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There are dozens of medications containing combinations of estrogen and progestin. I am often confused by the bewildering proliferation of generic brand names used to describe the same estrogen-progestin (E-P) regimen. For example, the combination medication containing ethinyl estradiol 20 µg plus norethindrone acetate (NEA) 1 mg is available under at least 5 different names: Lo Estrin 1/20 (Warner Chilcot), Junel 1/20 (Teva Pharmaceuticals), Microgestin Fe 1/20 (Mayne Pharma), Gildess 1/20 (Qualitest Pharmaceuticals), and Larin 1/20 (Novast Laboratories). To reduce the confusion, it is often useful to select a single preferred estrogen and progestin and use the dose combinations that are available to treat a wide range of gynecology problems (TABLE). In this editorial I focus on using various dose combinations of ethinyl estradiol and NEA to treat 3 common gynecologic problems.
CASE 1 Polycystic ovary syndrome
A 19-year-old woman reports 4 spontaneous menses in the past year and bothersome facial hair and acne. Her total testosterone concentration is at the upper limit of normal (0.46 ng/mL) and her sex hormone binding globulin (SHBG) concentration is at the lower limit of normal (35 nM). For treatment of the patient’s menstrual disorder, what is an optimal E-P combination?
Prioritize the use of an estrogen-dominant medication
Based on the Rotterdam criteria this woman has polycystic ovary syndrome (PCOS).1 In women with PCOS, luteinizing hormone (LH) secretion is increased, stimulating excessive ovarian production of testosterone.2 In addition, many women with PCOS have decreased hepatic secretion of SHBG, a binding protein that prevents testosterone from entering cells, resulting in excessive bioavailable testosterone.3 The Endocrine Society recommends that women with PCOS who have menstrual dysfunction or hirsutism be treated initially with a combination E-P hormone medication.1 Combination E-P medications suppress pituitary secretion of LH, thereby reducing ovarian production of testosterone, and ethinyl estradiol increases hepatic secretion of SHBG, reducing bioavailable testosterone. These two goals are best accomplished with an oral E-P hormone medication containing ethinyl estradiol doses of 20 µg to 30 µg per pill. An E-P hormone medication containing pills with an ethinyl estradiol dose ≤ 10 µg-daily may stimulate less hepatic production of SHBG than a pill with an ethinyl estradiol dose of 20 µg or 30 µg daily.4,5 In addition, E-P pills containing levonorgestrel suppress SHBG hormone secretion compared with E-P pills with other progestins.6 Therefore, levonorgestrel-containing E-P pills should not be prioritized for use in women with PCOS because the estrogen-induced increase in SHBG will be blunted by levonorgestrel.
CASE 2 Moderate to severe pelvic pain caused by endometriosis
A 25-year-old woman (G0) with severe dysmenorrhea had a laparoscopy showing endometriosis lesions in the cul-de-sac and a peritoneal window near the left uterosacral ligament. Biopsy showed endometriosis. Postoperatively, the patient was treated with an E-P pill containing 30 µg ethinyl estradiol and 0.15 mg desogestrel per pill using a continuous-dosing protocol. During the year following the laparoscopy, her pelvic pain symptoms gradually increased until they became severe, preventing her from performing daily activities on multiple days per month. She was prescribed elagolix but her insurance did not approve the treatment. What alternative treatment would you prescribe?
Continue to: Use progestin-dominant pills to treat pelvic pain...
Use progestin-dominant pills to treat pelvic pain
Cellular activity in endometriosis lesions is stimulated by estradiol and inhibited by a high concentration of androgenic progestins or androgens. This simplified endocrine paradigm explains the effectiveness of hormonal treatments that suppress ovarian estradiol production, including leuprolide, elagolix, medroxyprogesterone acetate, and NEA. For the woman in the above case, I would advocate for elagolix treatment but, following the insurance denial of the prescription, an alternative treatment for moderate or severe pelvic pain caused by endometriosis would be a progestin-dominant hormone medication (for example, NEA 5 mg daily). Norethindrone acetate 5 mg daily may be associated with bothersome adverse effects including weight gain (16% of patients; mean weight gain, 3.1 kg), acne (10%), mood lability (9%), hot flashes (8%), depression (6%), scalp hair loss (4%), headache (4%), nausea (3%), and deepening of the voice (1%).7
I sometimes see women with moderate to severe pelvic pain caused by endometriosis being treated with norethindrone 0.35 mg daily. This dose of norethindrone is suboptimal for pain treatment because it does not reliably suppress ovarian production of estradiol. In addition, the cells in endometriosis lesions are often resistant to the effects of progesterone, requiring higher dosages to produce secretory or decidual changes. In most situations, I recommend against the use of norethindrone 0.35 mg daily for the treatment of pelvic pain caused by endometriosis.
