Commentary

A few questions about the new multiphasic OC…Reactions to "2 HPV vaccines, 7 questions that you need answered"


 


IN THE NEWS, NOW ON THE SHELF: A NOVEL ESTRADIOL BASED OC
ROBERT L. BARBIERI, MD (EDITORIAL; SEPTEMBER 2010)

A few questions about the new multiphasic OC

Having read Dr. Barbieri’s September editorial on the recently approved Natazia oral contraceptive (OC), I have several concerns:

  • A common complaint among women using an OC is early breast soreness, which has been attributed to the week-long hormone-free interval followed by a sudden increase in estrogen when active pills are resumed. Estrostep was developed years ago to address this issue by starting with a low dose of estrogen and gradually increasing the level of ethinyl estradiol to stabilize the endometrium. With Natazia, a starting dose of 3 mg of estradiol would seem to be rather large, with the potential for “early-pack” breast soreness, a common reason for discontinuing an OC.
  • The half-life of estradiol is very short. When micronized estradiol is given for menopausal symptoms, sometimes a twice-daily dosing pattern is required to smooth out the peaks and valleys of blood levels and minimize the bottoming out of the estrogen level. How does Natazia address this issue?
  • Early triphasic (progestin-phasing) pills are notorious for their association with breakthrough bleeding due to the step up in progestin. How does the breakthrough-bleeding rate of Natazia compare with that of other triphasic (progestin) pills and monophasic pills?
  • Why are there two estrogen-free days at the end of the Natazia pack? Women who have menstrual migraines often benefit from a low dosage of estrogen during the entire menstrual placebo week. In the case of Natazia, why not have a low dosage of estradiol for the entire menstrual week?

Jeffrey Musson, MD
Racine, Wisc

Dr. Barbieri responds:
Effects of Natazia are best viewed in comparison with an EE-LNG pill

Dr. Musson raises many important clinical issues concerning the estradiol valerate–dienogest contraceptive, Natazia. From my perspective, his clinical questions are best addressed by reviewing the data from the head-to-head randomized trial of Natazia versus a standard, monophasic 21/7, ethinyl estradiol (20 μg) plus levonorgestrel (100 μg) (EE-LNG) contraceptive.1 Some of the clinical highlights of this study:

  • Natazia treatment was associated with significantly fewer scheduled (withdrawal) bleeding days than the monophasic EE-LNG pill.
  • Natazia and the monophasic EELNG pill had a similar number of unscheduled (breakthrough or intracycle) bleeding days.
  • Amenorrhea was reported by 15% of the women taking Natazia and 5% of the women taking a monophasic EE-LNG pill.
  • Breast pain was reported by 3.3% of the women taking Natazia and 1.0% of the women taking the monophasic EE-LNG pill.

Estradiol has a half-life of about 160 minutes.2 Estradiol valerate is metabolized to estradiol, estrone, and estrone sulfate. The pools of estradiol valerate, estrone, and estrone sulfate help to stabilize the estradiol levels, through interconversion. The average concentration of estradiol in a user of Natazia is about 50 pg/mL, which is similar to the relatively modest estradiol concentrations observed in the early follicular phase.

I appreciate Dr. Musson’s help in further characterizing the effects of Natazia in clinical practice.



2 HPV VACCINES, 7 QUESTIONS THAT YOU NEED ANSWERED
EXPERT PANEL WITH NEAL M. LONKY, MD, MPH, MODERATOR (AUGUST 2010)

show me the data behind a panelist’s remarks!

I would be interested to know the specific data that support the following statement by Dr. Diane M. Harper in the roundtable on the human papillomavirus (HPV) vaccine (page 42):

Vaccine protection must last at least 15 years to reduce the rate of cervical cancer. Otherwise, the development of cervical cancer will only be postponed, if boosters are not implemented. It is now widely recognized that Cervarix induces high antibody titers, offering 100% efficacy even after 8.4 years, making it very likely that the protection it provides will continue for at least 15 years. It is also widely acknowledged by immunologists that Gardasil-induced titers for HPV 6, 11, and 18 are much shorter-lived, so protection is likely to wane 5 to 10 years after vaccination. That means that Gardasil provides excellent protection against one cancer-causing type of HPV. In addition, it protects against genital warts caused by HPV types 6 and 11 for at least 5 years. In comparison, Cervarix protects against five cancer-causing types of HPV, thereby preventing about 90% of cervical cancers, and is likely to remain effective for at least 15 years. There are 10 times as many women who have an abnormal Pap test as there are women who have genital warts, so one would think that Cervarix would be the vaccine of choice in preventing the life-threatening disease of cervical cancer.

I would like to disclose that I was a clinical investigator for Merck’s Future III trial, and I have served as a speaker for Merck in regard to Gardasil.

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