogen only, and what formulations and dosages do you recommend?

Pages

Recommended Reading