Patients commonly ask if NEA 5 mg daily has contraceptive efficacy. Although it is not approved at this dosage by the US Food and Drug Administration as a contraceptive,8 norethindrone 0.35 mg daily is approved as a progestin-only contraceptive.9 Norethindrone acetate is rapidly and completely deacetylated to norethindrone and the disposition of oral NEA is indistinguishable from that of norethindrone (which is the FDA-approved dosage mentioned above). Since norethindrone 0.35 mg daily is approved as a contraceptive, it is highly likely that NEA 5 mg daily has contraceptive efficacy, especially if there is good adherence with the daily medication.
CASE 3 Perimenopausal AUB
A 45-year-old woman reports varying menstrual cycle lengths from 24 to 60 days with very heavy menses in some cycles. Pelvic ultrasonography shows no abnormality. Endometrial biopsy shows a proliferative endometrium. Her serum progesterone level, obtained 1 week before the onset of menses, is < 3 ng/mL. She has no past history of heavy menses, easy bruising, excessive bleeding with procedures, or a family history of bleeding problems. She also reports occasional hot flashes that wake her from sleep.
Use an estrogen step-down regimen to manage postmenopause transition
This patient is likely in the perimenopause transition, and the abnormal uterine bleeding (AUB) is caused, in part, by oligo- or anovulation. Perimenopausal women with AUB may have cycles characterized by above normal ovarian estradiol production and below normal progesterone production, or frank anovulation.10 Elevated ovarian estrogen and low progesterone production sets the stage for heavy bleeding in the perimenopause, regardless of the presence of uterine pathology such as fibroids.
For perimenopausal women, one option for treatment of AUB due to anovulation is to prescribe an estrogen step-down regimen. For the 45-year-old woman in this case, initiating treatment with an E-P pill containing ethinyl estradiol 10 µg and NEA 1 mg will likely control the AUB and her occasional hot flash.11 As the woman ages, the ethinyl estradiol dose can be decreased to pills containing 5 µg and then 2.5 µg, covering the transition into postmenopause. Once the woman is in the postmenopause, treatment with transdermal estradiol and oral micronized progesterone is an option to treat menopausal vasomotor symptoms.
Optimize estrogen and progestin treatment for your patients
Many gynecologic problems are effectively treated by estrogen and/or progestin steroids. The dose of estrogen and progestin should be tailored to the specific problem. For PCOS, the estrogen dose selected should be sufficient to safely stimulate hepatic SHBG production. For endometriosis, if a GnRH antagonist is not available to the patient, a high-dose progestin, such as NEA 5 mg, may be an effective treatment. During the perimenopause transition in a woman with AUB, a treatment plan using a sequential E-P step-down program might control symptoms and help smoothly glide the patient into the postmenopause. ●
- Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98:4565-4592. doi: 10.1210/jc.2013-2350.
- Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016;37:467-520. doi: 10.1210/er.2015-1104.
- Zhu JL, Chen Z, Feng WJ, et al. Sex hormone-binding globulin and polycystic ovary syndrome. Clin Chim Acta. 2019;499:142-148. doi: 10.1016/j.cca.2019.09.010.
- Oner G, Muderris II. A prospective randomized trial comparing low-dose ethinyl estradiol and drospirenone 24/4 combined oral contraceptive vs. ethinyl estradiol and drospirenone 21/7 combined oral contraceptive in the treatment of hirsutism. Contraception. 2011;84:508-511. doi: 10.1016/j.contraception.2011.03.002.
- Boyd RA, Zegarac EA, Posvar EL, et al. Minimal androgenic activity of a new oral contraceptive containing norethindrone acetate and graduated doses of ethinyl estradiol. Contraception. 2001;63:71-76. doi: 10.1016/s0010-7824(01)00179-2.
- Thorneycroft IH, Stanczyk FZ, Bradshaw KD, et al. Effect of low-dose oral contraceptives on androgenic markers and acne. Contraception. 1999;60:255-262. doi: 10.1016/s0010-7824(99)00093-1.
- Kaser DJ, Missmer SA, Berry KF, et al. Use of norethindrone acetate alone for postoperative suppression of endometriosis symptoms. J Pediatr Adolesc Gynecol. 2012;25:105-108. doi: 10.1016/j.jpag.2011.09.013.
- Aygestin [package insert]. Pomona, NY: Duramed Pharmaceuticals; 2007.
- Camila [package insert]. Greenville, NC; Mayne Pharma; 2018.
- Santoro N, Brown JR, Adel T, et al. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab. 1996;81:1495-1501. doi: 10.1210/jcem.81.4.8636357.
- Speroff L, Symons J, Kempfert N, et al; FemHrt Study Investigators. The effect of varying low-dose combinations of norethindrone acetate and ethinyl estradiol (Femhrt) on the frequency and intensity of vasomotor symptoms. Menopause. 2000;7:383-390. doi: 10.1097/00042192-200011000-00003.
Robert L. Barbieri, MD
Chair Emeritus, Department of Obstetrics and Gynecology
Interim Chief, Obstetrics
Brigham and Women’s Hospital
Kate Macy Ladd Distinguished Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School
Boston, Massachusetts
Dr. Barbieri reports no financial relationships relevant to this article.
Robert L. Barbieri, MD
Chair Emeritus, Department of Obstetrics and Gynecology
Interim Chief, Obstetrics
Brigham and Women’s Hospital
Kate Macy Ladd Distinguished Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School
Boston, Massachusetts
Dr. Barbieri reports no financial relationships relevant to this article.
Robert L. Barbieri, MD
Chair Emeritus, Department of Obstetrics and Gynecology
Interim Chief, Obstetrics
Brigham and Women’s Hospital
Kate Macy Ladd Distinguished Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School
Boston, Massachusetts
Dr. Barbieri reports no financial relationships relevant to this article.
There are dozens of medications containing combinations of estrogen and progestin. I am often confused by the bewildering proliferation of generic brand names used to describe the same estrogen-progestin (E-P) regimen. For example, the combination medication containing ethinyl estradiol 20 µg plus norethindrone acetate (NEA) 1 mg is available under at least 5 different names: Lo Estrin 1/20 (Warner Chilcot), Junel 1/20 (Teva Pharmaceuticals), Microgestin Fe 1/20 (Mayne Pharma), Gildess 1/20 (Qualitest Pharmaceuticals), and Larin 1/20 (Novast Laboratories). To reduce the confusion, it is often useful to select a single preferred estrogen and progestin and use the dose combinations that are available to treat a wide range of gynecology problems (TABLE). In this editorial I focus on using various dose combinations of ethinyl estradiol and NEA to treat 3 common gynecologic problems.
CASE 1 Polycystic ovary syndrome
A 19-year-old woman reports 4 spontaneous menses in the past year and bothersome facial hair and acne. Her total testosterone concentration is at the upper limit of normal (0.46 ng/mL) and her sex hormone binding globulin (SHBG) concentration is at the lower limit of normal (35 nM). For treatment of the patient’s menstrual disorder, what is an optimal E-P combination?
Prioritize the use of an estrogen-dominant medication
Based on the Rotterdam criteria this woman has polycystic ovary syndrome (PCOS).1 In women with PCOS, luteinizing hormone (LH) secretion is increased, stimulating excessive ovarian production of testosterone.2 In addition, many women with PCOS have decreased hepatic secretion of SHBG, a binding protein that prevents testosterone from entering cells, resulting in excessive bioavailable testosterone.3 The Endocrine Society recommends that women with PCOS who have menstrual dysfunction or hirsutism be treated initially with a combination E-P hormone medication.1 Combination E-P medications suppress pituitary secretion of LH, thereby reducing ovarian production of testosterone, and ethinyl estradiol increases hepatic secretion of SHBG, reducing bioavailable testosterone. These two goals are best accomplished with an oral E-P hormone medication containing ethinyl estradiol doses of 20 µg to 30 µg per pill. An E-P hormone medication containing pills with an ethinyl estradiol dose ≤ 10 µg-daily may stimulate less hepatic production of SHBG than a pill with an ethinyl estradiol dose of 20 µg or 30 µg daily.4,5 In addition, E-P pills containing levonorgestrel suppress SHBG hormone secretion compared with E-P pills with other progestins.6 Therefore, levonorgestrel-containing E-P pills should not be prioritized for use in women with PCOS because the estrogen-induced increase in SHBG will be blunted by levonorgestrel.
CASE 2 Moderate to severe pelvic pain caused by endometriosis
A 25-year-old woman (G0) with severe dysmenorrhea had a laparoscopy showing endometriosis lesions in the cul-de-sac and a peritoneal window near the left uterosacral ligament. Biopsy showed endometriosis. Postoperatively, the patient was treated with an E-P pill containing 30 µg ethinyl estradiol and 0.15 mg desogestrel per pill using a continuous-dosing protocol. During the year following the laparoscopy, her pelvic pain symptoms gradually increased until they became severe, preventing her from performing daily activities on multiple days per month. She was prescribed elagolix but her insurance did not approve the treatment. What alternative treatment would you prescribe?
Continue to: Use progestin-dominant pills to treat pelvic pain...
Use progestin-dominant pills to treat pelvic pain
Cellular activity in endometriosis lesions is stimulated by estradiol and inhibited by a high concentration of androgenic progestins or androgens. This simplified endocrine paradigm explains the effectiveness of hormonal treatments that suppress ovarian estradiol production, including leuprolide, elagolix, medroxyprogesterone acetate, and NEA. For the woman in the above case, I would advocate for elagolix treatment but, following the insurance denial of the prescription, an alternative treatment for moderate or severe pelvic pain caused by endometriosis would be a progestin-dominant hormone medication (for example, NEA 5 mg daily). Norethindrone acetate 5 mg daily may be associated with bothersome adverse effects including weight gain (16% of patients; mean weight gain, 3.1 kg), acne (10%), mood lability (9%), hot flashes (8%), depression (6%), scalp hair loss (4%), headache (4%), nausea (3%), and deepening of the voice (1%).7
I sometimes see women with moderate to severe pelvic pain caused by endometriosis being treated with norethindrone 0.35 mg daily. This dose of norethindrone is suboptimal for pain treatment because it does not reliably suppress ovarian production of estradiol. In addition, the cells in endometriosis lesions are often resistant to the effects of progesterone, requiring higher dosages to produce secretory or decidual changes. In most situations, I recommend against the use of norethindrone 0.35 mg daily for the treatment of pelvic pain caused by endometriosis.
Patients commonly ask if NEA 5 mg daily has contraceptive efficacy. Although it is not approved at this dosage by the US Food and Drug Administration as a contraceptive,8 norethindrone 0.35 mg daily is approved as a progestin-only contraceptive.9 Norethindrone acetate is rapidly and completely deacetylated to norethindrone and the disposition of oral NEA is indistinguishable from that of norethindrone (which is the FDA-approved dosage mentioned above). Since norethindrone 0.35 mg daily is approved as a contraceptive, it is highly likely that NEA 5 mg daily has contraceptive efficacy, especially if there is good adherence with the daily medication.
CASE 3 Perimenopausal AUB
A 45-year-old woman reports varying menstrual cycle lengths from 24 to 60 days with very heavy menses in some cycles. Pelvic ultrasonography shows no abnormality. Endometrial biopsy shows a proliferative endometrium. Her serum progesterone level, obtained 1 week before the onset of menses, is < 3 ng/mL. She has no past history of heavy menses, easy bruising, excessive bleeding with procedures, or a family history of bleeding problems. She also reports occasional hot flashes that wake her from sleep.
Use an estrogen step-down regimen to manage postmenopause transition
This patient is likely in the perimenopause transition, and the abnormal uterine bleeding (AUB) is caused, in part, by oligo- or anovulation. Perimenopausal women with AUB may have cycles characterized by above normal ovarian estradiol production and below normal progesterone production, or frank anovulation.10 Elevated ovarian estrogen and low progesterone production sets the stage for heavy bleeding in the perimenopause, regardless of the presence of uterine pathology such as fibroids.
For perimenopausal women, one option for treatment of AUB due to anovulation is to prescribe an estrogen step-down regimen. For the 45-year-old woman in this case, initiating treatment with an E-P pill containing ethinyl estradiol 10 µg and NEA 1 mg will likely control the AUB and her occasional hot flash.11 As the woman ages, the ethinyl estradiol dose can be decreased to pills containing 5 µg and then 2.5 µg, covering the transition into postmenopause. Once the woman is in the postmenopause, treatment with transdermal estradiol and oral micronized progesterone is an option to treat menopausal vasomotor symptoms.
Optimize estrogen and progestin treatment for your patients
Many gynecologic problems are effectively treated by estrogen and/or progestin steroids. The dose of estrogen and progestin should be tailored to the specific problem. For PCOS, the estrogen dose selected should be sufficient to safely stimulate hepatic SHBG production. For endometriosis, if a GnRH antagonist is not available to the patient, a high-dose progestin, such as NEA 5 mg, may be an effective treatment. During the perimenopause transition in a woman with AUB, a treatment plan using a sequential E-P step-down program might control symptoms and help smoothly glide the patient into the postmenopause. ●
There are dozens of medications containing combinations of estrogen and progestin. I am often confused by the bewildering proliferation of generic brand names used to describe the same estrogen-progestin (E-P) regimen. For example, the combination medication containing ethinyl estradiol 20 µg plus norethindrone acetate (NEA) 1 mg is available under at least 5 different names: Lo Estrin 1/20 (Warner Chilcot), Junel 1/20 (Teva Pharmaceuticals), Microgestin Fe 1/20 (Mayne Pharma), Gildess 1/20 (Qualitest Pharmaceuticals), and Larin 1/20 (Novast Laboratories). To reduce the confusion, it is often useful to select a single preferred estrogen and progestin and use the dose combinations that are available to treat a wide range of gynecology problems (TABLE). In this editorial I focus on using various dose combinations of ethinyl estradiol and NEA to treat 3 common gynecologic problems.
CASE 1 Polycystic ovary syndrome
A 19-year-old woman reports 4 spontaneous menses in the past year and bothersome facial hair and acne. Her total testosterone concentration is at the upper limit of normal (0.46 ng/mL) and her sex hormone binding globulin (SHBG) concentration is at the lower limit of normal (35 nM). For treatment of the patient’s menstrual disorder, what is an optimal E-P combination?
Prioritize the use of an estrogen-dominant medication
Based on the Rotterdam criteria this woman has polycystic ovary syndrome (PCOS).1 In women with PCOS, luteinizing hormone (LH) secretion is increased, stimulating excessive ovarian production of testosterone.2 In addition, many women with PCOS have decreased hepatic secretion of SHBG, a binding protein that prevents testosterone from entering cells, resulting in excessive bioavailable testosterone.3 The Endocrine Society recommends that women with PCOS who have menstrual dysfunction or hirsutism be treated initially with a combination E-P hormone medication.1 Combination E-P medications suppress pituitary secretion of LH, thereby reducing ovarian production of testosterone, and ethinyl estradiol increases hepatic secretion of SHBG, reducing bioavailable testosterone. These two goals are best accomplished with an oral E-P hormone medication containing ethinyl estradiol doses of 20 µg to 30 µg per pill. An E-P hormone medication containing pills with an ethinyl estradiol dose ≤ 10 µg-daily may stimulate less hepatic production of SHBG than a pill with an ethinyl estradiol dose of 20 µg or 30 µg daily.4,5 In addition, E-P pills containing levonorgestrel suppress SHBG hormone secretion compared with E-P pills with other progestins.6 Therefore, levonorgestrel-containing E-P pills should not be prioritized for use in women with PCOS because the estrogen-induced increase in SHBG will be blunted by levonorgestrel.
CASE 2 Moderate to severe pelvic pain caused by endometriosis
A 25-year-old woman (G0) with severe dysmenorrhea had a laparoscopy showing endometriosis lesions in the cul-de-sac and a peritoneal window near the left uterosacral ligament. Biopsy showed endometriosis. Postoperatively, the patient was treated with an E-P pill containing 30 µg ethinyl estradiol and 0.15 mg desogestrel per pill using a continuous-dosing protocol. During the year following the laparoscopy, her pelvic pain symptoms gradually increased until they became severe, preventing her from performing daily activities on multiple days per month. She was prescribed elagolix but her insurance did not approve the treatment. What alternative treatment would you prescribe?
Continue to: Use progestin-dominant pills to treat pelvic pain...
Use progestin-dominant pills to treat pelvic pain
Cellular activity in endometriosis lesions is stimulated by estradiol and inhibited by a high concentration of androgenic progestins or androgens. This simplified endocrine paradigm explains the effectiveness of hormonal treatments that suppress ovarian estradiol production, including leuprolide, elagolix, medroxyprogesterone acetate, and NEA. For the woman in the above case, I would advocate for elagolix treatment but, following the insurance denial of the prescription, an alternative treatment for moderate or severe pelvic pain caused by endometriosis would be a progestin-dominant hormone medication (for example, NEA 5 mg daily). Norethindrone acetate 5 mg daily may be associated with bothersome adverse effects including weight gain (16% of patients; mean weight gain, 3.1 kg), acne (10%), mood lability (9%), hot flashes (8%), depression (6%), scalp hair loss (4%), headache (4%), nausea (3%), and deepening of the voice (1%).7
I sometimes see women with moderate to severe pelvic pain caused by endometriosis being treated with norethindrone 0.35 mg daily. This dose of norethindrone is suboptimal for pain treatment because it does not reliably suppress ovarian production of estradiol. In addition, the cells in endometriosis lesions are often resistant to the effects of progesterone, requiring higher dosages to produce secretory or decidual changes. In most situations, I recommend against the use of norethindrone 0.35 mg daily for the treatment of pelvic pain caused by endometriosis.
Patients commonly ask if NEA 5 mg daily has contraceptive efficacy. Although it is not approved at this dosage by the US Food and Drug Administration as a contraceptive,8 norethindrone 0.35 mg daily is approved as a progestin-only contraceptive.9 Norethindrone acetate is rapidly and completely deacetylated to norethindrone and the disposition of oral NEA is indistinguishable from that of norethindrone (which is the FDA-approved dosage mentioned above). Since norethindrone 0.35 mg daily is approved as a contraceptive, it is highly likely that NEA 5 mg daily has contraceptive efficacy, especially if there is good adherence with the daily medication.
CASE 3 Perimenopausal AUB
A 45-year-old woman reports varying menstrual cycle lengths from 24 to 60 days with very heavy menses in some cycles. Pelvic ultrasonography shows no abnormality. Endometrial biopsy shows a proliferative endometrium. Her serum progesterone level, obtained 1 week before the onset of menses, is < 3 ng/mL. She has no past history of heavy menses, easy bruising, excessive bleeding with procedures, or a family history of bleeding problems. She also reports occasional hot flashes that wake her from sleep.
Use an estrogen step-down regimen to manage postmenopause transition
This patient is likely in the perimenopause transition, and the abnormal uterine bleeding (AUB) is caused, in part, by oligo- or anovulation. Perimenopausal women with AUB may have cycles characterized by above normal ovarian estradiol production and below normal progesterone production, or frank anovulation.10 Elevated ovarian estrogen and low progesterone production sets the stage for heavy bleeding in the perimenopause, regardless of the presence of uterine pathology such as fibroids.
For perimenopausal women, one option for treatment of AUB due to anovulation is to prescribe an estrogen step-down regimen. For the 45-year-old woman in this case, initiating treatment with an E-P pill containing ethinyl estradiol 10 µg and NEA 1 mg will likely control the AUB and her occasional hot flash.11 As the woman ages, the ethinyl estradiol dose can be decreased to pills containing 5 µg and then 2.5 µg, covering the transition into postmenopause. Once the woman is in the postmenopause, treatment with transdermal estradiol and oral micronized progesterone is an option to treat menopausal vasomotor symptoms.
Optimize estrogen and progestin treatment for your patients
Many gynecologic problems are effectively treated by estrogen and/or progestin steroids. The dose of estrogen and progestin should be tailored to the specific problem. For PCOS, the estrogen dose selected should be sufficient to safely stimulate hepatic SHBG production. For endometriosis, if a GnRH antagonist is not available to the patient, a high-dose progestin, such as NEA 5 mg, may be an effective treatment. During the perimenopause transition in a woman with AUB, a treatment plan using a sequential E-P step-down program might control symptoms and help smoothly glide the patient into the postmenopause. ●
- Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98:4565-4592. doi: 10.1210/jc.2013-2350.
- Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016;37:467-520. doi: 10.1210/er.2015-1104.
- Zhu JL, Chen Z, Feng WJ, et al. Sex hormone-binding globulin and polycystic ovary syndrome. Clin Chim Acta. 2019;499:142-148. doi: 10.1016/j.cca.2019.09.010.
- Oner G, Muderris II. A prospective randomized trial comparing low-dose ethinyl estradiol and drospirenone 24/4 combined oral contraceptive vs. ethinyl estradiol and drospirenone 21/7 combined oral contraceptive in the treatment of hirsutism. Contraception. 2011;84:508-511. doi: 10.1016/j.contraception.2011.03.002.
- Boyd RA, Zegarac EA, Posvar EL, et al. Minimal androgenic activity of a new oral contraceptive containing norethindrone acetate and graduated doses of ethinyl estradiol. Contraception. 2001;63:71-76. doi: 10.1016/s0010-7824(01)00179-2.
- Thorneycroft IH, Stanczyk FZ, Bradshaw KD, et al. Effect of low-dose oral contraceptives on androgenic markers and acne. Contraception. 1999;60:255-262. doi: 10.1016/s0010-7824(99)00093-1.
- Kaser DJ, Missmer SA, Berry KF, et al. Use of norethindrone acetate alone for postoperative suppression of endometriosis symptoms. J Pediatr Adolesc Gynecol. 2012;25:105-108. doi: 10.1016/j.jpag.2011.09.013.
- Aygestin [package insert]. Pomona, NY: Duramed Pharmaceuticals; 2007.
- Camila [package insert]. Greenville, NC; Mayne Pharma; 2018.
- Santoro N, Brown JR, Adel T, et al. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab. 1996;81:1495-1501. doi: 10.1210/jcem.81.4.8636357.
- Speroff L, Symons J, Kempfert N, et al; FemHrt Study Investigators. The effect of varying low-dose combinations of norethindrone acetate and ethinyl estradiol (Femhrt) on the frequency and intensity of vasomotor symptoms. Menopause. 2000;7:383-390. doi: 10.1097/00042192-200011000-00003.
- Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98:4565-4592. doi: 10.1210/jc.2013-2350.
- Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016;37:467-520. doi: 10.1210/er.2015-1104.
- Zhu JL, Chen Z, Feng WJ, et al. Sex hormone-binding globulin and polycystic ovary syndrome. Clin Chim Acta. 2019;499:142-148. doi: 10.1016/j.cca.2019.09.010.
- Oner G, Muderris II. A prospective randomized trial comparing low-dose ethinyl estradiol and drospirenone 24/4 combined oral contraceptive vs. ethinyl estradiol and drospirenone 21/7 combined oral contraceptive in the treatment of hirsutism. Contraception. 2011;84:508-511. doi: 10.1016/j.contraception.2011.03.002.
- Boyd RA, Zegarac EA, Posvar EL, et al. Minimal androgenic activity of a new oral contraceptive containing norethindrone acetate and graduated doses of ethinyl estradiol. Contraception. 2001;63:71-76. doi: 10.1016/s0010-7824(01)00179-2.
- Thorneycroft IH, Stanczyk FZ, Bradshaw KD, et al. Effect of low-dose oral contraceptives on androgenic markers and acne. Contraception. 1999;60:255-262. doi: 10.1016/s0010-7824(99)00093-1.
- Kaser DJ, Missmer SA, Berry KF, et al. Use of norethindrone acetate alone for postoperative suppression of endometriosis symptoms. J Pediatr Adolesc Gynecol. 2012;25:105-108. doi: 10.1016/j.jpag.2011.09.013.
- Aygestin [package insert]. Pomona, NY: Duramed Pharmaceuticals; 2007.
- Camila [package insert]. Greenville, NC; Mayne Pharma; 2018.
- Santoro N, Brown JR, Adel T, et al. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab. 1996;81:1495-1501. doi: 10.1210/jcem.81.4.8636357.
- Speroff L, Symons J, Kempfert N, et al; FemHrt Study Investigators. The effect of varying low-dose combinations of norethindrone acetate and ethinyl estradiol (Femhrt) on the frequency and intensity of vasomotor symptoms. Menopause. 2000;7:383-390. doi: 10.1097/00042192-200011000-00003.
